Biomedical subjects
Publications and source records attributed to A Leoni.
We report the synthesis of a new hybrid 13 which is a combination of the naturally occurring antitumor agent distamycin A 1 and the pyrrolo[2,1-c][1,4]benzodiazepine 11, related to the naturally occurring anthramycin 2. The antitumor activity of the hybrid 13 was tested in vitro and compared to the natural product distamycin 1 and the PBD 11.
We describe a case of transient neurological deficit that occurred after unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly injected through a 25-gauge pencil-point spinal needle. The surgery and anaesthesia were uneventful, but 3 days after surgery, the patient reported an area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on (loss of pinprick sensation) without reduction in muscular strength. Sensation in this area returned to normal over the following 2 weeks. Prospective multicentre studies with a large population and a long follow-up should be performed in order to evaluate the incidence of this unusual side effect. However, we suggest that a low solution concentration should be preferred for unilateral spinal anaesthesia with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection rate are employed), in order to minimize the risk of a localized high peak anaesthetic concentration, which might lead to a transient neurological deficit.
Axillary brachial plexus block using 20 mL of 0.75% ropivacaine or 2% mepivacaine was compared in a prospective, randomized, double-blind study of two groups of 15 patients. The times to onset of sensory and motor block and to resolution of motor block, as well as the time to onset and degree of post-operative pain were recorded by an observer blinded to the identity of drug. Times to onset of sensory block were similar in the two groups (ropivacaine 10 min, mepivacaine 8 min). Resolution of motor block in the operated hand and the time to first requirement of post-operative analgesia occurred later with ropivacaine (9 h 50 min and 10 h) than with mepivacaine (3 h 50 min and 6 h), P < 0.01 for both measurements. Nine patients who received ropivacaine and two patients who received mepivacaine did not require further post-operative analgesia (P < 0.05). Ropivacaine is less toxic than other long-acting local anaesthetics, and 0.75% ropivacaine may be better for brachial plexus block when fast onset is required and prolonged pain relief is useful.
We have evaluated the influence of speed of intrathecal injection on lateral distribution of 0.5% hyperbaric bupivacaine. We studied 60 patients undergoing lower limb surgery who were placed in the lateral position with the operative side in the dependent position. After dural puncture (25-gauge Whitacre spinal needle), the needle aperture was turned towards the dependent side and 0.5% hyperbaric bupivacaine 8 mg was injected randomly at a rate of 0.02 ml s-1 (group slow, n = 30) or 0.25 ml s-1 (group fast, n = 30). Lateral position was maintained for 15 min while a blinded observer recorded loss of pinprick sensation and degree of motor block on both surgical and non-surgical sides. There were no differences between the groups. Forty-five minutes after patients were turned to the supine position, spinal anaesthesia was unilateral in 17 patients in group slow (56%) and in 13 patients in group fast (43%). We conclude that using extremely low speeds for intrathecal injection were not clinically advantageous in obtaining unilateral spinal anaesthesia.
UNLABELLED: To evaluate the influence of needle type on the lateral distribution of 0.5% hyperbaric bupivacaine, 30 patients undergoing lower limb surgery were placed in the lateral position with the side to be operated on dependent and underwent dural puncture by either a 25-gauge Whitacre (n = 15) or a 25-gauge Quincke (n = 15) spinal needle. The needle hole was turned toward the dependent side and 8 mg of 0.5% hyperbaric bupivacaine was injected over 30 s. The lateral position was maintained for 15 min while a blind observer recorded loss of pinprick sensation and degree of motor block on both the dependent and nondependent sides every 5 min until regression of motor block by 1 degree on the dependent side. Thirty minutes after the patients were placed in the supine position, unilateral sensory block was observed in 10 patients in the Whitacre group (66%) and in 2 patients in the Quincke group (13%) (P < 0.05). No differences in the rate of unilateral motor block were observed (73% and 40% in Whitacre and Quincke groups, respectively). We conclude that when a small dose of 0.5% hyperbaric bupivacaine is injected slowly into patients in the lateral position for 15 min, the Whitacre spinal needle provides a more marked differential block of sensory nerve roots between dependent and nondependent sides compared with the Quincke needle. IMPLICATIONS: Because unilateral spinal anesthesia can be advantageous for lower limb surgery, we evaluated the influence of the Whitacre and Quincke spinal needle types on the lateral distribution of small-dose 0.5% hyperbaric bupivacaine injected slowly into adult patients.
BACKGROUND: Cardiovascular function was assessed in 20 ASA I-II patients, scheduled for elective orthopaedic surgery with tourniquet in order to compare the haemodynamic changes induced by unilateral spinal anaesthesia and combined sciatico-femoral nerve block. METHODS: After baseline measurement of cardiovascular parameters, patients were randomized to receive unilateral spinal anaesthesia or combined sciatico-femoral nerve block. Spinal anaesthesia was obtained by 8 mg of hyperbaric bupivacaine 0.5% slowly injected (speed=0.02 ml s[-1]) through a 25-G Whitacre spinal needle with the bevel orientated towards the dependent side and patients lying on their operated side for 15 min (group S, n=10). Combined sciatico-femoral nerve block was obtained by 7 mg kg(-1) of mepivacaine 2% (group NB, n=10). Haemodynamic variables were recorded 5, 10, 15, and 30 min after anaesthetic injection before surgery was started. RESULTS: Anthropometric data, duration of surgery and acceptability of anaesthetic techniques were similar in the 2 groups. In 8 patients of group S, spinal block was restricted to the operated side (pinprick test and Bromage scale), while the other 2 patients developed bilateral spinal block after being turned supine. NB patients showed no haemodynamic changes during the study, whereas patients in group S showed a small but significant decrease of mean arterial blood pressure (P<0.002 vs baseline and P<0.04 vs NB), cardiac index (P<0.01 vs baseline and P<0.01 vs NB), and stroke volume index (P<0.01 vs baseline and P<0.01 vs NB). CONCLUSION: Both sciatico-femoral and unilateral spinal blockade provide adequate anaesthesia for unilateral leg surgery with tourniquet. The former technique affects cardiovascular performance less than the latter one.
