Macrolactonizations in the total synthesis of natural products.
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Biological Products↗
Biomedical subjects
X Moreau
Publications and source records attributed to X Moreau.
Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study.
Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.
Adult↗
Evidence for the presence of serotonin in Mysidacea (Crustacea, Peracarida) as revealed by fluorescence immunohistochemistry.
In crustaceans, serotonin (5-HT) exerts a wide range of physiological actions on many tissues. However, 5-HT has not been detected to date in Mysidacea (Crustacea, Peracarida). We have investigated the presence of 5-HT in the brain and the eyestalks of two Mysida (Leptomysis lingvura, Hemimysis margalefi) and one Lophogastrida (Lophogaster typicus) species by using the immunohistofluorescence technique. 5-HT-like immunopositive areas exhibit a similar pattern in the three species. 5-HT-like immunostaining is present in the retinular photosensitive cells, except in the deep-living species L. typicus. 5-HT-like cell bodies and fibres are observed in the lamina ganglionaris and in the three medullae. In the sinus gland, only 5-HT-like endings are detected. In the eyestalks, 5-HT-like fibres detected in the optic tract link with the protocerebrum, in which 5-HT-like somata and their extensions are found. Some neurones are detected in the anterior median cell cluster, in the protocerebral bridge and in the central body. In the deutocerebrum, the paracentral lobes are connected by immunoreactive fibres that run along the deutocerebral commissure. The glomeruli of the olfactory lobes exhibit strong diffuse immunostaining. Beside and in the median part of the deutocerebrum, at least two large serotoninergic neurones project their axons into the olfactory lobe cell cluster. Immunoreactive fibres are also found in the antennular neuropiles. Our results demonstrate the presence of 5-HT-like cell bodies and fibres in Mysidacea. The distribution patterns of the 5-HT immunoreactivity found herein are compared with those of other peracarids and decapods.
Animals↗
Chronic effects of triiodothyronine in combination with imipramine on 5-HT transporter, 5-HT(1A) and 5-HT(2A) receptors in adult rat brain.
Triiodothyronine (T3) has been shown to accelerate and potentiate the clinical response to tricyclic antidepressant (TCA) treatment in depressive disorders. The neurobiological mechanisms underlying these therapeutic effects of T3 are still unknown. Since brain serotonin (5-HT) changes have been implicated in the mode of action of TCA drugs, the effects of a chronic (7 or 21 days) administration of imipramine (10 mg/kg/day) and of a low dose of T3 (4 microg/kg/day), given alone or in combination, were investigated on the density of midbrain 5-HT transporters and of hippocampal 5-HT(1A) and cortical 5-HT(2A) receptors in adult Wistar rats. Neither single nor combined administration of imipramine and T3 for 7 days modified the density of 5-HT transporters and of 5-HT(1A) receptors. On day 21, the combination did not change imipramine- or T3-induced decrease in 5-HT transporter density whereas it prevented imipramine-induced increase in 5-HT(1A) receptor density. Whatever the treatment duration, imipramine-T3 combination potentiated imipramine-induced decrease in 5-HT(2A) receptor density. On both day 7 and day 21, T3 given alone had no effects on the density of 5-HT(1A) and 5-HT(2A) receptors. These data indicate that T3 is able to modulate the long-term adaptive changes which occur at the postsynaptic level of 5-HT neurotransmission after antidepressant treatment.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Red blood cell triiodothyronine uptake in unipolar major depression: effect of a chronic antidepressant treatment.
