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Biomedical subjects

E Russo

Publications and source records attributed to E Russo.

At least 19 recordsLinked to original sources

Discontinuation of imatinib therapy after achievement of complete molecular response in a Ph(+) CML patient treated while in long lasting complete cytogenetic remission (CCR) induced by interferon.

Imatinib has become the gold standard therapy for Ph(+) CML, as it induces complete cytogenetic remission (CCR) in 75-90% of patients in chronic phase (CP), and up to 40% of these patients obtain at least a 3 log reduction of BCR/ABL transcript [Kantarjian HM, Cortes JE, O'Brien S, Luthra R, Giles F, Verstovsek S, et al. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. Blood. 2004;104:1979-1988]. However, it is not yet stated whether continued therapy is required to maintain this response or whether imatinib may be discontinued after confirmation of a prolonged complete molecular remission (CMR). We here report on a Ph(+) CML case in long lasting CCR following interferon-alpha treatment (IFN) which reached CMR with imatinib but soon relapsed at molecular level after this latter drug discontinuation; we considered the present observation also in the light of previously reported data.

Adenocarcinoma↗

Meiotic spindle presence and oocyte morphology do not predict clinical ICSI outcomes: a study of 967 transferred embryos.

With a view to correlating oocyte morphology and meiotic spindle presence to clinical intracytoplasmic sperm injection (ICSI) outcomes, 967 oocytes that led to 967 transferred embryos in 404 embryo transfers were studied. No relationship was found between oocyte morphology (ooplasm texture, perivitelline space largeness, perivitelline space granulation absence/presence and the first polar body shape) or meiotic spindle presence or absence and clinical pregnancy per transfer and implantation rates after ICSI. It was concluded that oocyte morphology and meiotic spindle presence or absence can only predict fertilization, cleavage rates and embryo quality, as previously described in the literature, but do not help in daily ICSI practice in the choice of the metaphase II oocyte that will lead to the embryo that starts clinical pregnancy.

Adult↗

Comparison of in-vitro outcomes from cryopreserved oocytes and sibling fresh oocytes.

In Italy, the restrictive IVF law generalizes the indication for oocyte freezing for surplus oocytes in 78.5% of in-vitro assisted reproductive cycles. With a view to understanding better what the prospects for intracytoplasmic sperm injection (ICSI) on frozen-thawed oocytes might be, the consequences of freeze-thaw procedures on fertilization, cleavage rates and embryo quality obtained from frozen-thawed oocytes were studied and compared with the results obtained from sibling fresh oocytes. Eleven IVF and 29 ICSI on 76 and 169 fresh oocytes were performed and the corresponding 40 ICSI on 221 sibling frozen-thawed oocytes. There was no difference in terms of fertilization rate between fresh and sibling frozen-thawed oocytes. The cleavage rate (98.0 and 94.4% with fresh oocytes in IVF and ICSI; 77.3% with frozen-thawed oocytes in ICSI; P < 0.001) and embryo quality (grade I embryos over total embryos: 36.7 and 22.2% with fresh oocytes in IVF and ICSI; 12.1% with frozen-thawed oocytes in ICSI; respectively P < 0.001 and P < 0.05) were statistically lower after oocyte cryopreservation. The significant decrease in meiotic spindle retrieval rate before freezing (62.4%) and after thawing procedures (43.4%; P < 0.001) suggests that cryoconservation induces irreversible damage to microtubule repolymerization. The consequences of oocyte cryopreservation procedures on embryo development are reviewed.

Adult↗

Preparation and evaluation of a chitosan salt-poloxamer 407 based matrix for buccal drug delivery.

