High isoproterenol doses are required to activate beta3-adrenoceptor-mediated functions in dogs

The "in vivo" conditions for beta3-adrenoceptors (beta-AR) activation by isoproterenol were investigated in dog. Experiments were carried out in anesthetized dogs using isoproterenol as a nonselective beta-AR agonist. Intravenous infusion of isoproterenol (0.4 nmol/kg/min) induced arterial hypotension and tachycardia with a slight decrease in cutaneous blood flow. At this dose, isoproterenol increased glucose, glycerol, and nonesterified fatty acid plasma levels. The changes in cardiovascular and endocrine-metabolic parameters, induced by the low dose of isoproterenol, were suppressed by pretreatment with nadolol (1 mg/kg, i.v.). After nadolol administration, however, a 10-fold higher dose (4 nmol/kg/min) of isoproterenol was able to induce a decrease in arterial blood pressure with a slight tachycardia and an increase in cutaneous blood flow. This high dose of isoproterenol increased nonesterified fatty acid and glycerol plasma levels but failed to change glucose plasma levels. All these effects were abolished by a pretreatment with nadolol (1 mg/kg, i.v.) plus SR59230A [a selective beta3-adrenoceptor antagonist; (3-(2-ethylphenoxy)-1(1S)-1,2,3,4-tetrahydronaphth-1-ylaminol-(2S)2-propanol oxalate); 1 mg/kg, i.v.]. Moreover, as observed with the high dose of isoproterenol under nadolol pretreatment, an infusion of SR58611A [a selective beta3-adrenoceptor agonist; ((N2S)-7-carbethoxymethoxy-1,2,3,4-tetrahydronaphth-2-yl-(2R)-2-hydroxy-2-chlorophenyl) ethanamine hydrochloride] induces a decrease in mean arterial blood pressure associated with an increase in heart rate, cutaneous blood flow, and nonesterified fatty acid and glycerol plasma levels. These results demonstrate that the in vivo activation of beta3-adrenoceptors requires higher doses of catecholamine than those necessary for beta1- and/or beta2-adrenoceptor stimulation. These results also argue for the lack of a beta3-AR involvement in the control of heart rate and glycogenolysis in dogs.     

临床与实验室共同努力 提高抗感染水平

提高临床抗感染疗效的关键是正确诊断,包括感染的诊断、病原菌的诊断和耐药性的诊断.面对日益复杂的病原菌和耐药性,临床与实验室应加强合作与交流,共同努力提高病原菌的诊断水平,正确报告和解读微生物检验报告,阐明细菌耐药机制,积极探索多重耐药菌的治疗方法;同时充分利用炎性指标的指导价值,努力提高抗感染水平.     

Heparin therapy in postoperative consumption coagulopathy in childhood]

On the basis of clinical symptoms and the results of coagulation tests, some changes in the blood coagulation similar to a consumption coagulopathy were found in eight children in the postoperative phase. In addition to the postoperative routine basic therapy a "low-dosage heparin therapy" was started. 3-5 IU of heparin/kg body weight/hour were administered in the form of a continuous intravenous infusion. The results are discussed.     

Heparin therapy for recent transient focal cerebral ischemia

The Mayo Clinic medical records and records linkage system were used to identify stroke-free residents of Rochester, Minnesota, who were examined within 30 days after the first transient cerebral ischemic attack (TIA) during the period 1955 through 1979. The patients were divided into two groups: those given heparin within 30 days after the first attack and those not given heparin. Death, stroke, and either stroke or TIA were separate endpoints in Kaplan-Meier analyses of data from the day of initial examination through the 30th day thereafter. The probabilities of survival, survival free from stroke, and survival free from TIA for the heparin-treated group were not significantly different from those probabilities for the comparison group. The rate of hemorrhagic complications was 3.2 per 100 person-days of heparin therapy. Retroperitoneal hemorrhage, the most serious complication, was the cause of one death and one case of femoral neuropathy.     

Care of the bereaved when postmortems are required

There are two kinds of postmortem--those undertaken by coroners and those undertaken in hospitals. The rules for consent depend on the kind of postmortem, and families must be offered much fuller information than before the Alder Hey Inquiry. As a result, nurses need to be clear about what is involved in a postmortem so that they can support families in asking the right questions and understanding the consent issues involved.     

Heparin algorithm for anticoagulation during continuous renal replacement therapy

In patients with acute kidney injury and concomitant severe hyponatraemia or hypernatraemia, rapid correction of the serum Na⁺ concentration needs to be avoided. The present paper outlines the principles of how to adjust the Na⁺ concentration in the replacement fluid during continuous renal replacement therapy to prevent rapid changes of the serum Na⁺ concentration.     

