DNA repair mechanisms involved in the removal of DBPDE-induced lesions leading to chromosomal alterations in CHO cells.

Polycyclic aromatic hydrocarbons (PAH) such as dibenzo[a,l]pyrene (DBP) are wide-spread environmental pollutants most probably mutagenic and carcinogenic to humans. Detailed data on the cytogenetic effects of anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DBPDE) in mammalian cells are not available in the literature. The aim of this study is to elucidate the mechanisms involved in the induction of chromosomal aberrations and sister chromatid exchanges (SCEs) by DBPDE in mammalian cells. In order to achieve this a parental (AA8) and different DNA repair-deficient Chinese hamster ovary cell lines such as UV4, UV5, UV61 (nucleotide excision repair, NER), EM9 (base excision repair, BER), irs1SF (homologous recombination repair, HRR) and V3-3 (non-homologous end joining, NHEJ) were used. The most sensitive cell lines for DBPDE-induced chromosome aberrations were EM9 and irs1SF, while EM9 and V3-3 cell lines were the most sensitive in terms of SCEs induction. It can be suggested that the BER pathway plays an important role in the repair of lesions induced by DBPDE, affecting both chromosomal aberrations and SCEs induction. Moreover, the HRR pathway seems to play a role in cellular resistance to DBPDE mainly in terms of chromosomal aberration induction while the NHEJ pathway takes part affecting only the induction of SCEs.

Distribution of UVC-induced chromosome aberrations along the X chromosome of TCR deficient and proficient Chinese hamster cell lines.

Cells with a transcription coupled repair (TCR) deficiency are characterized by a higher sensitivity to UVC irradiation and by an increase in apoptosis and chromosomal aberration frequencies. It has been claimed that the higher frequency of chromosomal aberrations results from the transcription blockage caused by UVC-lesions located in the transcribed strands of the genome. The distribution of chromosome breakpoints in euchromatic and heterochromatic regions of the X chromosome from TCR deficient and proficient Chinese hamster cell lines was studied. Most UVC-induced breakpoints occurred in euchromatic regions of the X chromosome in both cell lines. No increase of UVC-induced breakpoints in the euchromatic region of the UV61 X chromosome was observed, indicating that TCR failure alone cannot be responsible for the increased frequency of chromosomal aberrations. Differential chromatin remodeling in the TCR defective cell line is proposed as a possible mechanism involved in the distribution of UVC-induced breakpoints along the Chinese hamster X chromosome. A similar explanation for the increase of UVC-induced chromosomal aberrations in TCR defective cells is given.

Thyroid tissue remnants after "total thyroidectomy".

Total Thyroidectomy (TT) is a gold standard for benign bilateral pathologies and malignant pathologies of the thyroid. TT has numerous advantages over less radical approaches, such as the resolution of the thyroid pathology, avoidance of recurrences, and improved response to life-long substitutive organotherapy. TT has a negligible rate of recurrence. Near Total Thyroidectomy (NTT) is associated with a low rate of recurrence. Subtotal Thyroidectomy (ST), in which a portion of the thyroid gland is deliberately left in the thyroid lodge, has a considerably higher rate of recurrence. The incidence of complications with TT is similar to that with other techniques of thyroid exeresis. However, despite the radical intent of surgeons, a real TT is not always carried out. The complete removal of all the thyroid tissue employing TT is not the norm and micro/macroscopic remnants almost always remain. The literature on these tissue remnants is often based on techniques that are not very accurate in terms of determining the diameters of the tissue remaining. In our study, conducted by colour echo-doppler of the thyroid lodge in 102 patients who had undergone TT for benign thyroid pathologies, we demonstrated significant thyroid tissue remnants after TT in 34 cases of 102 (33,3%). Therefore, out of a total of 102 so-called "total thyroidectomies", only 68 (66,7%) were really total, whereas 12 patients (11,76%) had near total thyroidectomy, leaving tissue remnants < 1 cm, and 22 patients (21,57%) had subtotal thyroidectomy, with tissue remnants > or = 1 cm.

Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles.

Cycles with progesterone elevation during controlled ovarian stimulation (COS) for IVF/ICSI are commonly managed with a "freeze-all" strategy, due to a well-recognized detrimental effect of high progesterone levels on endometrial receptivity. However, also a detrimental effect of elevated progesterone on day-3 embryo quality has recently been found with regards to top quality embryo formation rate. Because blastocyst culture and cryopreservation are largely adopted, we deemed relevant to determine whether this detrimental effect is also seen on blastocyst quality on day 5-6. This issue was investigated through a large two-center retrospective study including 986 GnRH antagonist IVF/ICSI cycles and using top quality blastocyst formation rate as the main outcome. Results showed that on multivariate analysis sperm motility (p<0.01) and progesterone levels at ovulation triggering (p = 0.01) were the only two variables that significantly predicted top quality blastocyst formation rate after adjusting for relevant factors including female age, BMI, basal AMH and total dose of FSH used for COS. More specifically, progesterone levels at induction showed an inverse relation with top quality blastocyst formation (correlation coefficient B = -1.08, 95% CI -1.9 to -0.02) and ROC curve analysis identified P level >1.49 ng/ml as the best cut-off for identification of patients at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study is the first to investigate the top quality blastocyst formation rate in relation to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone is associated with lower rates of top quality blastocyst. Hence, the advantages of prolonging COS to maximize the number of collected oocytes might eventually be hindered by a decrease in top quality blastocysts available for transfer, if increasing progesterone levels are observed. This observation extends the results of two recent studies focused on day-3 embryos and deserves further research.

