Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits the coagulant proteinase alpha-thrombin. We have recently demonstrated that proteolysis of HC by catalytic amounts of polymorphonuclear leukocyte proteinases (elastase or cathepsin G) generates leukocyte chemotaxins (Hoffman, M., Pratt, C. W., Brown, R. L., and Church, F. C. (1989) Blood 73, 1682-1685). One of four peptides produced when HC is degraded by neutrophil elastase has chemotactic activity for both monocytes and neutrophils with maximal migration comparable to formyl-Met-Leu-Phe, the "gold standard" bacterially derived chemotaxin. The amino-terminal sequence of this HC peptide is Asp-Phe-His-Lys-Glu-Asn-Thr-Val-... and the peptide corresponds to Asp-39 to Ile-66 of HC. A variety of synthetic peptides derived from this sequence were evaluated for leukocyte migration activity, and a dodecapeptide from Asp-49 to Tyr-60 (Asp-Trp-Ile-Pro-Glu-Gly-Glu-Glu-Asp-Asp-Asp-Tyr) was identified as the active site for leukocyte chemotactic action. The 12-mer synthetic peptide possesses significant neutrophil chemotactic action at 1 nM (60% of the maximal activity of formyl-Met-Leu-Phe), while a peptide with the reverse sequence has essentially no chemotactic activity. Cross-desensitization experiments also show that pretreatment of neutrophils with a 19-mer peptide (Asn-48 to Ile-66) greatly reduces subsequent chemotaxis to HC-neutrophil elastase proteolysis reaction products. When injected intraperitoneally in mice, the HC-neutrophil elastase digest elicits neutrophil migration. Our results demonstrate that not only does HC function as a thrombin inhibitor, but that limited proteolysis of HC near the amino terminus yields biologically active peptide(s) which might participate in inflammation and in wound healing and tissue repair processes.

Amino Acid Sequence↗

PubMed1991

On the road to mandelate ... racemase.

Explore the source record for details and available documents.

Biological Evolution↗

PubMed1991

Decrease in endothelium-dependent relaxation in the mesenteric arterial bed following vascular calcium overload produced by vitamin D3 and nicotine in rats.

Treatment of young rats with vitamin D3 plus nicotine, which has been proposed as a model of cardiovascular calcium overload, produced an increase in the calcium content of the mesenteric arterial bed and lowered in vitro vasoconstrictor responses to norepinephrine and serotonin. Attenuation of the vasoconstriction induced by norepinephrine by the endothelium-dependent vasodilators, carbachol and histamine, was diminished, but the effects of sodium nitroprusside and papaverine were unchanged. The vitamin D3 plus nicotine model may be useful for the study of the involvement of calcium overload in vascular endothelial dysfunction.

Animals↗

PubMed1991

Immunoactive products of human placenta. IV. Immunoregulatory factors obtained from cultures of human placenta inhibit in vivo local and systemic allogeneic and graft versus-host reactions in mice.

We have shown in previous reports that human placental supernatants (HPS) display a variety of immunoregulatory properties in vitro. Here we report that these supernatants are able to suppress the ability of murine splenocytes to evoke an allogeneic reaction in the popliteal lymph node (PLN) assay, as well as their capacity to induce both local (popliteal lymph node swelling) as well as systemic chronic or lethal graft-versus-host reactions. Those results are discussed in the light of the potential use of HPS in the control of transplantation immune reactions as well as in the regulation of xenogeneic pregnancies, as the murine system that was used proved that the material exerted an effect across a species barrier.

Animals↗

PubMed1991

The preparation and acute antihypertensive effects of a nanocapsular form of darodipine, a dihydropyridine calcium entry blocker.

We have addressed two problems associated with the use of dihydropyridine calcium entry blockers in antihypertensive therapy, namely, potent vasodilation and short half-lives, by incorporating the representative blocker, darodipine, into a nanocapsular vehicle. In awake, renovascular hypertensive rats, darodipine nanocapsules lowered blood pressure when given orally or intramuscularly, and the initial fall in blood pressure was less marked than that observed with the same dose of darodipine dissolved in polyethylene glycol 400 (PEG). Intramuscular administration of the nanocapsular form of darodipine had an antihypertensive effect which lasted for at least 24 hr.

Animals↗

PubMed1991

Antibody-coated erythrocytes induce secretion of tumor necrosis factor by human monocytes: a mechanism for the production of fever by incompatible transfusions.

The transfusion of incompatible red blood cells (RBC) rapidly results in the development of fever by an unknown mechanism. In this study, the human monocyte secretion of the endogenous pyrogens tumor necrosis factor (TNF) and interleukin-1 (IL-1) was measured. Exposure to human RBC sensitized with antibodies to D or Fya antigens induced the rapid secretion of TNF, but not IL-1. TNF secretion persisted when monocytes remained in contact with sensitized RBC, but returned to baseline several hours after removal of RBC. Thus, TNF secreted by monocytes may be a mediator of fever during the immune-mediated destruction of RBC in vivo.

Blood Group Incompatibility↗

PubMed1991

The effect of alpha 2 macroglobulin-proteinase complexes on macrophage Ia expression in vivo.

