Quantitative structure-activity relationships of mutagenic and carcinogenic aromatic amines.
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Journal Article↗
Biomedical subjects
A Giuliani
Publications and source records attributed to A Giuliani.
Deriving a quantitative chirality measure from molecular similarity indices.
A versatile new method has been developed as a continuous symmetry measure for chiral compounds. The application of principal component analysis (PCA) to the complete N x N pairwise similarity matrices (electrostatic potential and shape indices) of a series of dihydropyridine calcium channel antagonists allowed to single out a chirality component and to compute a chirality score in terms of the between-enantiomers difference on the component value. The possibility to have chirality defined continuously at the series level could be of importance in eudismic analyses where the relative potency of two enantiomers is studied as well as in QSAR studies dealing with chiral molecules in order to improve the power of the generated models.
Calcium Channel Blockers↗
[Hormone replacement therapy with a transdermal estradiol gel and oral micronized progesterone. Effect on menopausal symptoms and lipid metabolism].
In a multicenter observational study, the efficacy and acceptance of two different regimens of postmenopausal hormone replacement therapy in the form of a combination of 17 beta-estradiol in percutaneous gel application and micronized oral progesterone were evaluated. Forty-eight patients (aged 40-66 years) received 2.5 g estradiol gel plus either continuously micronized progesterone 100 per day (group A) or, sequentially, 200 mg per day between day 16 and 25 of a monthly cycle (group B) for two months. A significant reduction in typical menopausal symptoms, especially vasomotor complaints like hot flushes or sweating, was observed in both groups (score average at the beginning for hot flushes: 2.0 in group A and 1.8 in group B; after two months of treatment, 0.7 in group A and 0.4 in group B). Cholesterol levels were slightly reduced but statistically significant (235.9 +/- 49.55 mg/dl vs. 226.3 +/- 52.24 mg/dl; p < 0.05) only in group A; a trend towards lower cholesterol was observed in group B (236.5 +/- 47.82 mg/dl vs. 227.4 +/- 44.72 mg/dl). Lipoprotein (a) was also significantly reduced in group A (32.57 +/- 36.52 mg/dl vs. 28.28 +/- 31.03 mg/dl in group A; 31.7 +/- 28.42 mg/dl vs. 28.34 +/- 23.71 in group B; p < 0.05). The overall acceptance of this therapy was excellent or good in 91.3% of group A and 92.8% of group B patients.
Administration, Cutaneous↗
Exogenous administration of L-arginine protects cholinergic neurons from colchicine neurotoxicity.
The effect of L-arginine administration on susceptibility/resistance of NO-producing neurons was investigated in non-ischemic neurodegenerative conditions. ChAT mRNA level was measured by in situ hybridization in the basal forebrain after i.c.v. colchicine administration. Colchicine induced down-regulation of ChAT mRNA level followed by degeneration of cholinergic neurons. L-Arginine treatment increased ChAT mRNA level and prevented/delayed ChAT mRNA decrease by colchicine. These data suggest that L-arginine treatment may protect cholinergic neurons from colchicine-induced degeneration.
Animals↗
Protective effects of Mangifera indica L. extract, mangiferin and selected antioxidants against TPA-induced biomolecules oxidation and peritoneal macrophage activation in mice.
We compared the protective abilities of Mangifera indica L. stem bark extract (Vimang) 50-250 mgkg(-1), mangiferin 50 mgkg(-1), vitamin C 100 mgkg(-1), vitamin E 100 mgkg(-1)and beta -carotene 50 mgkg(-1)against the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative damage in serum, liver, brain as well as in the hyper-production of reactive oxygen species (ROS) by peritoneal macrophages. The treatment of mice with Vimang, vitamin E and mangiferin reduced the TPA-induced production of ROS by the peritoneal macrophages by 70, 17 and 44%, respectively. Similarly, the H(2)O(2)levels were reduced by 55-73, 37 and 40%, respectively, when compared to the control group. The TPA-induced sulfhydryl group loss in liver homogenates was attenuated by all the tested antioxidants. Vimang, mangiferin, vitamin C plus E and beta -carotene decreased TPA-induced DNA fragmentation by 46-52, 35, 42 and 17%, respectively, in hepatic tissues, and by 29-34, 22, 41 and 17%, in brain tissues. Similar results were observed in respect to lipid peroxidation in serum, in hepatic mitochondria and microsomes, and in brain homogenate supernatants. Vimang exhibited a dose-dependent inhibition of TPA-induced biomolecule oxidation and of H(2)O(2)production by peritoneal macrophages. Even if Vimang, as well as other antioxidants, provided significant protection against TPA-induced oxidative damage, the former lead to better protection when compared with the other antioxidants at the used doses. Furthermore, the results indicated that Vimang is bioavailable for some vital target organs, including liver and brain tissues, peritoneal exudate cells and serum. Therefore, we conclude that Vimang could be useful to prevent the production of ROS and the oxidative tissue damages in vivo.