The aim of this work was to prepare and evaluate a matrix for buccal drug delivery composed of a chitosan salt and poloxamer 407. Different chitosan salts were formed by reacting chitosan with acetic, citric, and lactic acid. Various proportions of poloxamer 407 were added to the aqueous solution of chitosan salt, and the residue obtained by lyophilisation was compressed into discs, using a 30 kN compression force. An experimental design (3(2)) was used to study the influence of the type of chitosan salt and of the relative amount of poloxamer on drug release capacity, swelling, erosion, and mucoadhesiveness of matrices. The results showed that matrix properties depended significantly on both relative amount of poloxamer and chitosan salt type. The rank orders of chitosan salts for the four processes evaluated were as follows: drug release: chitosan acetate>chitosan citrate>chitosan lactate; swelling: chitosan lactate>chitosan acetate=chitosan citrate; erosion: chitosan citrate>chitosan lactate>chitosan acetate; mucoadhesion: chitosan lactate>chitosan acetate=chitosan citrate. Mucoadhesion was particularly favoured when poloxamer 407 was present at about 30% (w/w). The matrix composed of chitosan lactate and poloxamer 407 showed the best characteristics for buccal administration.

Administration, Buccal↗

Early and tardive skin adverse events in chronic myeloid leukaemia patients treated with imatinib.

Imatinib related non-haematological side-effects are reported in <10% of chronic myeloid leukaemia patients and include oedema, weight gain, nausea, vomiting and muscle cramps. Cutaneous reactions are well-recognized events occurring mostly in patients treated at doses of 600 mg/d and higher, either in stable or progressive disease. We report on our experience relating to dermatological toxicities in imatinib treated CML patients showing a spectrum of skin reactions ranging from rashes to cutaneous carcinoma.

Adult↗

Effects of piracetam alone and in combination with antiepileptic drugs in rodent seizure models.

The nootropic drug piracetam was investigated in various experimental models of epilepsy. Generally, piracetam exhibits no or only moderate anticonvulsant properties against generalized tonic or clonic seizures. However, in many cases it did increase the anticonvulsant effectiveness of conventional antiepileptics, as shown in the maximal electroshock seizure (MES) threshold test, the traditional MES test or in DBA/2 mice. A pharmacokinetic interaction does not seem to be responsible for this effect. In lethargic mice, a model of absence seizures, piracetam significantly decreased the incidence and duration of spike-wave discharges. Furthermore, in the cobalt-induced focal epilepsy model piracetam reduced the number of spikes/min and in the hippocampal stimulation model it increased the anticonvulsant potency of phenobarbital and phenytoin after single and repeated administration. In conclusion, the well tolerated piracetam itself did not show marked anticonvulsant effects in most screening tests, however, its co-medication with antiepileptic drugs improved seizure protection in various models which may bear potential clinical significance.

Action Potentials↗

Molecular interactions of ruthenium complexes in isolated mammalian nuclei and cytotoxicity on V79 cells in culture.

In this paper, the molecular interactions in isolated mammalian nuclei of three ruthenium complexes, which are putative antineoplastic chemotherapeutic agents effective in reducing metastatic tumours in vivo, have been investigated and compared with the well-known antitumour drug CDDP (cis-diamminedichloroplatinum). The compounds studied are: Natrans-RuCl4(DMSO)Imidazole (NAMI), Natrans-RuCl4(DMSO)Oxazole (NAOX) and Natrans-RuCl4(TMSO)- Isoquinoline (TEQU). This study shows that the drugs bind to DNA but induce few, if any, DNA interstrand crosslinks, which are considered as the main biological lesions involved in the cytotoxic activity of several already known antitumour drugs, whilst in the same experimental conditions, CDDP is confirmed to induce them. On the other hand, proteins appear to be an important target in the cell for these drugs, since proteins-DNA crosslinks are shown to be induced by the complexes. Moreover, we investigated Ru complexes for their direct cytotoxicity on V79 cells in culture, showing that two of them (NAMI and NAOX) do not significantly reduce the cloning efficiency of the cells even at concentrations as high as 2-3 mg/ml: only TEQU both reduces cloning efficiency and induces a significant number of mutants in V79 cells in culture.

Animals↗

Development and in vitro evaluation of buccoadhesive tablets using a new model substrate for bioadhesion measures: the eggshell membrane.

For oral delivery of antimicrobial and anti-inflammatory drug, mucoadhesive tablets based on gelatin/hydroxypropylcellulose (HPC), gelatin/hydroxypropylmethyl-cellulose (HPMC), and gelatin/sodium carboxymethylcellulose (NaCMC) at different ratios were prepared by direct compression of the mixed powders. Metronidazole and benzydamine were used as model drugs. The in vitro bioadhesive properties, evaluated by a commercial tensile tester, were significantly affected by the model substrate employed, that is, a polypropylene (PP) membrane or a biological membrane (eggshell membrane). The use of the biological substrate seemed to supply more reliable data. All studied formulations showed an erosion-diffusion mechanism of release, anomalous or non-Fickian release, in agreement with the behavior of the swellable systems.

