New rifamycins. II. Synthesis and biological activity of oximes, hydrazones, and semicarbazones of 3-N-(piperidin-4-one)rifamycin S.
Explore the source record for details and available documents.
Bacteria↗
Biomedical subjects
L Marsili
Publications and source records attributed to L Marsili.
New rifamycins modified at positions 3 and 4. Synthesis, structure and biological evaluation.
A number of semisynthetic rifamycin derivatives modified at positions 3 and/or 4, belonging to general structures 3, 5, and 6 (see Scheme 1), have been prepared. The synthesis, structure and antimicrobial evaluation of the new compounds are described. All the derivatives have "in vitro" antibacterial activities well comparable with that of rifampicin.
Bacteria↗
Biological activity of a new class of rifamycins. Spiro-piperidyl-rifamycins.
The biological properties of spiro-piperidyl-rifamycins, a new class of rifamycin antibiotics, are described. In these derivatives the positions 3 and 4 have been incorporated into an imidazolyl ring bearing a spiro-piperidyl group N substituted with linear and branched aliphatic chains. The in vitro antibacterial activity against Staphylococcus aureus and Mycobacterium tuberculosis increases with the number of the carbon atoms in the linera side chain, whereas the inhibitory effect on Escherichia coli is lowered. The antibacterial activity is only marginally affected by branching of the side chain. In vivo (experimental infections of mice) the optimal therapeutic activity against M. tuberculosis is shown by compounds bearing 3 approximately 5 carbon atoms as a linear or branched side chain; in comparison with rifampicin, the potency of these derivatives is 2 approximately 3 times higher. The finding is in a good agreement with the exceptional tissue tropism, which seems to be a favourable property of this group of derivatives.
Animals↗
Stress MR imaging for evaluation of popliteal artery entrapment.
The popliteal artery entrapment (PAE) syndrome has been recognized as a cause of arterial occlusion in young people. It is the result of an anomaly of the relationship between the popliteal artery and the gastrocnemius muscle. Eight young health volunteers (16 legs) and six patients (10 legs) with suspected PAE underwent magnetic resonance (MR) imaging. Gradient-echo images were obtained in axial planes with the leg at rest and during active plantar flexion against resistance. Imaging at rest allowed identification of PAE signs in only one leg, which had an anomalous medial course of the popliteal artery. In the other cases, only the stress technique was able to show signal loss in the popliteal artery due to muscular compression (two legs) or the presence of accessory muscle slip around the vessel (two legs), as confirmed at surgery. MR imaging is therefore a useful technique for the diagnosis of PAE because of its capability of combining information obtainable with other modalities.
Adult↗
Postsurgical follow-up of aortic dissections by MRI.
Fifteen patients with surgical repair for dissecting aneurysm were examined by Magnetic Resonance Imaging (MRI), using a 0.5 T super-conductive unit. Follow-up studies were obtained at 1 to 18 months (mean 7.2) post-surgery. T1-weighted spin-echo sequences were acquired with ECG gating on axial, coronal and oblique sagittal planes. In 6 patients gated gradient rephased sequences were also employed. Residual intimal tear in the native aorta was visualized in 11 patients, together with new or progressive extention of the dissection and aneurysmatic development. Gradient rephasing sequences were useful in detecting slow flow and thrombotic deposits and in evaluating relations to aortic vessels and intimal flap. MR images provided useful information on pathology allowing a non invasive evaluation of the status of the aorta.
Adult↗
Skin biopsy of Mediterranean cetaceans for the investigation of interspecies susceptibility to xenobiotic contaminants.
Various studies on Mediterranean cetaceans have revealed bioaccumulation of contaminants such as organochlorines (OCs) and heavy metals. The susceptibility of these animals to organic pollutants and the relationship between bioaccumulation and population decline (as in the case of Delphinus delphis) are unexplored fields. In this study, we used a non-destructive approach (skin biopsy) to explore OC bioaccumulation processes and mixed-function oxidase activity (BPMO) in four species of cetaceans: striped dolphin (Stenella coeruleoalba), bottlenose dolphin (Tursiops truncatus), common dolphin (D. delphis) and fin whale (Balaenoptera physalus). Significant differences in BPMO induction and OC levels were found between odontocetes and mysticetes, the former having mixed-function oxidase activities four times higher than the latter, binding with levels of OCs one order of magnitude higher in odontocetes. A significant correlation (P < 0.05) between BPMO activities and OC levels was found in B. physalus. In an ongoing project, fibroblast cultures have been used as an alternative in vitro method of evaluating interspecies susceptibility to contaminants such as OCs and polycyclic aromatic hydrocarbons (PAHs). These results suggest that cetacean skin biopsies are a powerful non-invasive tool for assessing ecotoxicological risk to Mediterranean marine mammals species.
Animals↗
Skin biopsies for cell cultures from Mediterranean free-ranging cetaceans.
