Biomedical subjects
Publications and source records attributed to Giovanni Poli.
[Structure: see text] Palladium-catalyzed arylation of sulfenate anions generated from beta-sulfinyl esters can take place under biphasic conditions. This hitherto unknown reaction provides a simple, mild, and efficient route to aryl sulfoxides in good yields. The development of a new pseudo-domino type I procedure involving a sulfinylation followed by a Mirozoki-Heck coupling is also described.
Palladium-catalyzed allylic alkylation of sulfenate anions, generated from beta-sulfinylesters by retro-Michael reaction, can take place under biphasic conditions. This new reaction provides a simple, mild, and efficient route to allyl sulfoxides in good yields.
Considerable attention has been focused on definition and enhancement of the analytical quality in laboratory testing over the past decades. Advances in laboratory technology and computer informatics have allowed a major sense of confidence with the analytical phase and more efforts should now be focused on extra-analytical areas of improvement, that should further strengthen the link between cost effectiveness and clinical outcome. Deduction and implementation of common reference intervals, to be possibly shared by a regional network of clinical laboratories, appear so far a crucial step to increase efficiency and harmonization. With the experience gained from External Quality Control exercises and with the consensus of several contributory laboratories, this process is underway in Italy. Quality performances resulting from widespread implementation of common reference intervals and longitudinal comparison of patient's data, will allow clinical laboratories to accomplish with a major transferability, amplifying health benefits and meeting increasing health systems demand.
We screened 134 consecutive patients with von Willebrand disease (VWD) (106 type 1, 26 type 2, and 2 type 3 VWD) for the most important inherited prothrombotic risk factors. One hundred eight patients (80.6%) were positive for at least one of the prothrombotic risk factors screened for. A high prevalence of prothrombin G20210A (10.5%) and factor V Leiden (11.9%) mutations was found with allele frequencies of 5.2 and 6%, respectively. Three carriers of multiple prothrombotic gene mutations experienced a thrombotic event. Our study suggests that the recent evidence of an association between inherited thrombotic and hemorrhagic disorders also holds true in VWD patients.
Oral anticoagulant therapy has been widely employed to prevent and treat a variety of thrombotic disorders, although a new generation of antithrombotic drugs, which offer inhibition of clot-bound as well as fluid-phase thrombin, has been developed and tested in several clinical trials. Although most anticoagulant responses to hydroxycoumarin compounds are well established, there are controversial evidences on their influence on activated factor VII (FVIIa). After analyzing the prothrombin time (PT) (International Normalized Ratio reference range, 0.92-1.08), factor VII clotting activity (FVII:C) (reference range, 75-130 U/dl) and activated factor VII clotting activity (FVIIa:C) (reference range, 30-110 U/l) in 46 consecutive patients on stable warfarin therapy for atrial fibrillation, a consistent trend towards decreased values of both FVII:C and FVIIa:C was observed as PT values increased. At moderate-intensity anticoagulation, with international normalized ratios between 2 and 3, the mean activities of FVII:C and FVIIa:C dropped to 28 U/dl (range, 9-61 U/dl) and 5.8 U/l (range, 1-18 U/l), respectively. Results of our investigations indicate that warfarin therapy decreases FVIIa:C, highlighting the potential benefits of oral anticoagulants in thrombotic disorders and other clinical conditions characterized by increased levels of FVIIa. Owing to the good correlation with FVIIa:C, we also hypothesize that the PT and/or FVII:C might be employed for monitoring recombinant FVIIa therapy.
