[Hyperhomocysteinemia in chronic renal failure.]. / L'iperomocisteinemia nell'insufficienza renale cronica: aspetti clinici, nutrizionali e tossicità.

Chronic renal failure (CRF) is frequently associated with increased plasma levels of homocysteine (Hcy), an amino acid that can be considered a new uremic toxin according to recent evidence. Studies on Hcy described first homocystinuria, an inherited disease characterized by high plasma Hcy levels and premature cardiovascular disease, resulting in high mortal-ity rates. Hyperhomocysteinemia was then shown to be associated with cardiovascular events both in the general population and in CRF patients. Hcy is a sulfur amino acid derived from dietary methionine, an essential amino acid. Methionine is condensed with ATP to form S-adenosylmethionine (AdoMet), the universal methyl donor in transmethylation reactions. The AdoMet demethylated product is S-adenosylhomocysteine (AdoHcy), which is the direct precursor of Hcy in vivo. Hcy is toxic for the endothelium, it enhances vascular smooth muscle cell proliferation, increases platelet aggregation, and acts on the coagulation cascade and fibrinolysis. Several mechanisms have been discussed to explain Hcy toxicity. Hcy levels increase as renal function declines and progresses to ESRD; the causes of hyperhomocysteinemia are still unclear. Studies in humans show that renal metabolic extraction depends on renal plasma flow; in addition, an alteration of the extrarenal metabolic clearance, depending on uremic toxins, may occur. Among the consequences of hyperhomocysteinemia in renal failure are: impaired protein methylation, with altered protein repair processes; DNA hypomethylation, with an alteration in the allelic expression of genes regulated through methylation; and protein homocysteinylation. Further, this review is dealing with the 'reverse epidemiology' issue, outlining also the main Hcy-lowering strategies.

Increased plasma protein homocysteinylation in hemodialysis patients.

Hyperhomocysteinemia, an independent cardiovascular risk factor, is present in the majority of hemodialysis patients. Among the postulated mechanisms of toxicity, protein homocysteinylation is potentially able to cause significant alterations in protein function. Protein homocysteinylation occurs through various mechanisms, among which is the post-translational acylation of free amino groups (protein-N-homocysteinylation, mediated by homocysteine (Hcy) thiolactone). Another type of protein homocysteinylation occurs through the formation of a covalent -S-S- bond, found primarily with cysteine residues (protein-S-homocysteinylation). Scant data are available in the literature regarding the extent to which alterations in protein homocysteinylation are present in uremic patients on hemodialysis, and the effects of folate treatment are not known. Protein homocysteinylation was measured in a group of hemodialysis patients (n=28) compared to controls (n=14), with a new method combining protein reduction, gel filtration and Hcy derivatization. Chemical hydrolysis was performed, followed by high-pressure liquid chromatography separation. The effects of folate treatment on protein homocysteinylation, as well as in vitro binding characteristics were evaluated. Plasma Hcy, protein-N-homocysteinylation and protein-S-homocysteinylation were significantly higher in patients vs controls. Plasma Hcy and protein-S-homocysteinylation were significantly correlated. After 2 months of oral folate treatment, protein-N-homocysteinylation was normalized, and protein-S-homocysteinylation was significantly reduced. Studies on albumin-binding capacity after in vitro homocysteinylation show that homocysteinylated albumin is significantly altered at the diazepam-binding site. In conclusion, increased protein homocysteinylation is present in hemodialysis patients, with possible consequences in terms of protein function. This alteration can be partially reversed after folate treatment.

[Renal stone ileus in xanthogranulomatous pyelonephritis. A case report]. / Occlusione intestinale da calcolo renale in pielonefrite xantogranulomatosa. Descrizione di un caso.

A peculiar case of intestinal occlusion caused by a renal stone in a patient with nephroduodenal fistula due to previous xanthogranulomatous pyelonephritis is reported. Only few cases of nephroduodenal fistula are described in the literature, generally as a single case report or in small series. A nephroduodenal fistula as a result of chronic renal inflammatory disease such as xanthogranulomatous pyelonephritis, is usually associated with renal stones, recurrent urinary tract infections or endocrine disorders. Finally, renal stone as a cause of ileus is an event rarely described in the literature. In the case described, a correct preoperative diagnosis was possible with computerized tomography. During the operation a big renal stone was found and removed from the small bowel, but a limited resection was necessary because of the vascular impairment of the tract. At 8-month follow-up from operation, the patient was in good health, and no symptoms of renal or intestinal diseases were found.

Expression of the retinoblastoma-related p107 and Rb2/p130 genes in human placenta: an immunohistochemical study.

It has been proposed that tumor suppressor genes may have a role in the mechanisms of proliferation and differentiation during human placental development. The Retinoblastoma gene family is a well known family of tumor suppressor genes. Many studies have pointed out a role of this family not only in cell cycle progression, but also during development and differentiation. On the light of these observations we have investigated the immunohistochemical expression pattern of the Retinoblastoma family members, p107 and Rb2/p130 in human placenta samples in first trimester and full-term placental sections. p107 and pRb2/p130 showed the most abundant expression levels during the first trimester of gestation and progressively declined to being barely detectable in the placenta by late gestation. These results indicate that the expression of the above genes is modulated during placental development and suggest a mechanism for controlling trophoblast proliferation.

Alteration of the Bcl-2:Bax ratio in the placenta as pregnancy proceeds.

The placenta is the primary site of nutrient and gas exchange between mother and foetus. During human placental development, proliferation, differentiation and apoptosis occur at different stages. In order to clarify some of the molecular mechanisms underlying these events, we investigated the pattern of expression of two members of the Bcl-2 family in human placenta samples and compared them to the level of apoptosis detected by the TUNEL method. In particular, we evaluated the expression of Bcl-2 and Bax and their ratio during the first and third trimester. We found that Bcl-2 was generally expressed at low levels during the entire gestational period. On the other hand, Bax was low during the first trimester but increased towards the end of gestation. In accordance with the change of ratio of these two molecules, the increase of apoptotic cells was observable in the third trimester. These data indicate that Bcl-2 and Bax are spatio-temporally regulated during placental development and that the different expression of the above mentioned genes is at least in part responsible for the delicate balance between cell proliferation and programmed cell death in the human placenta during pregnancy.

[Piezoelectric extracorporeal lithotripsy in ambulatory care]. / Litotricia extracorpórea piezoeléctrica en régimen ambulatorio.

The surgical approach for stone disease has completely changed during the last decade. Since 1980, ESWL and Endourology (percutaneous nephrolithotomy, ureteroscopy) have been used worldwide in the treatment of nephrolithiasis and today open surgery is necessary only in less than 5% of the cases. The second generation Wolf Piezolith 2300 is a lithotripter for the painless treatment of the majority of renal and ureteral stones. Treatment of stone patients on an out patient basis in a private clinic commenced in 1988 because of the low complications and side effects related to its use. We report the records of the first 70 patients treated in this way and controlled for at least 3 months after the treatment.