Animals↗
Randomized, controlled trial to compare the J-pouch and W-pouch configurations for ulcerative colitis in the maturation period.
PURPOSE: Proctocolectomy with ileal pouch-anal anastomosis has become the procedure of choice for the treatment of ulcerative colitis. Functional results may differ with different pouch designs. This randomized study aimed to evaluate the relative effectiveness of two-limb J and four-limb W reservoir designs in the so-called maturation period after ileostomy closure. METHODS: Twenty-four patients underwent ileal pouch-anal anastomosis for ulcerative colitis. Eleven were randomly assigned to the J-pouch group and 13 to the W-pouch group. Frequency of defecation and other functional data were collected at 4, 8, and 12 months after ileostomy closure. Maximum tolerated volume was assessed in the same period by a latex balloon inflated with water. Maximum resting anal pressure, maximum voluntary contraction, and the rectoanal inhibitory reflex were assessed in the preoperative period and at 4, 8, and 12 months after ileostomy closure. RESULTS: Frequency of defecation decreased from 4 to 12 months after ileostomy closure in both groups (P = 0.04), but patients with a W-pouch had significantly lower values than patients with J-pouches (P < 0.01). Night-time defecation (P = 0.04) and use of antidiarrheals (P = 0.04) were significantly lower for patients with a W-pouch. Maximum tolerated volume was greater in the W-pouch group throughout the whole period (P = 0.01). Maximum resting anal pressure, maximum voluntary contraction, and rectoanal inhibitory reflex did not differ between the study arms. CONCLUSION: Patients with W-pouch have better functional results than those with J-pouches in the "maturation period" after ileostomy closure.
Adult↗
Nonlinear methods in the analysis of protein sequences: a case study in rubredoxins.
Two computational methods widely used in time series analysis were applied to protein sequences, and their ability to derive structural information not directly accessible through classical sequence comparisons methods was assessed. The primary structures of 19 rubredoxins of both mesophilic and thermophilic bacteria, coded with hydrophobicity values of amino acid residues, were considered as time series and were analyzed by 1) recurrence quantification analysis and 2) spectral analysis of the sequence major eigenfunctions. The results of the two methods agreed to a large extent and generated a classification consistent with known 3D structural characteristics of the studied proteins. This classification separated in a clearcut manner a thermophilic protein from mesophilic proteins. The classification of primary structures given by the two dynamical methods was demonstrated to be basically different from classification stemming from classical sequence homology metrics. Moreover, on a more detailed scale, the method was able to discriminate between thermophilic and mesophilic proteins from a set of chimeric sequences generated from the mixing of a mesophilic (Rubr Clopa) and a thermophilic (Rubr Pyrfu) protein. Overall, our results point to a new way of looking at protein sequence comparisons.
Amino Acid Sequence↗
Low fetal oxygen saturation at birth and acidosis.
OBJECTIVE: To measure umbilical cord blood oxygen saturation, to calculate preductal oxygen saturation at birth, and to assess its predictive value for acidosis. METHODS: Umbilical cord blood samples of 1537 live-born singleton neonates were analyzed. Oxygen saturation was measured by spectrophotometry; pH and base excess were measured by a pH and blood gas analyzer. Preductal oxygen saturation was calculated with an empirical equation. Acidosis was defined as 2 standard deviations (SDs) below the mean of umbilical artery (UA) pH or base excess (7.09 and -10.50 mmol/L, respectively). The predictive value for acidosis of UA and umbilical vein (UV) oxygen saturation and calculated preductal oxygen saturation was determined with receiver operating characteristic curves. RESULTS: The mean values (+/-SD) of UV, UA, and calculated preductal oxygen saturation were 52 +/- 18%, 26 +/- 17%, and 31 +/- 16%, respectively. Forty-seven neonates had UA pH less than 7.09 and 60 had UA base excess less than -10.50 mmol/L. The UV, UA, and calculated preductal oxygen saturation showed considerably weaker relations to UA base excess (multiple r(2) =.056,.003, and.017, respectively; P <.001) than to UA pH (multiple r(2) =.112,.126, and.148, respectively; P <. 001). Receiver operating characteristic areas under the curve were higher when predicting low pH compared with low base excess (for UV, UA, and calculated preductal oxygen saturation: 0.716 versus 0.699, 0.747 versus 0.586, and 0.765 versus 0.628, respectively). The difference was significant for UA oxygen saturation (P <.05). All tests showed high sensitivity and negative predictive values, but low specificity and positive predictive values. CONCLUSION: Low fetal oxygen saturation measured at birth seemed to be associated with low fetal pH and base excess values, but its predictive value for acidosis in an unselected population was limited, particularly if acidosis was metabolic.
