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Biomedical subjects

E Rocchi

Publications and source records attributed to E Rocchi.

51 records · Page 3Linked to original sources
PubMedDate not supplied

Acute intermittent porphyria: heterogeneity of mutations in the hydroxymethylbilane synthase gene in Italy.

Acute intermittent porphyria (AIP) is an autosomal disorder caused by molecular abnormalities in the gene coding for hydroxymethylbilane synthase (HMBS), the third enzyme in the heme biosynthetic pathway. So far, more than 170 different mutations responsible for AIP have been identified worldwide in the HMBS gene. In this study we have performed molecular characterization in 14 patients with suspected diagnosis of AIP and in 29 family members of Italian ancestry. Molecular analysis of the HMBS gene allowed us to identify 13 different mutations among 14 patients with reduced HMBS activity: 5 splicing defects (IVS9+22 G>A, 612 G>T, IVS11-2 delA, IVS12+2 T>C, and IVS13-1 G>A), 1 small insertion (182 insGA), 1 small deletion (730-731 delCT), and 6 missense/nonsense mutations (76 C>T, 295 G>A, 331 G>A, 580 C>T, 673 C>T, and 874 C>T), resulting in single-amino-acid substitutions or protein truncations. Six of these molecular abnormalities had already been described and 7 are new findings. In a previous work on an Italian population we detected 7 different mutations among 8 AIP patients. This study has raised to 18 the number of different mutations so far found among the Italian AIP population, 11 of which are new findings. We can conclude that the mutation screening in the Italian population contributes to improvement of the diagnostic approach of AIP and to establishing possible clustering of mutations in the Mediterranean area.

Adolescent↗
PubMedDate not supplied

Faecal and urinary coproporphyrin isomers in biliary atresia and neonatal hepatitis.

Based on the assumption that faecal and urinary coproporphyrin excretion is closely dependent on biliary function, coproporphyrin excretion was investigated in severe cholestatic diseases in infants and adults. The following subjects were investigated: biliary atresia (5), neonatal hepatitis (3), normal infants (11), adults with biliary obstruction (5) and normal adults (18). Urinary and faecal coproporphyrin concentrations were determined by solvent partition methods, and the isomers (I and III) were separated by thin-layer chromatography with direct spectrofluorometric scanning. The results showed a significant increase in urinary coproporphyrin in biliary atresia and neonatal hepatitis and in adults with biliary obstruction. All the cholestatic diseases showed the same marked increase in urinary isomer I. In biliary atresia and neonatal hepatitis there was a significant decrease in faecal coproporphyrin and a concomitant increase in isomer III (of bacterial origin) which was related to the extent of the biliary defect. Determination of urinary and faecal coproporphyrin, and particularly of the isomer distribution, may be a sensitive tool for diagnosis.

Adult↗
PubMedDate not supplied

Safety of valproate in porphyria cutanea tarda.

Treatment of epileptic seizures in patients with hepatic porphyrias is a challenging problem due to enzymatic induction activity of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and clonazepam (CZP). We present the case of a patient with partial seizures treated with PHT and showing clinical signs and biochemical abnormalities of porphyria cutanea tarda (PCT). We withdrew PHT and treated the patient with sodium valproate (VPA). We followed the patient for 6 months during VPA therapy. During this period, clinical signs of PCT disappeared and biochemical values normalized. Our study shows that VPA is a safe treatment in epileptic patients with PCT.

Aged↗
PubMedDate not supplied

Standard or branched-chain amino acid infusions as short-term nutritional support in liver cirrhosis?

The metabolic effects of selected and branched-chain amino acid (BCAA)-enriched parenteral solutions were studied in liver cirrhosis. After 3 days of an oral protein-free diet with balanced amino acid (AA) infusion, 36 cirrhotic patients without encephalopathy were randomly divided into four groups. Groups A and B were infused for 5 days with BCAA (valine, leucine, isoleucine) at doses of 0.5 and 1.0 g/kg/day, respectively, as the only nitrogen source. Group C received 0.8 g/kg of essential and nonessential AA solution with a prevalence of BCAA; the last group (D) continued the basic standard diet, as control. Routine chemistry, urinary nitrogen losses, nitrogen balance, and the whole plasma AA pattern were detected before and after the treatment period. BCAA alone led to an impressive and significant improvement in the basic AA pattern in both the A and B groups. The same results were obtained in group C for plasma AA. In particular, the ratio of BCAA to aromatic amino acids in groups A, B, and C was significantly increased (p less than 0.01, less than 0.02, less than 0.02, respectively). In group D the AA pattern and the BCAA/aromatic amino acid ratio remained unchanged. The negative nitrogen balance of the base state remained unchanged after 0.5 g of BCAA (A); it improved significantly and became positive during and after the infusions of a double dose of BCAA (B), as it did in the case of selective solutions (C), although to a lesser extent; the negative nitrogen balance of the control group showed only a slight improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMedDate not supplied

Multiwavelength videomicrofluorometric study of cytotoxic properties of a marine peptide, didemnin B, using adriamycin as reference compound.