Poor standardization of preanalytic variables exerts a strong influence on the reliability of coagulation testing, consuming valuable health care resources and compromising patient outcome. Most uncertainties emerge from patient misidentification and the procedures for specimen collection and handling. Location of unsuitable venous access or problematic phlebotomies may produce spurious activation of the hemostatic system and hemolytic specimens. Prolonged venous stasis is associated with hemoconcentration and spurious variations of most coagulation assays. Additional pitfalls can be introduced by inappropriate phlebotomy tools and small-gauge needles. Inappropriate filling and mixing of the tube, unsuitable procedures for centrifugation and storage of the specimens are additional aspects that need accurate standardization. Besides traditional preanalytic variables affecting routine coagulation testing, thrombin-generation assays require specific criteria to be accurately fulfilled. These aspects include the type of specimen (platelet-poor plasma, platelet-rich plasma or whole blood), blood collection tubes, storage conditions and the presence of residual platelets. Compliance with new international quality assessment programs, which will also involve coagulation laboratories, encompasses the adoption of suitable strategies for reducing undue variability throughout the whole testing process. Such strategies would not entail extraordinary costs and are affordable with a structured outlay of existing resources, educational policies and compliance with reliable guidelines.
The phlebotomy technique, particularly the use of small-bore needles, may influence the reliability of coagulation testing and platelet count. Routine coagulation tests were assayed in blood specimens collected from 22 consecutive patients in three separate, sequential phlebotomies, using butterfly devices with different needle sizes. Test results of samples collected with 23 and 25 G needles were compared with those obtained with the currently recommended 21 G needle. Although both the prothrombin time and activated partial thromboplastin time displayed a trend towards lower values employing the smaller 23 and 25 G needles, results did not differ significantly from the reference 21 G needle specimen, with the exceptions of D-dimer (25 G versus 21 G needle, 186 +/- 70 versus 178 +/- 66/ml, P < 0.01) and platelet count (23 G versus 21 G needle, 246 +/- 55 versus 254 +/- 56 x 10(-3)/l, P < 0.01; 25 G versus 21 G needle, 240 +/- 55 versus 254 +/- 56 x 10(-3)/l, P < 0.01). None of the mean biases recorded for the parameters was clinically meaningful, nor did they exceed the current desirable analytical quality specifications for desirable bias. Results of the present investigation suggest that, when a proper technique is used and within certain limitations, butterfly devices with small-bore needles may be a reliable alternative to draw venous blood for platelet count and coagulation testing.
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[reaction: see text] Palladium-catalyzed intramolecular allylic alkylations of unsaturated EWG-activated amides can take place under phase-transfer conditions or in the presence of a crown ether. These new reaction conditions are milder and higher yielding than those previously reported. A rationalization for such an unexpected result is put forth and validated by DFT-B3LYP calculations. The results suggest cyclization via a counterion-free (E)-enolate TS.
The association of lymphoid neoplasms and antiphospolipid antibodies (APA), with or without thromboembolic complications, has been reported in several cases. We describe one case of B-cell non-Hodgkinís lymphoma (NHL) in which the combination of rituximab with standard chemotherapy led to the complete remission of a severe hypercoagulable state associated with APA.
A new aza analogue of epiisopicropodophyllin (the C-3 epimer of podophyllotoxin) has been synthesized exploiting two original strategic steps. Rings A/B and E are entered at an early stage via a cationic benzhydrylation process. A palladium-catalyzed pseudo-domino (Pd-PDOM) intramolecular process generates rings C/D in a single synthetic operation.
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A novel palladium(0)-catalyzed cyclization to 3,4-disubstituted pyrrolidin-2-ones has been developed. The new approach relies upon the concomitant generation of stabilized acetamide enolate anions and of a pi-allyl-palladium appendage, properly tethered by a nitrogen atom. Reaction conditions have been optimized for the methoxycarbonyl-stabilized model reaction [(Z)-2 --> 3] and then applied to other substrates. A broad range of acetamide anion stabilizers was shown to allow the desired intramolecular C-C bond formation (MeO(2)C, MeCO, NC, (EtO)(2)PO, PhSO(2)). The cyclizations gave exclusively 5-exo-trig ring closure, thereby affording gamma-lactams. All the cyclizations gave the corresponding 3,4-disubstituted pyrrolidin-2-ones with total diastereoselection. Complete trans preference was unequivocally demonstrated for the model reaction via a NOESY experiment.
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