The evolution of kinetic parameters (Vmax, maximal velocity, and Km, Michaelis constant) of red blood cell (RBC) triiodothyronine (L-T3) initial uptake was followed in 19 inpatients suffering from unipolar depression after 1 week (D7) and 4 weeks (D28) of a chronic administration of fluvoxamine, in relation with the clinical efficacy of the drug. In a drug-free state (DO), Vmax (in pmol/min/10(8) cells) and Km (in nM) were significantly increased in depressed patients (Vmax +/- S.D.= 1.02 +/- 0.29, p< 0.01 and Km +/- S.D.= 68.8 +/-15.4, p< 0.05; n=19) compared to healthy volunteers matched for age and sex (Vmax +/- S.D.= 0.82 +/- 0.15 and Km S.D.= 58.8 +/- 9.0; n= 19). When patients were dichotomized on the basis of their treatment response, responders had kinetic parameters significantly increased (Vmax +/-S.D.= 1.03 +/- 0.26, p< 0.01 and Km +/- S.D.= 71.7 +/- 18.7, p< 0.05, n= 10) compared to controls, whereas non-responders had not (Vmax +/- S.D.= 1.00 +/- 0.33, NS and Km +/- S.D.= 65.7 +/- 10.9, NS, n= 9). At D7, Vmax differed from the one of controls only in the responders (Vmax +/- S.D.= 1.03 +/-0.26, p< 0.01). In addition, the percentage of variation of the individual Vmax values during the first week of treatment was significantly lower in responders than in non-responders (deltaVmax(D7-D0) +/- S.D. in % = 10.7 +/- 6.0 and 22.0 +/- 11. 1, p< 0.05, respectively). At D28, kinetics of L-T3 uptake normalized only in the responders (Vmax +/- S.D.= 0.91 +/- 0.13, NS; Km+/-S.D.= 65.7 +/- 7.4, NS). The results indicate that both RBC L-T3 uptake at the pretreatment level and its change during the first week of fluvoxamine treatment were related to the further clinical response to the antidepressant. RBC L-T3 uptake seems to be a biological correlate of the depressive symptomatology since the disturbances disappear only with the clinical remission.
Adult↗
Kinetics of red blood cell T3 uptake in hypothyroidism with or without hormonal replacement, in the rat.
L-triiodothyronine (L-T3) is taken up and accumulated into red blood cells (RBC) by means of a specific carrier-mediated system. The aim of this study was to evaluate the reactivity of this system in relation to induced alterations in thyroid hormone (TH) supply. We investigated the kinetic parameters (Vmax, maximal velocity and Km, Michaelis constant) of washed-RBC L-T3 uptake 1) in thyroidectomized (TXT) rats, 2) in TXT rats administered with low doses of L-T4 (15 microg/kg/day x 14) to restore normal serum TH levels (REPL), 3) in TXT rats administered with high doses of L-T4 (200 microg/kg/day x 14) to achieve a large increase in serum TH levels (HIGH). Serum free T3 and T4 levels were significantly decreased in TXT rats (2.4 and 8.8 fold, respectively), not different in REPL rats and significantly increased in HIGH rats (2.4 and 3 fold, respectively) compared to sham-operated rats (SHAM). Both kinetics of RBC L-T3 uptake were significantly increased in TXT rats (Vmax+/-SE in pmol/min/10(8) cells=235.1+/-11.1, p<0.05 and Km+/-SE in nM=190.1+/-9.0, p<0.05), not different in REPL rats (Vmax=1 84.8+/-7.6 and Km=151.9+/-7.1) and significantly decreased in HIGH rats (Vmax=168.0+/-4.1, p<0.01 and Km=131.9+/-4.6, p<0.01) compared to SHAM rats (Vmax=197.7+/-5.8 and Km=160.9+/-6.1). These results show that kinetics of RBC L-T3 uptake are modified in response to defect or excess in circulating TH levels. Since RBC play likely a role of a buffer system, the changes in carrier-mediated influx of L-T3 could be seen as a compensatory mechanism that counteract the disturbances in the TH availability for the target tissues.
Animals↗
Effects of experimental hypothyroidism on 5-HT1A, 5-HT2A receptors, 5-HT uptake sites and tryptophan hydroxylase activity in mature rat brain1.
The study was aimed at investigating the repercussions of deficiency in thyroid function with and without thyroid hormone (TH) replacement on the neurochemical entities which underly serotonin (5-HT) neutrotransmission, namely 5-HT1A, 5-HT2A receptors, 5-HT transporter and tryptophan hydroxylase (TPH) in the mature brain. Surgically thyroidectomized male Wistar rats received: (1) an iodine-free diet to produce severe hypothyroidism; (2) hormonal replacement with 15 microgram/kg/day of thyroxine (T4) for 21 days to normalize serum TH levels, or (3) hormonal replacement with 200 microgram/kg/day of T4 for 14 days to produce an excess of circulating THs. Sham-operated rats were used as controls. Neither hypothyroidism nor an excess in serum TH levels affected 3H-8-OH-DPAT binding to 5-HT1A receptors, 3H-citalopram binding to 5-HT transporter and TPH activity in various brain structures indicating that, in the mature brain, the presynaptic entities of 5-HT neurotransmission are resistant to large variations in TH levels. By contrast, hypothyroid rats had a significant decrease in Bmax of 3H-ketanserin binding to cortical 5-HT2A receptors compared to controls. Cortical 3H-ketanserin binding in thyroidectomized rats was normalized after replacement with low-dose T4. Excess serum TH levels in thyroidectomized rats did not produce any changes in cortical 5-HT2A receptors when compared to thyroidectomized rats with normalized TH levels. The present data suggest that the decrease in cortical 5-HT2A receptors is the main neurochemical event underlying the impairing effect of hypothyroidism on 5-HT neurotransmission.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Increase in red blood cell triiodothyronine uptake in untreated unipolar major depressed patients compared to healthy volunteers.