The aim of this study was to develop a useful method for obtaining viable tissue samples for establishing cell cultures from skin biopsies of free-ranging cetaceans. The skin biopsies were performed by two methods: dart from an air gun and dart from a crossbow. The dart tip was modified to collect tissue. The tissue was kept in tissue culture medium at ambient temperature, then processed within 24 h. Many modifications in culture technique, with respect to conventional culture methods for human fibroblasts, were made. The cultures thus obtained can be used for many purposes, including genetic and toxicological studies. In toxicology they are an alternative in vitro system for studying threatened animals such as marine mammals. In particular, fibroblasts can be used to test the vulnerability of cetaceans and pinnipeds to different environmental contaminants such as organochlorine compounds, heavy metals and polycyclic aromatic hydrocarbons.
Animals↗
The use of porphyrins as a non-destructive biomarker of exposure to contaminants in two sea lion populations.
This study was carried out in two populations of Otariaflavescens, living in a polluted and in a reference site, in order to validate the use of porphyrins as a non-destructive biomarker of exposure to environmental contaminants. Analysis of porphyrins was carried out in the feces, blood and fur of free ranging sea lions and in the liver and kidney of stranded specimens. The results show that: (a) all biological materials used were useful for porphyrin determinations; (b) no clear seasonal variations in porphyrin accumulation and excretion were found; (c) differences in fecal porphyrin levels existed between the two colonies.
Animals↗
Multi-trial biomarker approach in Meganyctiphanes norvegica: a potential early indicator of health status of the Mediterranean "whale sanctuary.".
The aim of this study was to propose a suite of biomarkers (BPMO activity, NADPH-cytocrome c reductase, NADH-ferricyanide reductase. esterases, porphyrins, vitellogenin and zona radiata proteins) and residue levels (organochlorines, PAHs and heavy metals) in the zooplanktonic euphausiid Meganyctiphanes norvegica as a potential multi-disciplinary diagnostic tool for assessment of the health status of the Mediterranean "whale sanctuary". Very little difference in BPMO was detected between sites, with values ranging from 0.75 to 2.68 U.A.F./mg prot/h. On the other hand larger differences between sites were found for reductase activities. Esterases (AChE), porphyrins (Copro-, Uro-, Proto-porphyrins) vitellogenin and zona radiata proteins were also detectable in this zooplanctonic species. Hg showed mean levels of 0.141 ppm d.w., Cd 0.119 ppm d.w. and Pb 0.496 ppm d.w. Total PAHs ranged from 860.7 to 5,037.9 ng/g d.w., carcinogenic PAHs from 40.3 to 141.7 ng/g d.w., HCB from 3.5 to 11.6 ng/g d.w., DDTs from 45.3 to 163.2 ng/g d.w. and the PCBs from 84.6 to 210.2 ng/g d.w.
Animals↗
Biomarkers for endocrine disruptors in three species of Mediterranean large pelagic fish.
The hypothesis that Mediterranean top predator species, such as large pelagic fish, are potentially at risk due to endocrine disrupting chemicals (EDCs), is investigated. The potential estrogenic effects of PHAHs in three fish species of commercial interest, the top predators bluefin tuna (Thunnus thynnus thynnus), swordfish (Xiphias gladius), and Mediterranean spearfish (Tetrapturus belone), were investigated using vitellogenin (Vtg), zona radiata proteins (Zrp) and mixed function oxidases (EROD, BPMO) as diagnostic tools. High induction of Vtg and Zrp was detected by western blot and ELISA techniques in adult males of X. gladius and T. thynnus thynnus, suggesting that these species are at high toxicological risk in the Mediterranean sea. Comparison of BPMO and EROD activities in the three species indicated, both in male and female, much higher MFO activity in bluefin tuna. This data suggests high exposure of this species to lipophilic xenobiotic contaminants in the Mediterranean environment.
Animals↗
MR characterization of hepatic lesions by t-null inversion recovery sequence.
Tissue characterization of focal hepatic lesions was performed employing an inversion recovery sequence with short repetition time and short inversion time (TI) values. Different and specific TI values, correlated to the in vivo measured T1 relaxation times, were used to null the signal intensity of each type of lesion. In 40 patients studied, we observed the nulling effect of normal liver in 10 of 10 cases with a TI of 136 ms, of metastases in 7 of 8 cases with a TI of 175 ms, of hemangiomas in 15 of 16 cases with a TI of 200 ms, and of cysts in 6 of 7 cases with a TI of 235 ms. A quantitative analysis of the nulled signal was performed by measuring the signal/noise values. A further qualitative and quantitative characterization was carried out by evaluating the signal intensity of hepatic lesions at the null point of normal liver. The method provided the possibility of discriminating different focal lesions with specificity values of 83-94%, according to the type of lesion.
Adult↗
Pre-operative angiography in gastric cancer surgery with extended lymphadenectomy.