A bicyclo[3.2.0]hept-3-en-6-one approach to prostaglandin intermediates.

[reaction:see text] The substituted cyclopentanic structures, 6-benzyloxymethyl-7-hydroxy-2-oxabicyclo [3.3.0]octan-3-one (1), a Corey lactone derivative, and 6-exo-benzyloxymethyl-2-oxabicyclo[3.3. 0]oct-7-en-3-one (2), have been obtained stereoselectively through the bicyclo[3.2.0]hept-3-en-6-one approach via 5-benzyloxymethyl-3-hydroxy-6-heptenoic acid, easily accessible from the inexpensive monoprotected cis-2-butene-1,4-diol.

One-pot direct conversion of 2,3-epoxy alcohols into enantiomerically pure 4-hydroxy-4,5-dihydroisoxazole 2-oxides.

[structure: see text]. A new methodology for the one-pot direct conversion of 2,3-epoxy alcohols into enantiomerically pure 4-hydroxy-4,5-dihydroisoxazole 2-oxides 1 has been found. The reaction works at room temperature and can be run at the 5-10 g scale. The mixture of 4,5-cis and 4,5-trans isomers obtained can be separated as such or as the bis-TDS ethers. A preliminary example of reductive cleavage of 1 to the corresponding amino polyol is also reported.

Products, rate constants and mechanisms of gas-phase reactions of CX(3)(+), CX(2)(+), CX(+) (X = F and/or Cl) and Cl(+) with 1,1,1- and 1,1,2-trichlorotrifluoroethane.

The gas-phase ion chemistry of 1,1,1- and 1,1,2-trichlorotrifluoroethane was investigated with an ion trap mass spectrometer. Following electron ionization both compounds (M) fragment to [M - Cl](+), CX(3)(+), CX(2)(+), CX(+) (X = F and/or Cl) and Cl(+). The reactivity of each of these fragments towards their neutral precursors was studied to obtain product and kinetic data. Whereas [M - Cl](+), CCl(3)(+) and CCl(2)F(+) cations are unreactive under the experimental conditions used, all other species react via halide abstraction to give [M - Cl](+) and, to a far lesser extent, [M - F](+). In addition, CX(2)(+) ions form CClX(2)(+) in a process which formally amounts to chlorine atom abstraction, but more likely involves chloride ion abstraction followed by charge transfer. CX(+) ions also form minor amounts of CX(3)(+) product ions, possibly via chloride abstraction followed by or concerted with dihalocarbene elimination from the (incipient) [M - Cl](+) ion. Trivalent carbenium ions are less reactive than divalent species, which in turn are less reactive than the monovalent ions (reaction efficiencies are given in parentheses): CF(3)(+)(0.70) < CF(2)(+)(0.78) < CF(+)(0.96). More interestingly, within each family of ions reactivity increases with the number of fluorine substituents (e.g. CF(2)(+) > CFCl(+) > CCl(2)(+) and CF(+) > CCl(+)), i.e. reactivity increases with the ion thermochemical stability, as measured by available standard free enthalpies of formation. Evaluation of the energetics involved shows that reactions are largely driven by the stability of the neutrals more than of the ions. Finally, the products observed in the reaction of Cl(+) are attributed to ionization of the neutral via charge transfer and fragmentation.

Bifid ureter with blind-ending branch.

A patient with a blind-ending branch of bifid ureter, one of the rarest anomalies in the upper urinary tract, is described.

[Nutritional effect of pectin in swine during growth and before slaughter]. / Efecto nutricional de la pectina en cerdos en crecimiento y terminación.

The nutritional effects that the addition of 2 and 4% of citrus pectin produce on the pig, was investigated. Forty pigs were divided into two treatments and fed with and without pectin during the growth and finishing period. Dorsal back-fat thickness was measured in all pigs before slaughtering (103 +/- 1.5 kg). The addition of 2% of pectin in the growth period (41 to 70 kg live weight) produce a decrease of 6 and 3% in the daily weight gain and the feed conversion rate, respectively. The addition of 4% of pectin in the finishing period (71 to 103 kg live weight) induced a highly significant (p less than 0.01) increase of 125 g (15%) in the daily weight gain and equal feed conversion rate as compared to the control treatment. The average thickness of back-fat in pigs subjected to the pectin treatment was 2 mm (8%) less than in those of the control group. In conclusion, we may report that the addition of pectin during the finishing period produces an increase in the daily weight gain rate without affecting feed conversion. Besides, it decreases the back-fat thickness.

