[How I treat diabetic dyslipemia in the framework of preventing cardiovascular pathology].
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Cardiovascular Diseases↗
Biomedical subjects
S Bernard
Publications and source records attributed to S Bernard.
Synthesis and in vivo studies of a specific monoamine oxidase B inhibitor: 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)- 1,3,4-oxadiazol-[11C]-2(3H)-one.
We report the radiochemical synthesis of a specific MAO B inhibitor, namely 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-[11C]-2(3 H)-one (2b) (in vitro IC50=4nM and selectivity over 71000 for MAO B), by cyclization of its hydrazide precursor 1 with [11C]phosgene. The reaction occurred within 2 min. The product obtained after HPLC purification, 2b, had a high specific activity (11.1-22.2 GBq/micromol), allowing its use in experiments as a radiotracer in vivo. Biodistribution of 2b in the CNS and in the peripheral organs of the rat, and positron emission tomography (PET) studies in the living baboon brain, pretreated or not with L-deprenyl (1mg/kg, 1h), an irreversible MAO B-specific inhibitor, were undertaken. The results showed a good uptake of 2b in all organs of the rat, with a rapid clearance from the blood (10 min). Metabolite analyses in plasma and in the diencephalon of the rat showed that 2b was the only radioactive compound in brain structure whereas in plasma three other radioactive products appeared. PET experiments show that in the L-deprenyl-pretreated baboon brain, specific binding of 2b represents around 70% of total radioactivity, whereas in the blood and plasma the radioactivity cleared rapidly (15 min).
Animals↗
Treatment of angioimmunoblastic lymphadenopathy with dysproteinemia using 2-chlorodeoxyadenosine.
Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is an atypical lympho-proliferative disorder with borderline features that often constitute a diagnostic challenge for the hematopathologist and a therapeutic dilemma for the treating clinician. Morphologically, the involved lymph nodes in this disorder are characterized by abnormal infilitration by immunoblasts and plasma cells, often in clusters or sheets. Regressed follicles may be seen; these are referred to as "burned out." Neovascularization is prominent, and a background of inflammatory cells is usually present. AILD was originally thought to represent an exaggerated autoimmune response. Because of the short median survival of the patients and the demonstration of T-cell clonality, AILD now is considered an aggressive lymphoma and is recognized as a subset of peripheral T-cell lymphoma by the REAL classification. In this article we present a patient with AILD who achieved durable partial remission after treatment with one cycle of 2-chlorodeoxyadenosine.
Adult↗
Immunohistochemical study on the reactivity of workshop monoclonal antibodies with sheep lymph nodes.
Of the 302 monoclonal antibodies submitted to the Third Workshop on Ruminant Leukocyte Antigens, 167 have been tested for their reactivity on sheep lymph node sections, according to the APAAP immunohistochemical technique. Of the 57 monoclonal antibodies able to react on ovine tissue sections, only 37 induced a clear and well-contrasted staining. The more striking results are presented in this paper.
Animals↗
Flow cytometric analysis of the reactivity of workshop monoclonal antibodies on sheep lymph node cells, after infection with Salmonella abortusovis.
Of the 302 monoclonal antibodies included in the Third Workshop on Ruminant Leukocyte Antigens, 167 have been tested for their reactivity on uninfected and Salmonella-infected sheep lymph node leukocytes using FACS analysis. Only 47 of them showed specificities which could be related to those of some control monoclonal antibodies, such as the anti-CD5, anti-Ig light chain and anti-MHC Class II monoclonal antibodies.
Animals↗
Changing the relationship among nurses' knowledge, self-reported behavior, and documented behavior in pain management: does education make a difference?