Acidosis↗
Mapping protein sequence spaces by recurrence quantification analysis: a case study on chimeric structures.
Recurrence quantification analysis (RQA) was used to characterize the folding properties of 22 chimeric sequences derived from two parent proteins of similar length but different three-dimensional arrangement. A non-linear relation between sequence data and their RQA representation was revealed, which points to new information carried by this method as compared with classical best-alignment methods. This new information is significantly correlated with the folding properties of the hybrid polypeptide chains, as substantiated by careful statistical analysis of the recurrence plots' numerical descriptors, thus encouraging their systematic use to complement sequence data in both proteomics and protein engineering tasks. Even the direct visual screening of the qualitative graphical features of recurrence plots is shown to provide useful hints to discriminate between different recurrence structures of protein sequences.
Amino Acid Sequence↗
The role of hydrophobicity patterns in prion folding as revealed by recurrence quantification analysis of primary structure.
It has been suggested that the number and strength of local contacts are the major factors governing conformation accessibility of model two ground-state polypeptide chains. This phenomenology has been posed as a possible factor influencing prion folding. To test this conjecture, recurrence quantification analysis was applied to two model 36mers, and the Syrian hamster prion protein. A unique divergence of the radius function for the recurrence quantification variable %DET of hydrophobicity patterns was observed for both 36mers, and in a critical region of the hamster prion protein. This divergence suggests a partition between strong short- and long-range hydrophobicity patterns, and may be an important factor in prion phenomenology, along with other global thermodynamic factors.
Algorithms↗
The cultural heritage shapes the pattern of tumour profiles in Europe: a correlation study.
STUDY OBJECTIVE: This study investigates the spatial pattern of tumours in Europe to check the feasibility of a large scale ecological epidemiology approach to cancer in Europe. SETTING: The tumour types relative frequencies and cancer incidence (for men and women) reported in the European cancer registries were investigated by exploratory data analysis techniques. Socioeconomical descriptors of the female condition were considered as well. MAIN RESULTS: The classification of the European regional areas covered by the cancer registries followed almost exactly the boundaries set by the long and intermingled European history in terms of life styles and cultural heritage. This result supports the notion of a predominant role of environmental factors in cancer induction. Further support to the above result was given by the finding of a correlation between differential male-female cancer incidence, and socioeconomic descriptors of the female condition. CONCLUSIONS: From a methodological point of view, the consistency of these results pointed to the feasibility of an ecological approach to tumour epidemiology.
Cultural Diversity↗
Revealing deterministic structures in click-evoked otoacoustic emissions.
Click-evoked otoacoustic emissions (CEOAEs) were studied by means of recurrence quantification analysis (RQA) and were found to be endowed with a relevant amount of deterministic structuring. Such a structure showed highly significant correlation with the clinical evaluation of the signal over a data set including 56 signals. Moreover, 1) one of the RQA variables, Trend, was very sensitive to phase transitions in the dynamical regime of CEOAEs, and 2) appropriate use of principal component analysis proved able to isolate the individual character of the studied signals. These results are of general interest for the study of auditory signal transduction and generation mechanisms.
Acoustic Stimulation↗
Separation of sperm and vaginal cells based on ploidy, MHC class I-, CD45-, and cytokeratin expression for enhancement of DNA typing after sexual assault.
BACKGROUND: Successful DNA typing after rape is limited when only a few sperm and numerous vaginal cells are recovered from a swab, resulting in an extremely unfavorable ratio of male to female DNA. The goal of this study was to develop a protocol involving sperm cell sorting with flow cytometry based on differences in ploidy, major histocompatibility (MHC) class I, CD45 and cytokeratin expression. METHODS: Vaginal lavages were mixed with serially diluted ejaculate. After immunostaining and stoichiometric nuclear staining, spermatocytes were isolated by fluorescence-activated cell sorting. All sorted cells were used for DNA extraction and subsequent quantitative fluorescent multiplex polymerase chain reaction. The preferential lysis was performed for comparison. RESULTS: The sorting procedure was superior to the preferential lysis method within all tested dilutions. One documented case of rape was examined with both procedures and only after cell sorting with flow cytometry was the male DNA identified. CONCLUSIONS: We were able to show that separation of sperm and vaginal cells using cell sorting with flow cytometry may be crucial when there is only a few sperm detectable after rape.
Cell Separation↗
Use of sphingolipid analogs: benefits and risks.
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Ceramides↗
Recurrence quantification analysis in molecular dynamics.
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Computer Simulation↗
Changing pattern of chronic hepatitis D in Southern Europe.