1. Kinetic parameters of red blood cell (RBC) L-triiodothyronine (T3) initial uptake (Vmax, maximal velocity and Km, Michaelis constant) were determined in 34 untreated inpatients suffering from unipolar depression and in 40 healthy volunteers. 2. Both Vmax and Km were significantly increased in depressed patients as compared to controls. The alterations in kinetic parameters were not associated with the severity of depression. 3. Out of the 19 depressed patients who were submitted to TRH test, 7 of them (36%) showed a blunted TRH-induced TSH response associated with a Vmax situated outside the control mean value +/- 1 S.D. 4. The authors found a significant positive correlation between Vmax of RBC L-T3 and L-tryptophan (TRP) uptakes which is in agreement with the assumption that L-T3 and L-TRP share a common carrier system at the erythrocyte level. 5. The results indicate that the uptake of L-T3 by RBC is increased in major depression. These transport perturbations might reflect alterations in the plasmatic metabolism of L-T3. Evaluation of RBC L-T3 uptake could be useful in a best biological characterization of the depressed patients with regard to their thyroid function.
Adult↗
[Comparison of vascular effects of magnesium sulfate and nicardipine during extracorporeal circulation].
OBJECTIVE: To evaluate the hypothesis that magnesium sulphate (SO4Mg), usually administered for protecting the myocardium and decreasing the rate of arrhythmias in cardiac surgery, was able to control the hypertensive peaks occurring during cardiopulmonary bypass (CPB), as efficiently as nicardipine (N). STUDY DESIGN: Randomized controlled trial. PATIENTS: Forty patients were allocated into two groups when hypertensive peaks occurred during CPB. The patients of the N group were then given nicardipine 0.016 mg.kg-1 and those of the SO4Mg group received magnesium sulphate 50 mg.kg-1. METHODS: Anaesthesia technique was identical and during normothermic CPB the flow remained constant at 2.4 L.min-1, during the 10 min following N or SO4Mg administration. The usual haemodynamic variables were monitored. RESULTS: Both N and SO4Mg decreased significantly the MAP and the SVR over the 9 min following their administration. The decrease was more marked after SO4Mg. As the flow of the pump was unchanged after their injection the decrease can be attributed to the relaxing effect of these agents on the smooth vascular muscles. CONCLUSIONS: SO4Mg permits to treat hypertensive peaks occurring during CPB as efficiently as N. Three grammes of SO4Mg have an hypotensive effect equivalent to that of 1 mg of nicardipine. However repetitive injections of SO4Mg cannot be recommended because of the risk for hypermagnesemia.
Aged↗
[Comparison of effects of aprotinin and tranexamic acid on blood loss in heart surgery].