BACKGROUND/AIMS: The value of pre-operative angiographic evaluation in patients undergoing gastric cancer surgery with extended lymphadenectomy was assessed in a prospective study comparing exposed and unexposed groups of patients. METHODOLOGY: During the period from July 1991 to October 1997, 76 patients (Group A--exposed) were pre-operatively submitted to a digital subtraction angiography (DSA) after informed consent. Concurrently, 94 patients (Group B--unexposed) were included as an unexposed reference group. All patients underwent total or subtotal gastrectomy with D2 lymphadenectomy according to the guidelines proposed by the Japanese Research Society for Gastric Cancer (JRSGC). RESULTS: In 34 (45%) exposed patients (Group A), DSA detected an atypical vascular anatomy. Major anatomical variations of the celiac axis, its branches and the superior mesenteric artery were discovered in 4 subjects (5%). Vascular anomalies affecting the surgical tactics of lymphadenectomy were detected in less than 8% of patients. Five post-operative deaths (6.6%) were registered between patients of the Group A, exposed to pre-operative angiography, 8 in the unexposed Group B (8.5%). Post-operative morbidity was significantly higher (P = 0.038) in the Group B (34%) in comparison to Group A (20%) but no difference in risk of individual complications was detected. CONCLUSIONS: Although useful in the presence of major vascular anomalies, it appears that pre-operative angiography did not significantly reduce intra- and post-operative complications associated with radical gastrectomy combined with extended lymphadenectomy. Arteriography is therefore not routinely recommendable but its use is mandatory in specific operations for gastric cancer.
Aged↗
Stop-flow in mediastinum and thorax for resistant lymphoma.
BACKGROUND/AIMS: Management of patients with heavily pretreated malignant lymphoma failing frontline treatment and salvage high-dose chemotherapy and autologous peripheral stem cell rescue, is problematic. A pilot study was conducted to evaluate isolated thoracic perfusion of drugs by means of stopflow technique. METHODOLOGY: Six patients were enrolled in the study; diagnoses included 4 advanced Hodgkin's disease, 1 primary mediastinal B-cell lymphoma, and 1 anaplastic large cell lymphoma. Patients were aged 18-37 years; 4 presented with bulky mediastinum. They had never achieved a complete response since all had progressed from front-line treatment, and 3 had even failed salvage high-dose chemotherapy with autologous peripheral stem cell rescue. Cisplatin (100 mg/m2) and melphalan (35 mg/m2) were used. Carmustine (100 mg/m2) were added to these 2 drugs and cytarabine (2000 mg/m2) in patients not previously treated by carmustine, etoposide, cytarabine, and melphalan. Epidoxorubicin (70 mg/m2) was added in patients who previously received a suboptimal dosage of antracycline. Drugs were delivered monthly via aortic perfusion performed by means of Aigner's stop-flow technique. RESULTS: Overall 13 cycles of perfusional chemotherapy were administered with a median number of 2 cycles. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery. After 1 month, 6 (100%) objective responses after isolated thoracic perfusion were recorded, 3 (50%) of which were complete. Tolerance to therapy was excellent. Hematological toxicity was mild and transfusional support was needed only in one course. At the last follow-up, 2 patients are alive (1 complete response and 1 very good partial response, maintained). CONCLUSIONS: This new therapeutical approach seems very active in recurrent/refractory malignant lymphoma and may play an important role in this setting.
Adolescent↗
[MR-angiography with contrast bolus vs digital angiography in peripheral arterial occlusive disease of the legs].
PURPOSE: Aim of our study was to compare MR Angiography and Digital Angiography in the diagnosis of peripheral vascular occlusive disease. MATERIAL AND METHODS: Forty-five patients underwent both MRA and DSA examination of the peripheral arterial district. We employed a 1.5 Tesla MRI unit using 3D FSPGR T1-w sequence on coronal scan plane (TR=5.2 ms; TE=1.5 ms; slice=1.5/3 mm; FOV=48 cm; matrix 384x512; TA=16/24 s), before and after automatic iv injection of Gd-DTPA BMA (0.15/0.3 mmol/kg) with a flow rate of 2 ml/s. We evaluated the vascular district from renal to medio-distal tibial arteries. The acquisition of this arterial district required a semi-automatic movement of the examination table. Qualitative and quantitative analyses were carried out according to MIP reconstructions. DSA evaluation, considered as the gold standard, was performed by trans-femoral access using a 4-5F catheter. RESULTS: The MRA examination detected 246 steno-occlusive lesions while 285 were identified with DSA. No statistically significant differences were found among the various degrees of stenotic lesions detected by the two METHODS. The MRA examination had specificity and sensitivity values of: 100% and 84,8% for the iliac axes; 98,9% and 94,3% for the femoral district; 100% and 84,9% for the popliteal district; 97% and 89% for tibial vessels. CONCLUSIONS: MRA showed a high diagnostic accuracy close to that of DSA. On the basis of our short experience we believe that MRA will be a useful method in the detection of various degrees of peripheral artery occlusive diseases reserving DSA for the therapeutical step.
Aged↗
[Isolation regional perfusion].
Explore the source record for details and available documents.
Carcinoma, Non-Small-Cell Lung↗