Two new imidazo[2,1-b]thiazoles related to sulmazole were synthesized and subjected to an in vivo cardiotonic assay with 14 analog compounds which gave the best results in previously reported in vitro tests. The data obtained show that three substituents (3-pyridyl, 4-pyridyl and 2,5-dimethoxyphenyl group) are useful pharmacophoric groups in modulating the in vivo cardiotonic activity of the fused imidazoles considered.
The synthesis of 5-chloro-3-pyridylmethylene-2-indolinone is reported. This compound was subjected to an in vivo cardiotonic assay with 10 analogs whose synthesis and in vitro cardiotonic activity were previously reported. All the compounds tested (except the 5-hydroxyindole derivative) showed significant positive inotropic activity. The 3-pyridyl derivative without substituents at the indole system was the most active of the whole series.
In connection with a previous research dealing with the antitumor activity of imidazo[2,1-b]-thiazole guanylhydrazones, this paper reports the synthesis of new derivatives which were tested for antitumor and positive inotropic activity. In most cases the cytotoxic data from the in vitro experiments (HeLa) were in agreement with the antitumor data in vivo (Ehrlich). The active compounds bear a phenyl ring at the 6 position. On the other hand, the most active cardiotonic agents were devoid of the phenyl ring.
Two groups of 24 three-day-old turkeys each were inoculated with Eimeria meleagrimitis sporulated oocytes and fed a diet containing respectively 5 and 6 ppm of maduramicin ammonium. Clinical signs, mortality rates, weight gain, intestinal lesions and replication of the parasite were compared to the data obtained from a group of infected, untreated birds kept in the same experimental conditions over a period of 17 days. The treated birds showed better performances and less severe intestinal damages; the replication and the development of the parasite in the intestinal mucosa were impaired and delayed by the drug. All the data were dose dependent.
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The synthesis of 6-substituted 5-(thienylvinyl)imidazo[2,1-b]thiazoles and 6-thienylimidazo[2,1-b]thiazoles is reported. These compounds were tested as specific inhibitors of the NADH: ubiquinone (UBQ) reductase activity of NADH dehydrogenase in mitochondrial membranes. The 6-thienylimidazo[2,1-b]thiazoles were more potent in mammalian than in nematode mitochondria and had an average titer of 0.11 mM for 2-methyl-6-(2-thienyl)imidazo[2,1-b]thiazole (10). This compound is noncompetitive with the ubiquinone substrate and interacts with a site which is mutually exclusive with that of rotenone but nonexclusive with that of piericidin and several other inhibitors of NADH dehydrogenase. In the series of 5-(thienylvinyl)imidazothiazoles, the hydrobromide of (E)-6-chloro-5-(2-thienylvinyl)imidazo[2,1-b]thiazole (E-5.HBr) was found to be more potent as an inhibitor of the NADH:UBQ activity (IC50 = 15-17 microM) than the 6-thienylimidazoles such as 10. The inhibitory action of E-5.HBr and its analogs is different from that of compound 10 as indicated by the mutual exclusivity with other inhibitors and the relative inhibition of the activity with various electron acceptors.
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A new class of pyrrolo[1,4]benzodiazepine (PBD) analogues featuring a pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone ring system has been designed and synthesized. These compounds, 2a-o, are characterized by the substitution of the aromatic A ring, characteristic of the PBDs, with a disubstituted pyrazole ring bearing alkyl and benzyl substituents at N6 or N7 and alkyl or carbomethoxy substituents at C8. Biological evaluation revealed an appreciable in vitro cytotoxic activity for compounds 2a,b,f-i.
In connection with a previous study, new phenylindoles bearing a 2- or 3-thienyl group were synthesized and tested as specific inhibitors of mitochondrial NADH dehydrogenase. The position of the phenyl ring and the geometrical configuration play an important role in the activity and specificity of these derivatives. In order to study the mechanism of action of these thienylvinylindoles, their activity was compared with that of known inhibitors in a new test employing exogenous quinones.
A severe exudative-crustous and proliferous dermatitis in a 2 year old sheep caused by Dermatophilus congolensis (observed for the first time in Italy), is reported. The disease was reproduced experimentally in sheep, goats, rabbits and guinea pigs, whose skin was treated in different ways before infection. E.L.I.S.A. and Immunoblotting tests carried out in experimentally infected sheep, showed the antigenic complexity of the pathogen and the existence of cross-immunity to the protein components. Intradermoreaction tests were carried out in all animals. The development of a positive reaction only in rabbits and guinea pigs, confirmed that these animals have a cellular immunity against Dermatophilus congolensis.
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A new series of 1,4-dihydropyridine bearing substituted pyrazole and imidazole at C-4 position was synthesized and characterized as inotropic, chronotropic and calcium antagonist agents, in order to evaluate the effect on pharmacological activity of replacement of the 4-aryl group of nifedipine-like drugs by pyrazole and imidazole moieties. All compounds were tested on myocardial muscle and vascular smooth muscle of guinea-pigs. The new compounds showed both significant selective negative inotropic activity and fairly good negative chronotropic effects. All compounds elicited weak calcium antagonist activity, except compound 9 which is a selective bradycardic agent.