Is color-Doppler US a reliable method in the follow-up of transjugular intrahepatic portosystemic shunt (TIPS)?

Transjugular intrahepatic portosystemic shunt (TIPS) has become a widely accepted treatment for complications of portal hypertension. Shunt or hepatic vein stenoses or occlusions are common short- and mid-term complications of the procedure, with a one-year primary patency ranging from 25% to 66%. When promptly identified, shunt stenosis or occlusion may be treated before the recurrence of gastrointestinal bleeding or ascites. The revision is usually successful and the primary-assisted patency of TIPS is approximately 85% at one year.Doppler sonography is a widely accepted screening modality for TIPS patients, both as a routine follow-up in asymptomatic patients and in those cases with clinically suspected TIPS malfunction.In a routine US follow-up, a TIPS patient is scheduled for a control 24 h after the procedure, and then after one week, 1 month, 3 months, and at 3-month intervals thereafter. Venography is at present performed solely on the basis of a suspected shunt dysfunction during the sonographic examination.Color-Doppler sonography is the most reliable method for monitoring the shunt function after TIPS implantation. Several studies have shown that Doppler sonography is a sensitive and relatively specific way to detect shunt malfunction, particularly when multiple parameters are examined. Achieving high sensitivity is optimal so that malfunctioning shunts can be identified and shunt revision can be performed before symptomatic deterioration. Venous angiography is at present indicated only on the basis of US suspicion of shunt compromise. Power-Doppler US and US contrast media can be useful in particular conditions, but are not really fundamental.

SommarioLa derivazione portosistemica per via percutanea transgiugulare, nota con l'acronimo TIPS, è diventata una modalità di trattamento delle complicanze dell'ipertensione portale. Stenosi od occlusioni dello shunt o delle vene epatiche sono complicanze a breve e medio termine, con pervietà a un anno compresa tra 25% e 66%. Se la diagnosi di stenosi od occlusione è precoce, il trattamento consente di evitare recidiva di ematemesi o ascite. La revisione dello shunt è generalmente di successo e la pervietà assistita della TIPS è di circa il 5% a un anno.Le tecniche Doppler sono ampiamente accettate nelle procedure di screening dei pazienti con TIPS, sia nel paziente asintomatico sia in quello con sospetto clinico di malfunzione dello shunt. In una procedura di follow-up la valutazione color-Doppler viene eseguita dopo 24 ore, dopo 7 giorni, dopo 1 mese, dopo 3 mesi e quindi ogni 3 mesi. La venografia viene oramai effettuata soltanto su precisa indicazione dell'esame ecografico. Il color-Doppler è la metodica migliore per il monitoraggio del funzionamento dello shunt dopo l'impianto di una TIPS. Molti studi hanno dimostrato che il Doppler è sensibile e relativamente specifico nell'identificare la malfunzione dello shunt, particolarmente se molteplici parametri vengono esaminati contemporaneamente. L'elevata sensibilità consente di identificare gli shunt malfunzionanti indirizzandoli alla revisione prima del peggioramento delle condizioni. La venografia viene effettuata solo su indicazione della valutazione color- e power-Doppler. L'utilizzo del power-Doppler e del mezzo di contrasto può essere utile in particolari condizioni, ma non è realmente fondamentale.

Drug abuse and illicit trafficking in Italy: trends and countermeasures, 1979-1990.

The author begins with a discussion on trends in drug abuse and trafficking in Italy in the period 1979-1990, when the country was experiencing major heroin-related problems and the situation with regard to cocaine trafficking and abuse was rapidly deteriorating. He then describes the organization of the anti-drug services in Italy and identifies strategies pursued by the Italian Government with a view to intensifying its activities in international drug control.

Ischemic necrosis of proximal gastric remnant following subtotal gastrectomy with splenectomy.

Ischemic necrosis of the gastric remnant is a rare and serious complication of high subtotal gastrectomy, rarely of the distal resection of the stomach. The authors report one case after subtotal gastrectomy with splenectomy, review the literature about this subject, and suggest that in all procedures the surgeon must take full account of the variability of gastric blood flow. Conservative therapy of this complication with total parenteral nutrition is proposed.

Medium sized lactones with hypolipidaemic and antioxidant activity: synthesis and biological evaluation of promising dual-action anti-atherosclerosis drugs.

Macrocyclic lactones 1a-b have been synthesized and their potential therapeutic value evaluated. The key structural feature of these active 'chimera' compounds is the 12-membered lactone ring that brings together the well-known polysubstituted hydroquinone moiety of antioxidants and the alpha,alpha-dimethyl substituted acyl residue of gemfibrozil. Lactones 1a-b showed better activity than probucol, a classical phenolic antioxidant, in preventing the Cu++-induced oxidative modification of human LDL. The hypolipidaemic activity of the new lactones, evaluated as the inhibition of lipids biosynthesis in Hep-G2 cells, was comparable to that of gemfibrozil. These features, added to the lack of cytotoxicity, make this new class of medium sized lactones promising dual-action drugs useful as anti-atherosclerosis agents.