BACKGROUND & AIMS: The aim of this study was to assess changes in the clinical pattern of hepatitis D virus (HDV) infection in Italy, brought about by improved control of hepatitis B and D viruses, and to establish the natural history of chronic hepatitis D. METHODS: Histological diagnosis and clinical features of 122 patients with HDV recruited from 1987 to 1996 in three Italian tertiary referral centers (Torino, northern Italy; San Giovanni Rotondo and Castellana Grotte, southern Italy) were compared with those of 162 patients collected in the same centers in the previous decade. Patients from both groups with at least 6 months of follow-up were included in a new subgroup to assess the natural history of the disease. RESULTS: Among 162 patients referred from 1977 to 1986, 9 (6%) had mild hepatitis at histology vs. 9 (8%) of 122 patients referred in the second decade; 105 (65%) vs. 21 (17%) had severe hepatitis; 46 (28%) vs. 38 (31%) had histological asymptomatic cirrhosis; and 2 (1%) vs. 54 (44%) had clinically overt cirrhosis. For 159 patients (121 men and 38 women; mean age, 34 +/- 11), a follow-up of more than 6 months was documented, and they were included in the natural history subgroup. After 78 +/- 59 months of follow-up, 112 (70%) survived free of liver transplantation: 9 underwent transplantation, 32 died of liver failure, and 6 of acquired immunodeficiency syndrome. Estimated 5- and 10-year probability of survival free of orthotopic liver transplantation was 100% and 100% for patients with mild hepatitis, 90% and 90% for severe hepatitis, 81% and 58% for histological asymptomatic cirrhosis, and 49% and 40% for clinical cirrhosis (P < 0.01), respectively. CONCLUSIONS: Occurrence of fresh and severe forms of hepatitis D has diminished greatly in Italy. Contemporary patients represent cohorts infected years ago who survived the immediate medical impact of hepatitis D. The disease has been asymptomatic and nonprogressive in a minority; in the majority, it rapidly advanced to cirrhosis but thereafter subsided with stable clinical conditions for more than a decade.
Adult↗
Isolated splenic metastasis from endometrial carcinoma.
Splenic involvement by carcinomatous metastases occurs late in the course of widely disseminated disease. Solitary metastasis to the spleen from a primary of any source is an uncommon event. We report a case of a 58-year-old woman in which an asymptomatic solitary metastatic endometrial adenocarcinoma of the spleen was detected 28 months after resection of the primary malignancy and treated by splenectomy. There are thirteen other reported cases of solitary splenic metastasis from gynecological cancers; in four of these reports the source was endometrial.
Adenocarcinoma↗
31Phosphorus magnetic resonance spectroscopy to evaluate medical therapy efficacy in peripheral arterial disease. A pilot study.
BACKGROUND: Human and animal studies have shown that propionyl-L-carnitine, increasing carnitine content, improves the energy metabolism of ischemic skeletal muscle. The aim of the study was to evaluate the accuracy of Doppler continuous wave, Treadmill test and 31Phosphorus magnetic resonance spectroscopy in determining the efficacy of propionyl-L-carnitine in patients with peripheral arterial disease. METHODS EXPERIMENTAL DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Eighteen male patients with peripheral arterial disease (category 3) and 8 healthy volunteers form the basis of the study. Patients quit smoking, start physical training (2-3 Km walk per day) and were assigned to medical therapy consisting of propionyl-L-carnitine (8 patients) or placebo (10 patients). Patients were studied with Doppler continuous wave, Treadmill test and 31Phosphorus magnetic resonance spectroscopy at day 0 and at day 90. The following parameters were assessed by the principal component analysis: clinical (absolute claudication, ankle brachial index at rest and at 2, 5 and 10 minutes after completing Treadmill exercises) and biochemical (inorganic phosphorus/phosphocreatine ratio and pH profiles at 20% and 50% of the maximum load, the recovery half time of phosphocreatine, number of exercise steps and slope of linear relationship between muscle power and inorganic phosphorus/phosphocreatine ratio). RESULTS: Final evaluation showed a significant improvement of clinical and biochemical variables (p < 0.05 and p < 0.02 respectively). Breaking down the results on the basis of the two study arms, 31Phosphorus magnetic resonance spectroscopy showed a significant improvement of biochemical variables in the group of patients treated with propionyl-L-carnitine (p < 0.05) and was more sensitive in the evaluation of changes induced by 90-day treatment as compared with the other noninvasive examinations. CONCLUSIONS: 31P-MRS permits the evaluation of muscle metabolic effect induced by PLC after a 90-day-period in patients affected by category 3 of peripheral arterial disease and it is a more sensitive tool in the evaluation of the pharmacological effects of medical therapy.
Aged↗