OBJECTIVES: To compare the efficacy of aprotinin (APR) and tranexamic acid (TRA) in reducing blood loss and transfusion requirements after cardiac surgery under extracorporeal circulation (ECC). STUDY DESIGN: Randomized controlled trial. PATIENTS: One hundred and four adults undergoing either coronary artery bypass grafting (CABG) (n = 55), or aortic valve replacement (AVR) (n = 49), allocated into three groups. METHODS: a) APR group (23 CABG and 20 AVR) received aprotinin, 2 x 10(6) KIU (280 mg) after induction, followed by an infusion of 0.5 x 106 KIU.h-1 (70 mg.h-1) until chest closure, with a supplement to the oxygenator prime of 2 x 10(6) KIU; b) TRA group (22 CABG and 19 AVR) received tranexamic acid, 15 mg.kg-1 between the injection of heparin (400 IU.kg-1) and the beginning of ECC, 15 mg.kg-1 after protamin injection (1.3 mg/100 IU of heparin); c) CTR group (10 CABG and 10 AVR), the control group, was not treated with an antifibrinolytic agent. The amount of blood collected from the chest tube drainage was measured at admission to ICU, as well as 4, 8 and 18 h after the insertion of drains and at the time of their removal. Packed red cells where given when the haematocrit was under 20% during ECC, 25% at the end of surgery and 30% after extubation. RESULTS: The blood loss was lower in APR group (834 +/- 448 mL) than in TRA group (1015 +/- 409 mL) (P = 0.009), and in CTR group (1416 +/- 559 ML) (P = 0.004). The rates of transfused patients in groups APR, ATR and CTR were 35, 37 and 60% respectively and the numbers of units administered per patient were 0.8, 0.8 and 1.7 respectively. In AVR cases, APR and TRA had a similar efficacy. In CABG cases, only aprotinin decreased postoperative bleeding. However there was no difference between APR and TRA concerning the transfusion requirements. In CABG cases the ECC was of shorter duration and blood loss was 1127 +/- 540 mL vs 894 +/- 422 mL in AVR cases (P = 0.03). CONCLUSIONS: Both APR and TRA decrease blood loss. APR is more efficient after CABG than TRA as far as blood loss is concerned, whereas the transfusion requirements are similar. As APR is about 100 times more expensive and carries a risk for allergic reactions, its use in a high dose regimen is only recommended for reoperations, in patients treated with salicylates and in case of sepsis.
Adult↗
[Hemodynamic effects of intravenous diltiazem after immediate coronary revascularization].
Perioperative spasm of the internal mammary artery (IMA) may occur after coronary artery bypass surgery. Diltiazem is often used to prevent it. We studied the haemodynamic tolerance of this drug just after coronary artery bypass surgery, using an intravenous injection of 0.3 mg.kg-1 in 2 minutes. Fifteen patients were studied and the injection was performed less than one hour after the arrival of the patient in the intensive care unit. A reduction in systemic arterial blood pressure and a negative chronotropic effect was observed. There was no significant modification of cardiac output. Diltiazem used in that context has no myocardial depressant effect.
Anesthetics↗
[Long-term retrograde cerebral perfusion in surgery of the aortic arch. Apropos of 2 cases].
The authors present two cases of aortic arch replacement for aortic dissection: one in a male patient 58 years old and the other in a female patient 78 years old. Cerebral protection during repair of the aortic arch was performed with retrograde cerebral perfusion (RCP). Durations of RCP were 75 and 120 minutes respectively. Good neurological recovery in both patients appeared to confirm the efficacy of RCP with respect to cerebral protection during surgery of the aortic arch.
Aged↗
[Retrograde cerebral perfusion for replacement of the aortic arch. Apropos of a case].
The authors report a case of cerebral protection with retrograde cerebral perfusion during aortic arch surgery. The duration of retrograde cerebral perfusion and the favorable neurological outcome seem to confirm the promising results of this technique developed in Japan.
Aortic Dissection↗
[Cardiac surgery in aged patients; immediate and medium-term results in 100 patients over 75 years of age].
With improved operative technique and postoperative care, progressively older patients are being referred for cardiac surgery. One hundred out of 633 patients operated between September 1990 and December 1992, were over 75 years of age (Group I). These patients were compared with the last 100 patients under 75 years of age (Group II). Both groups were operated by the same surgical team with the same anaesthetic, cardiopulmonary bypass and myocardial protection techniques. The average age of the groups was 79.5 +/- 3.1 and 62.1 +/- 9.2 years, respectively. The procedures performed were: myocardial revascularisation (Group I, 28 cases; Group II, 59 cases), aortic valve surgery alone or associated with coronary bypass (56 and 22 cases respectively), and mitral valve surgery alone or associated with another procedure (11 and 12 cases). There were no significant differences between the two groups with respect to true low output state, the duration of mechanical ventilation and of intensive care and hospital stay. On the other hand, there were significant differences in: the number of blood transfusions (44 cases versus 20, p < 0.001), the occurrence of atrial fibrillation (52 cases versus 29, p < 0.001) and neuropsychiatric disturbances (27 cases versus 5, p < 0.0001). There were no cases of mediastinitis in either group. The hospital mortality was 6% in Group I and 5% in Group II (NS). The medium-term mortality after an interval of 5 to 32 months in the over 75 age group was 7 cases, including 4 cases of cerebrovascular accident. An enquiry was performed in the 87 survivors of Group I.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Decrease of isoprene concentrations in blood during general anesthesia.