Didemnin B (DB), a marine natural product, has very encouraging biological activity in vitro (Antineoplastic, immunosuppressive, antiviral). To learn more about its intracellular effects and targets, videomicrofluorometry on single living cells and a protocol of multiple labeling: Hoechst 342 for nuclear DNA, Rhodamine 123 for mitochondria and Nile Red for plasma membrane, have been used. DB behaves differently from Adriamycin, inducing at its IC50 dose of (20 nM) an accumulation of the CEM-WT lymphoblasts in the S phase of the cell cycle while we observed a 50% decrease of the mitochondrial labeling by R123, showing a decrease of the mitochondrial energetic state. Cytostatic dose of DB (250 nM) confirms these observations. However the treatment with a dose reported as apoptotic (1000 nM) induces a much faster effect (corresponding to that of 72 hours at the IC50 dose), 24 hours incubation induced a drastic decrease of nuclear DNA content as well as of the mitochondria energetic state. The evolution of NAD(P)H cellular content exhibited an increase that seems to indicate that the decrease of mitochondrial energetic state was dependent on inhibition of the mitochondrial activity due to an effect of DB at the mitochondrial level, either direct or mediated. Furthermore, the decrease of mitochondrial labeling appears as a very early event in the mechanisms leading to apoptosis.

Apoptosis↗
PubMedDate not supplied

Multiwavelength videomicrofluorometric study of cytotoxic effects of a marine peptide, didemnin B, on normal and MDR resistant CCRF-CEM cell lines.

The development of multidrug resistance (MDR) in heterogeneous cell sensitive and resistant populations to a variety of clinically important cytotoxic drugs poses a major obstacle to cancer chemotherapy. Didemnin B, a marine cyclic depsipeptide, displays interesting biological properties: antiviral activity, inhibition of DNA, RNA and protein synthesis, initiation of apoptosis and ability to block the cell cycle. As very little is known about its mode of action, we studied the effect of increasing doses of Didemnin B on sensitive and resistant human leukemic lymphoblast cell lines. The fluorescence of living cells simultaneously stained with Hoechst 33,342, Rhodamine 123 and Nile Red, were analyzed in a multiparametric approach involving multiwavelength microfluorometry. High concentrations of Didemnin B induced, in the sensitive cell line, a very early decrease in the energetic state of the mitochondria that occurs before a significant decrease of nuclear DNA content, observed simultaneously on sensitive and resistant cells, that could be related to an apoptosis process. Furthermore low Didemnin doses (50 nM) affected CEM-WT and CEM VLB differently, while higher doses (200 nM-250 nM and over) affected the two cell lines in the same way. This indicated that, at these doses, the membranar Pgp has no effect on the mode of action of Didemnin, suggesting that Didemnin does not need to be internalized to be active.

Antineoplastic Agents↗
PubMedDate not supplied

Selective amono acid solutions in hepatic encephalopathy treatment (a preliminary report).

Hepatic encephalopathy may complicate chronic liver diseases and portosystemic shunting. Recently it has been suggested that a change in the blood amino acid pattern (with elevated phenylalanine, tyrosine, methionine and depressed branched chain amino acids) and increased levels of octopamine and phenylethanolamine (a false neurotransmitter) are related causally to neurological symptoms. Previous works have suggested that an amino acid mixture of special formulation (enriched in branched chain amino acids and poor in aromatic amino acids) can normalize the plasma amino acid levels and consequently improve the neurological state. In order to test the actual therapeutic effect of these specially formulated solutions, the following therapeutic protocols were administered to 3 groups of cirrhotic patients: group 1 (15 cases): lactulose; group 2 (8 cases): special amino acid solutions; group 3 (8 cases): special amino acid solutions and lactulose. Clinical, laboratory and EEG examinations in a preliminary experiment, before and after treatment, showed that the best effect was obtained by the combined treatment with amino acid solutions and lactulose.

Adult↗
PubMedDate not supplied

Multiwavelength videomicrofluorometric study of some human leukemic lymphoblasts: effect of adriamycin on some biological parameter.

The development of multidrug resistance (MDR) in heterogeneous cell sensitive and resistant populations to a variety of clinically important cytotoxic drugs poses a major obstacle to cancer chemotherapy. The MDR phenotype is characterized by a decrease the intracellular drug accumulation and by an overexpression of the MDR1 gene which encodes the membrane protein, P-glycoprotein (Pgp). To evaluate the MDR phenotype, rationale investigations of the cytotoxic processes and effect,s of Adriamycin (ADR) were done to obtain information on individual cells. Such information could be obtained through a multiparametric approach involving multiwavelength microfluorometry and numerical image analysis on single living cells. To achieve this, cells should be simultaneously stained with Hoechst 33342 (nuclear staining), Rhodamine 123 (mitochondria staining) and Nile Red (cell contour delineation). Changes in the biological parameters accessible from R123, Ho33342 and C-SNARF-1/AM (probe used for the pHi measurements) labelling were found more informative than changes in morphological parameters for the discrimination of sensitive and resistant cells. Furthermore, this approach allows the discrimination between two resistant cell lines expressing different mechanisms of resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