Administration, Oral↗

Expression of ADP-ribosyltransferase on normal T lymphocytes and effects of nicotinamide adenine dinucleotide on their function.

ADP-ribosyltransferase (ADPRT) is a glycosylphosphatidylinositol-anchored cell surface enzyme on CTL. Expression of this enzyme correlates with suppression of CTL functions in the presence of its substrate beta-nicotinamide adenine dinucleotide (NAD). To investigate the immunoregulatory importance of ADPRT on normal lymphocytes in vivo, NAD was injected into mice and the effects on cell-mediated and humoral immunity were assessed. Induction of both delayed-type hypersensitivity and CTL, but not Ab responses, are shown to be suppressed by NAD. Consistent with this, mature T cells, but not B cells or macrophages, express ADPRT and are able to ADP-ribosylate cell surface proteins. ADP-ribosylated molecules were identified as LFA-1, CD8, CD27, CD43, CD44, and CD45. Concomitant to ADP-ribosylation of these molecules, T cell trafficking to secondary lymphoid organs is suppressed by NAD. To examine whether this is due to effects of NAD on cell activation, Ag-stimulated responses were assayed in vitro. NAD is shown to inhibit induction of cell proliferation, cytotoxicity, and cytokine secretion. It is suggested that ADPRT regulates T cells on the level of transmembrane signaling via ADP-ribosylation of cell surface molecules. This effect is reported to be indirect, as it involves transmission of signals through TCRs, which are not ADP-ribosylated.

Animals↗

Cannabis for migraine treatment: the once and future prescription? An historical and scientific review.

Cannabis, or Marijuana, has been used for centuries for both symptomatic and prophylactic treatment of migraine. It was highly esteemed as a headache remedy by the most prominent physicians of the age between 1874 and 1942, remaining part of the Western pharmacopoeia for this indication even into the mid-twentieth century. Current ethnobotanical and anecdotal references continue to refer to its efficacy for this malady, while biochemical studies of THC and anandamide have provided a scientific basis for such treatment. The author believes that controlled clinical trials of Cannabis in acute migraine treatment are warranted.

Cannabis↗

Effects of caffeine on glucose tolerance: a placebo-controlled study.

OBJECTIVE: The investigation was performed to study the effects of 200 mg oral caffeine on glucose tolerance. DESIGN: Single-blind Latin square with active treatment (caffeine) and placebo. SETTING: The University of Padova, Department of Internal Medicine. SUBJECTS: 30 nonsmoking healthy subjects aged 26-32 years who abstained not only from coffee but also from tea, chocolate and cola for 4 weeks and who had given their informed consent. INTERVENTIONS: A 75 g oral glucose tolerance test (OGTT) was performed after giving caffeine or placebo (highly decaffeinated coffee). RESULTS: The glycaemic curve was normal in all subjects and was similar in the two groups until the second hour; in subjects taking caffeine a shift towards the right was detected at the 2nd, 3rd and 4th hours in comparison to those taking the placebo. Blood insulin levels were comparable after caffeine and after placebo along the entire OGTT. CONCLUSIONS: The data suggest that caffeine intake induces a rise in blood glucose levels that is insulin independent.

Adult↗

Ursodeoxycholate promotes protein phosphorylation in the cytosol of rat hepatocytes.

A study is presented of the effect of the bile salt ursodeoxycholate (UDC) on protein phosphorylation by [gamma-32P]ATP in the cytosol from rat hepatocytes. Gel electrophoresis and corresponding autoradiograms of cytosolic proteins show that UDC promotes phosphorylation of at least eight different protein bands. Four of them (the 36, 60, 64 and 76 kDa) are phosphorylated by Ca2+ and phospholipid-dependent protein kinase (PKC); three (the 31, 51 and 71 kDa) are phosphorylated by cAMP-dependent protein kinase (PKA) and one protein band, with molecular weight of 34 kDa, apparently contains substrates of both PKC and PKA. Data are reported indicating that UDC can directly affect the intrinsic activity of protein kinases.