An educational program designed to change knowledge in order to change pain management practices and patient outcomes was offered to nurses who provide day-to-day care to patients with cancer in communities in a predominantly rural state. A quasi-experimental time-series design was used to measure the effectiveness of the program in changing nurse knowledge, attitude and behavior, and to evaluate the relationships between the outcomes. Data were collected from nurses (N = 29) and patient charts before (N = 209) and after (N = 163) the program. Nurses' knowledge increased, but the change was not statistically significant; the mean percent of correct answers on the three subtests were different and differences persisted throughout the study. Nurses believed that patients should be "pain free." Documentation of behaviors, for example, practice activities, occurred infrequently and showed little change until 6 months after the program. Increase in documentation of pain-intensity ratings, pain location, number of sites of pain, presence of confusion, anxious or depressed mood, sleep, nausea and vomiting, constipation, and general activity were noted. Documentation of the use of a propoxyphene-containing analgesic decreased; increase in the use of hydromorphone methadone and transdermal fentanyl was noted. Analysis of the relationships between correct responses to nurse knowledge questions and documentation of behavior provided interesting, statistically insignificant results that need to be reexamined in future research. Future programs should emphasize analgesic dosing and calculation of equianalgesic doses. Current practices in chart documentation may provide incomplete information regarding change in practice behaviors; more detailed documentation of pain management practices is needed. Nurses who participated in the program anecdotally reported feelings of increased credibility and effectiveness. Although change in behavior is slow to occur, education does make a difference.
Adult↗
Characterization of an Escherichia coli mutant, feeA, displaying resistance to the calmodulin inhibitor 48/80 and reduced expression of the rare tRNA3Leu.
We previously described a mutation feeB1 conferring a temperature-sensitive filamentation phenotype and resistance to the calmodulin inhibitor 48/80 in Escherichia coli, which constitutes a single base change in the acceptor stem of the rare tRNA3Leu recognizing CUA codons. We now describe a second mutant, feeA1, unlinked to feeB, but displaying a similar phenotype, 48/80 resistance and a reduced growth rate at the permissive temperature, 30 degrees C, and temperature-sensitive, forming short filaments at 42 degrees C. In the feeA mutant, tRNA3Leu expression (but not that of tRNA1Leu) was reduced approximately fivefold relative to the wild type. We previously showed that the synthesis of beta-galactosidase, which unusually requires the translation of 6-CUA codons, was substantially reduced, particularly at 42 degrees C, in feeB mutants. The feeA mutant also shows drastically reduced synthesis of beta-galactosidase at the non-permissive temperature and reduced levels even at the permissive temperature. We also show that increased copy numbers of the abundant tRNA1Leu, which can also read CUA codons at low efficiency, suppressed the effects of feeA1 under some conditions, providing further evidence that the mutant was deficient in CUA translation. This, and the previous study, demonstrates that mutations which either reduce the activity of tRNA3Leu or the cellular amount of tRNA3Leu confer resistance to the drug 48/80, with concomitant inhibition of cell division at 42 degrees C.
Codon↗
Induced hypothermia in intensive care medicine.
Induced hypothermia as adjunctive therapy has been the subject of considerable research interest and debate for over fifty years. Recently the first prospective randomized controlled trials were undertaken in humans with severe traumatic brain injury, with supportive results. Another prospective controlled study of induced hypothermia in severe septic adult respiratory distress syndrome also suggested improved outcome. Other studies in patients with anoxic brain injury have been suggested following promising findings in animal models. There have been anecdotal reports of the use of induced hypothermia in a wide range of other neurological injuries. There are significant physiological changes during induced hypothermia, particularly affecting the cardiovascular system. In addition, hypokalaemia, prolonged clotting times and neutropenia may occur. The evidence that induced hypothermia may be hazardous is mostly drawn from the literature on accidental hypothermia occurring in trauma, or patients with sepsis. It is likely that further trials will be conducted and if benefit is confirmed, induced hypothermia may become more widely used in selected patients in the intensive care unit.
Animals↗
Effects of low-protein diet supplemented with ketoacids on plasma lipids in adult chronic renal failure.