Macrophages are required for neonatal heart regeneration

Myocardial infarction (MI) leads to cardiomyocyte death, which triggers an immune response that clears debris and restores tissue integrity. In the adult heart, the immune system facilitates scar formation, which repairs the damaged myocardium but compromises cardiac function. In neonatal mice, the heart can regenerate fully without scarring following MI; however, this regenerative capacity is lost by P7. The signals that govern neonatal heart regeneration are unknown. By comparing the immune response to MI in mice at P1 and P14, we identified differences in the magnitude and kinetics of monocyte and macrophage responses to injury. Using a cell-depletion model, we determined that heart regeneration and neoangiogenesis following MI depends on neonatal macrophages. Neonates depleted of macrophages were unable to regenerate myocardia and formed fibrotic scars, resulting in reduced cardiac function and angiogenesis. Immunophenotyping and gene expression profiling of cardiac macrophages from regenerating and nonregenerating hearts indicated that regenerative macrophages have a unique polarization phenotype and secrete numerous soluble factors that may facilitate the formation of new myocardium. Our findings suggest that macrophages provide necessary signals to drive angiogenesis and regeneration of the neonatal mouse heart. Modulating inflammation may provide a key therapeutic strategy to support heart regeneration.     

Heparin and heparan sulphate are inhibitors of human leucocyte elastase.

1. Heparin and heparan sulphate strongly inhibited human leucocyte elastase activity in an automated assay using the soluble substrate, n-succinyl-(L-alanine)3-p-nitroanilide (50% inhibition of 250 microliters of 10 micrograms of human leucocyte elastase/ml was obtained with 80 microliters of 2.8 micrograms of heparin/ml and 8 micrograms of heparan sulphate/ml). Less significant inhibition at the same concentrations was seen with the other glycosaminoglycans tested: hyaluronic acid and chondroitin sulphates A-C. 2. Heparin and heparan sulphate also strongly inhibited human leucocyte elastase activity towards insoluble human lung elastin, as determined by an e.l.i.s.a. for soluble elastin-derived peptides released by elastolytic activity on the elastin. This inhibition was shown not to be due to a direct interference of the glycosaminoglycans in the e.l.i.s.a. nor to the inhibition causing a change in the size of the elastin-derived peptides. However, unlike the chromogenic assay with n-succinyl-(L-alanine)3-p-nitroanilide as substrate, where heparin was the more effective inhibitor, in this assay system heparan sulphate was the more effective inhibitor (50% inhibition of 100 microliters of 50 ng of human leucocyte elastase/ml was obtained with 100 microliters of 4.5 micrograms of heparin/ml and 0.8 microgram of heparan sulphate/ml). These results suggest that heparin and heparan sulphate, as components of cellular and basement membranes, are likely to have a role in protecting structural proteins, such as elastin, from the proteolytic activity of human leucocyte elastase.(ABSTRACT TRUNCATED AT 250 WORDS)     

High doses of warfarin are more beneficial than its low doses in patients with deep vein thrombosis

Background

The efficacy and safety of enoxaparin in outpatient treatment of deep vein thrombosis have been well studied. The present study aimed to compare the efficacy of a 10-mg loading dose of warfarin with 5 mg of the drug and enoxaparin in achieving the international normalized ratio (INR) range.

Methods

This randomized clinical trial was performed in the emergency department (ED) of our study. International normalized ratio was checked daily for 7 days and on the 14th day. Based on the patient's INR on the third day, the doses were adjusted. Patients received enoxaparin (1.5 mg/kg per day) simultaneously until the therapeutic range of INR was achieved for 2 consecutive days.

Result

The side effects were compatible in both groups. There was a significant difference in the INR rates of the 2 groups recorded on the third, fourth, and seventh days.

Conclusion

The 10-mg loading dose of warfarin induces the therapeutic range of INR earlier than the 5-mg dose without causing any significant difference in the side effects. More cases in the 10-mg group had INR levels higher than 3; the very dose, therefore, is recommended as the loading dose in cases of outpatients with deep vein thrombosis referring to the ED. Tight control of INR, after the third day of treatment, is also recommended in these cases.     

Heparin is not required for detection of antibodies associated with heparin-induced thrombocytopenia/thrombosis.

Heparin-induced thrombocytopenia (HIT), with or without thrombosis, is a common and often serious complication of heparin therapy. Platelet-activating, heparin-induced antibodies characteristic of HIT are thought to be specific for complexes formed between platelet factor 4 (PF4) and heparin, and such complexes are routinely used for antibody detection. We studied the binding of HIT antibodies to PF4 complexed with heparin fractions of uniform molecular size or linear polyanions other than heparin and found that many compounds other than heparin form complexes with PF4 that are suitable for antibody detection, provided they carry strong negative charges spaced about 0.5 nm apart along the molecular backbone and are of sufficient length to span about 40% of the circumference of the PF4 tetramer. Polyvinyl phosphonate was among the compounds that were equivalent to heparin. Thus neither a polysaccharide chain nor sulfate side groups--the hallmarks of heparin structure--are required for HIT antibody detection. The findings support the view that antibodies associated with HIT are specific for conformational changes that take place in the positively charged PF4 molecule when it reacts with a suitable, linear polyanion.