Animals↗

Blood pressure, serum cholesterol and nutritional state in Tanzania and in the Amazon: comparison with an Italian population.

OBJECTIVE: To confirm that westernization of dietary habits represents a stimulus for the expression of cardiovascular risk. DESIGN: Three representative age- and sex-matched samples of general populations of three continents were compared cross-sectionally by analysis of variance. PARTICIPANTS: In total 1110 subjects aged 22-89 years, divided into three groups (370 from Tanzania and Uganda, 370 from the Amazonian region of Brazil, and 370 from northern Italy; 111 men and 259 women in each group). RESULTS: The blood pressure of Africans eating a low-salt fish and vegetable' diet was lower than those of Brazilians, whose diet was based on cereals and meat, and highly urbanized Italians. The systolic blood pressure was correlated to the body mass index for all three populations, but with age only for the Brazilians and Italians. The total cholesterol level and body mass index, both of which are low among Africans, increased progressively with increasing economic level. CONCLUSIONS: Transition from a rural to an urbanized lifestyle is accompanied by a rise in the main cardiovascular risk factors; the present data also show that environmental rather than racial factors have a crucial impact on the risk pattern of populations.

Adult↗

Oxidative phosphorylation and F(O)F(1) ATP synthase activity of human hepatocellular carcinoma.

A study of mitochondrial oxidative phosphorylation in biopsies from human hepatocellular carcinoma is presented. Tumour mitochondria as compared to control liver mitochondria, besides a reduced activity of complex IV (cytochrome c oxidase) of the respiratory chain, show a decreased phosphorylative capacity. This appears to be mainly related to a defective F o F(1) ATP synthase complex. Use of an antibody against the F(1) portion of the complex demonstrate a definite decrease for the beta subunit of F(1) in tumour mitochondria.

Adenosine Triphosphatases↗

DNA damage and topoisomerase II inhibition induced by a benzopsoralen derivative.

The ability of 4-hydroxymethyl-4',5'-benzopsoralen (HMBP) to damage DNA of Chinese hamster ovary cells (CHO) and to inhibit the activity of topoisomerase II in vitro has been studied. This compound is characterized by a fourth ring condensed at the furan-side in the psoralen molecule. Contrary to other known furocoumarin derivatives, HMBP induces chromosomal aberrations in mammalian cells without UVA activation. The lesions induced in the dark by HMBP in DNA were studied by alkaline and neutral elution in CHO cells; comparable amounts of single-strand breaks and DNA-protein cross-links as well as the formation of double-strand breaks were detected. Moreover, HMBP appeared to inhibit the activity of mammalian topoisomerase II in vitro, in both the catenation and the decatenation assay. In these experiments the drug was effective only when it was pre-incubated with DNA substrate. These results are also consistent with the cytotoxic and mutagenic activity of HMBP in the dark, as tested on V79 Chinese hamster cells (V79/HGPRT system).

Animals↗

HLA-A, B, C and DR in hepatitis B virus (HBV)-related liver cirrhosis: a study of 851 elderly subjects.

The possible correlation between HLA system and liver cirrhosis secondary to HBV infection has been studied in 102 hospitalized elderly patients affected by liver cirrhosis (histologically proven) and 749 elderly health controls. Increased frequencies of HLA-A2, Cw4, Cw5, DR4, DR5 and DR7 have been observed in patients with liver cirrhosis and previous HBV infection, while a lower frequency of HLA-A2 and higher frequencies of HLA-A3, B35, Cw4, DR3 have been observed in patients without previous HBV infection when compared with controls.

Aged↗

[An epidemiological study of breast-feeding practice in the referral population of USSL 46 "Alto Mantovano", the Lombardy region. Unità di servizio screening locale].

The aim of this study is to assess the prevalence of breast feeding in the children population of familial advisory bureau in our territory, the reasons for the choice of this kind of nutrition and its duration. The authors also researched if there is some relationship between the choice of feeding and the kind of parturition, mother age, her education and job. The possible influence of the preparatory course of childbirth attendance, mass media and family on this choice was researched to complete the study.

Adolescent↗