We designed a short-term randomized controlled study in 12 adult patients with chronic renal failure to assess the metabolic effects of a low-protein diet (LPD) supplemented or not with ketoacids (Cetolog, Clintec Corp., France). Dietary survey included a monthly 3-day food record and a 24-hour urinary urea measurement. After a baseline period (1.11 g protein, 31.7 kcal/kg BW/day), patients reduced their protein intake (PI) to 0.71 g/kg BW/day. Energy intake (EI) was kept constant (31.4 kcal/kg BW/day) during the 3-month period. Baseline plasma lipids did not show overt hyperlipemia. After reducing PI, a significant increase in apolipoprotein AI and the Apo-AI/Apo-B ratio was observed. Plasma Lp(a) levels were elevated at baseline and did not change during the 3-month LPD period. There was no difference between groups receiving ketoacids or not. Thus, in adult chronic renal failure, under a sufficient EI, reducing PI by 40% had a beneficial effect on plasma lipid profile. This improvement in lipid profile might reduce the high cardiovascular risk in these patients.
Adult↗
'Emergency room' thoracotomy: is it ever justified?
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Emergency Service, Hospital↗
[Recombinant human growth hormone (rhGH) administration in a patient with chronic renal insufficiency: renal and metabolic effects].
We report the renal and metabolic effects of a 40 day administration of recombinant human growth hormone in a 31 years old diabetic and GH-deficient patient who underwent a kidney and pancreas transplantation. The data show an increase in glomerular filtration rate, tubular reabsorption of phosphate, and plasma hemoglobin level. Anabolism is suggested from a decrease in serum urea nitrogen and an increase in muscle mass (increase in plasma creatinine). These positive effects might be partly explained by an overcome of endogenous growth hormone resistance when administering pharmacological doses of recombinant growth hormone.
Adult↗
Selective and potent monoamine oxidase type B inhibitors: 2-substituted 5-aryltetrazole derivatives.
Twenty new 2-(cyanoalkyl)tetrazoles (15 and 16) and twenty new 2-(hydroxyalkyl)tetrazoles (17 and 18) were synthesized and investigated in vitro for their abilities to inhibit selectively rat brain monoamine oxidase (MAO) B over MAO A. Most of them were MAO B inhibitors and those bearing a substituted 4-(arylmethoxy)phenyl group in the position 5 of the tetrazole ring had IC50 values between 8 microM for 18d and 2 nM for 16a (30 nM for lazabemide) with a selectivity toward MAO B of 37,000 for 16a. The reversibility of their inhibitory activity was demonstrated by in vitro dialysis tests. The 5-[4-(phenylmethoxy)phenyl]-2-(2-cyanoethyl)tetrazole (16a) its derivative 16h and the 5-[4-(phenylmethoxy)phenyl]-2-(2-hydroxyethyl)tetrazole (18a) and its derivative 18h were found to be potent, in vitro selective, and competitive MAO B inhibitors. Tetrazole 16a can be considered one of the most active and selective competitive MAO B inhibitors known up to now. This compound was selected for ex vivo experiments and was shown to be a strong and reversible MAO B inhibitor with a short duration of action after oral administration at 5 mg/kg. The structure-activity approach gives rise to the great importance of lipophilicity over electronic effects of the compounds in these series.
Animals↗
Structural and electronic properties of liquid boron from a molecular-dynamics simulation.
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Journal Article↗
Another man-made crisis in Rwanda: international community at fault.
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Food Supply↗
Functional domains in the spike protein of transmissible gastroenteritis virus.
The coronavirus spike protein S is assumed to mediate essential biological functions, including recognition of target cells. Earlier studies from our and other groups identified two regions of the TGEV S (220K) protein possibly implicated in such functions. The first of these corresponds to the 224 amino acid N-terminal region which is deleted in PRCV, the respiratory variant of TGEV. We have examined the pathogenicity for the newborn piglet of a series of neutralization escape mutants encoding an S protein mutated in this region. Several amino acid changes were correlated with a dramatic loss of enterovirulence, thus indicating that crucial determinants are associated with this domain of S. The second region of potential relevance is the major neutralization domain. Baculovirus-vectored expression of 150 to 220 amino acid-long stretches encompassing this region, which is encoded by both TGEV and PRCV, was performed. The resultant recombinant proteins were shown to react with the cognate antibodies and to bind APN specifically, thus localizing the receptor-binding site on the S primary structure. Altogether these data lend support to the view that a domain of S protein structurally distinct from the receptor binding site is required for the virus to express its enteric tropism.
Amino Acid Sequence↗
Combining percutaneous bypass with coronary retroperfusion limits myocardial necrosis.