Isoprene is present in human breath and in human blood. The fact that isoprene concentrations in breath are linked to states of sleep and wakefulness led us to study its concentration in blood of 12 patients before, during, and after general anesthesia. Isoprene concentrations in blood of patients before anesthesia were 3.3 +/- 1.6 micrograms/liter. During anesthesia, isoprene concentrations decreased to 0.9 +/- 0.5 micrograms/liter. One hour after the end of anesthesia isoprene increased to levels similar to or higher than the preanesthetic ones.
Adult↗
Heparin-associated thrombocytopenia syndrome: an underestimated etiology of adrenal hemorrhage.
A 74-year-old man developed bilateral arterial thrombosis of the lower limbs related to heparin-associated thrombocytopenia syndrome (HATS). On day 4 after thrombectomy of both limbs, abdominal pain, fever, hypotension, abdominal tenderness appeared. Acute acalculous cholecystitis was suspected and cholecystectomy was carried out although the gallbladder was not imflamed. Later on, hyponatremia in addition to the aforesaid signs suggested the diagnosis of adrenal insufficiency. Diagnosis was confirmed by low cortisol and aldosterone plasma concentration and by CT scan, which showen two enlarged adrenal glands. HATS might explain two unexpected facts: occurrence of adrenal hemorrhage during heparin therapy with coagulation tests within the therapeutic range and paradoxical thrombosis in the central vein of adrenal gland. HATS must be regarded as one cause of adrenal hemorrhage necrosis.
Adrenal Gland Diseases↗
[Anaphylactic shock during the use of high doses of aprotinin in cardiac surgery].
A 77-year-old man was admitted for mitral valve replacement, 46 days after a failed conservative mitral surgery where he received high-dose aprotinin. Twenty minutes after induction of anaesthesia, 250 UPh E of aprotinin were infused intravenously; before the end of this infusion, bronchospasm, systemic hypotension and generalized rash were noted. Immediate treatment included intravenous adrenaline and methylprednisolone; cardiovascular stability was restored after 10 minutes. Immediate histamine liberation was confirmed by the analysis of the time course of the clinical events, a previous contact and positive skin tests. Aprotinin has the antigenic molecular structure of natural proteins. Since 1987, it is used in cardiac surgery to reduce postoperative blood loss: to prevent serious allergic reactions to aprotinin, it is necessary, in patients known to have had previous aprotinin therapy, to perform skin testing with diluted aprotinin before infusion.
Aged↗
[Iloprost (Ilomedine) and extracorporeal circulation with conventional heparinization in a patient with heparin-induced thrombocytopenia].
A 73-year-old female patient was admitted for myocardial infarction. Conventional treatment with heparin was started, intraaortic balloon assistance was required for several days, together with heparin. The platelet counts decreased progressively, from 288 G.l-1 on admission to 41 G.l-1 on the 16th day, despite the use of low molecular weight heparin. The in vitro heparin platelet aggregation test remained positive. This aggregation ended on adding iloprost, an analogue of prostacyclin, to the platelet culture bath. A coronary aortic bypass graft was required. An infusion of iloprost was started just after induction of anaesthesia. The initial dose of 0.5 ng.kg-1 x min-1 was gradually increased to 20 ng.kg-1 x min-1. Heparin (400 IU.kg-1) was thereafter added. To maintain a mean blood pressure of a least 50 mmHg, an infusion of up to 10 micrograms.kg-1 x min-1 of phenylephrine was given. As it was insufficient, an infusion of up to 1 microgram.kg-1 x min-1 noradrenaline was required. The iloprost infusion was gradually stopped 15 min before the end of CPB, together with that of noradrenaline. Platelet aggregation tests were positive after protamine had been given, whereas they had been negative during the infusion of iloprost. There was no abnormal postoperative bleeding. An infusion of 2 ng.kg-1 x min-1 was started at the sixth postoperative hour for 48 h, until the coumarin-like agent had started taking its effects. It is concluded that iloprost might be useful for carrying out cardiac surgery in patients with heparin-induced thrombocytopaenia.
Aged↗