Alpha-2-Macroglobulin (alpha 2M) is a major plasma proteinase inhibitor. It can also regulate the function of cells of the immune system, including macrophage expression of Ia antigens in tissue culture systems. The present work was done to assess the effect of alpha 2M-trypsin complexes (alpha 2M-t) on macrophage Ia expression in vivo. Bacillus Calmette-Guerin-infected mice were injected intraperitoneally with 100nM alpha 2M-t, phosphate buffered saline (PBS), or bovine serum albumin (BSA) in PBS. The peritoneal cells were harvested by lavage from 3 to 6 days after injection. Differential cell counts were performed, and macrophage Ia antigen expression determined by indirect immunofluorescence. Injection of either alpha 2M-t or BSA solutions tended to increase the number of total cells and lymphocytes harvested, without changing the number of macrophages harvested. alpha 2M-t injection reduced the proportion of macrophages which were Ia positive from 60 to 37% on day 3 after injection, and to 20% Ia positive on day 6. The reduction in Ia positive macrophages was statistically significant when compared to either PBS or BSA injected groups. In summary, in vivo exposure to alpha 2M-t can alter macrophage function. alpha 2M-proteinase complexes formed during the course of coagulation or inflammation may play a physiologic role as regulators of the immune response.

Animals↗

PubMed1991

The consequences of aortic calcium overload following vitamin D3 plus nicotine treatment in young rats.

Treatment of young rats with vitamin D3 plus nicotine has been proposed as a model of cardiovascular calcium overload. This treatment produced a 20-35-fold increase in the calcium content of the aorta, a compliance vessel, and this increase was accompanied by a 1.6-fold elevation of pulse pressure. In aortic rings, the maximal inhibition by the endothelium-dependent vasodilator, carbachol, of vasoconstriction induced by noradrenaline decreased from 90% in controls to 61% in treated animals. There were significant correlations between aortic calcium content and pulse pressure and aortic calcium content and carbachol-induced relaxation. In conclusion, the vitamin D3 plus nicotine model may be useful for the study of the role of calcium overload in decreased arterial compliance coupled with endothelial injury.

Animals↗

PubMed1991

[Nanocapsules of beta-blocking agents: a new drug carrier in ophthalmology. Application to medical treatment of glaucoma in rabbits].

In order to reduce the lacrimal elimination and to increase the intraocular penetration of betaxolol after ocular administration, we prepared a new drug carrier, polycaprolactone nanocapsules, containing betaxolol in the base form. The instillation of nanocapsules containing only 0.1% of betaxolol into glaucomatous rabbit eyes induced a greater decrease of IOP in intensity, time and stability compared to the reduction of IOP induced after instillation of the commercial eye drops (Betoptic) containing 5 times more betaxolol (0.56%). This new pharmaceutical dosage form produces very interesting therapeutic effects with much lower drug concentrations than that commonly used in aqueous commercial eye drops; thus, systemic and local side effects could be minimized. All drugs used in medical treatments of eye diseases should be able to be included in this carrier. In addition, effective drugs not used because of their toxicity will become suitable for use at lower and safer doses.

Adrenergic beta-Antagonists↗

PubMed1991

[Indications for emergency surgical treatment of ectopic atrial tachycardia].

Recurrent automatic atrial tachycardia can induce dilated cardiomyopathy. We present clinical and therapeutic problems of 16 years old male with ectopic left atrial tachycardia refractory to pharmacological therapy. In this patient long periods of atrial tachycardia 200-240/min due to lack of effective medication caused cardiac failure. Uncontrolled taking of various antiarrhythmic drugs and persistent tachycardia led to cardiogenic shock. The electrophysiologic study revealed focus of the tachycardia localized in the area of left cardiac auricle. The rate of the tachycardia was changing from 84 to 240/min, with periods of Mobitz I block in the AV node. In periods of 1:1 AV conduction the tachycardia had sometimes LBBB QRS morphology. The atrial tachycardia provoked unsustained ventricular one. The patient was operated. Resection of left auricle and mitral valvuloplasty were performed. After the operation the patient regained undisturbed sinus rhythm and symptoms of heart failure disappeared.

Adolescent↗

PubMed1991

[Indications for emergency cardiovascular surgery at the Institute of Cardiology].

Between 1981 and 1989 73 patients (46 males, 27 females aged 15-69; mean 42) underwent emergency cardiac operation in the I Clinic of Cardiosurgery. There were 39 (53%) patients with valvular disease, 18 (25%) with prosthetic valve dysfunction and endocarditis, 9 (12%) with acute aortic dissection (2 of them had Marfan's syndrome), 5 (7%) with atrial myxoma and 2 (3%) with malignant pericardial mesothelioma. All of them were treated in C.C.U. before surgery. 27 urgent operations were performed within the first 24 hours after the admission to C.C.U. 30 of 73 patients died (41%). The IV NYHA functional class was stated as the most significant predictive factor for in-hospital mortality. The greatest mortality was observed in the group of patients with valvular disease (53%). In hospital survival rate reached 50% after reoperations as a procedure of choice in prosthetic valve dysfunction. Good early results were observed in patients with aortic dissection (survival rate--66%). The presence of Marfan's syndrome was associated with a poor surgical prognosis. There were no deaths after atrial myxoma removal, but all patients with malignant mesothelioma died. The most common cause of all deaths was congestive heart failure.

Adolescent↗