After an acute coronary occlusion that results in hemodynamic instability, the institution of percutaneous bypass (PB) can effectively support the failing myocardium. However, PB cannot augment coronary blood flow, and substantial regional myocardial necrosis can still occur. This experimental study was undertaken to determine whether combining PB with coronary venous retroperfusion using pressure-controlled intermittent coronary sinus occlusion (PICSO) would limit myocardial necrosis after an acute coronary occlusion. In 30 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, 10 pigs were placed on PB, 10 pigs received PB+PICSO, and 10 pigs received no support (unmodified). Hearts treated with the combination of PB+PICSO had the highest wall motion scores (unmodified, 1.4 +/- 0.3; PB, 1.4 +/- 0.3; PB+PICSO, 2.8 +/- 0.3 [p < 0.05 versus unmodified and PB]) and the lowest area of necrosis in the area at risk (unmodified, 73% +/- 3%; PB, 43% +/- 2%; PB+PICSO, 14% +/- 2% [p < 0.05, PB and PB+PICSO versus unmodified; p < 0.05, PB+PICSO versus PB]). We conclude that combining PB with coronary venous retroperfusion significantly limits myocardial necrosis.
Animals↗
Limiting ischemic myocardial damage using glucose-insulin-potassium solutions.
BACKGROUND: This experimental study sought to determine whether the infusion of glucose-insulin-potassium (GIK) solutions to ischemic myocardium during revascularization would decrease myocardial damage. METHODS: In 40 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the periods of coronary occlusion and reperfusion, 10 pigs received GIK (glucose = 300 g/L, insulin = 50 U/L, K+ = 80 mEq/L) through the jugular vein at 1 mL.kg-1.h-1 (GIK-IV group); 10 pigs received GIK through the coronary sinus (GIK-CS group); 5 pigs received GIK through the jugular vein during reperfusion only (GIK-R group); 5 pigs received GIK through the jugular vein 2 hours prior to coronary occlusion and then during the periods of coronary occlusion and reperfusion (GIK-Pre group); and 10 pigs received no GIK (Unmodified group). Ischemic damage was assessed by wall motion scores using two-dimensional echocardiography, changes in myocardial tissue pH, and the area of necrosis in the area of risk. RESULTS: Hearts treated with GIK had significantly less tissue acidosis, higher wall motion scores, and the least tissue necrosis (14% +/- 2% GIK-Pre versus 12% +/- 2% GIK-CS versus 16% +/- 2% GIK-IV versus 25% +/- 2% GIK-R versus 73% +/- 4% Unmodified; all, p < 0.05 versus Unmodified). CONCLUSIONS: We conclude that a glucose-insulin-potassium solution reduces ischemic myocardial damage during coronary revascularization.
Animals↗
Role of leukocyte depletion during cardiopulmonary bypass and cardioplegic arrest.
BACKGROUND: Leukocyte depletion (LD) has been shown to be beneficial during the reperfusion of acutely ischemic myocardium; however, its role during cardiopulmonary bypass (CPB) in hearts protected with blood cardioplegia (BCP) is unknown. This experimental study sought to determine whether LD filters inserted in the CPB circuit before cardioplegic arrest and in the BCP circuit during arrest would decrease ischemic myocardial damage. METHODS: In 20 pigs, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of BCP arrest and 180 minutes of reperfusion on CPB. In 5 pigs, LD filters were inserted in both the CPB and BCP circuits (LD-CPB+BCP). Five pigs had LD during BCP (LD-BCP), 5 pigs had LD during CPB (LD-CPB), and 5 pigs had no LD. Ischemic damage was assessed by wall motion scores using two-dimensional echocardiography and the area of necrosis/area of risk. RESULTS: The LD-CPB and LD-CPB+BCP groups had the highest wall motion scores and the lowest area of necrosis/area of risk. The addition of LD to BCP alone did not significantly alter wall motion scores or the area of necrosis/area of risk. CONCLUSION: Leukocyte depletion filters significantly reduce ischemic damage during acute surgical revascularization and appear to be most effective when placed in the CPB circuit before cardioplegic arrest.
Animals↗