We synthesized peptides of the general formula Argn, Lysn, and (Lys-Arg)n. These agents inhibited the ristocetin-mediated binding of vWF to GPIb and the binding of asialo-vWF to platelets. This inhibitory activity was proportional to the number of lysine and/or arginine residues/molecules present. Peptides to which the sequence of Arg-Gly-Asp-Val (RGDV) had been added at the carboxy-terminus of (Lys-Arg)n, Lysn, or Argn also inhibited vWF binding. Peptides with an RGDV sequence were found to block the binding of 125I-fibrinogen to ADP-stimulated platelets. These findings indicate that the general formulae (Lys-Arg)n, Lysn, and Argn with an RGDV sequence inhibit the binding of fibrinogen to activated platelets as well as the binding of vWF to GPIb. Thus, these peptides may behave as bifunctional antiplatelet agents.

Amino Acid Sequence↗

PubMedDate not supplied

The role of the RGD peptides and the gamma chain peptide of fibrinogen on fibrinogen binding to activated platelets.

The interaction of fibrinogen with platelet membrane glycoprotein (GP) IIb/IIIa complex is inhibited by the RGD peptides and the peptides corresponding to a sequence unique to fibrinogen in the carboxyl-terminal domain of the gamma chain. The present study was designed to examine the effects of these synthetic peptides on fibrinogen binding to thrombin-activated platelets. The order of potency of these peptides was as follows: RGDS = RGDF > GQQHHLGGAKQAGDV (G15). The RGES peptide had no inhibitory activity. The inhibitory effects of the peptides were synergistic when fibrinogen binding was measured in the mixture of the RGD peptide and the gamma chain peptide. By contrast, the inhibitory effect was additive when the binding was measured in the presence of the RGDS peptide and the RGDF peptide. Thrombin-induced platelet aggregation was also inhibited by these synthetic peptides. The order of potency was the same as that of the inhibition binding assay. These results provide evidence that the RGD sequences present at two different sites in the alpha chain and the gamma chain sequence inhibit fibrinogen binding to the GPIIb/IIIa complex, are mutually exclusive, and are in close spatial proximity in the folded molecule. We conclude that the presence of the RGD sequence and the gamma chain sequence involved in fibrinogen binding domains increases the affinity of fibrinogen to activated platelets.

Amino Acid Sequence↗

PubMedDate not supplied

Effect of cyclic Arg-Gly-Asp-containing peptide on fibronectin binding to activated platelets; role of fibronectin on platelet aggregation.

The interaction of fibronectin with glycoprotein IIb/IIIa (GPIIb/IIIa) was studied. Fibronectin bound to thrombin-stimulated platelets in a calcium-dependent, specific, and saturable manner with 98,000 molecules/platelet (Kd = 2.76 x 10(-7) M). The binding was inhibited by other adhesive proteins with IC50S of 0.076-0.105 microM and the anti-GPIIb/IIIa monoclonal antibody (LJ-CP8). The binding was also inhibited by the cyclic GRGDSPA peptide and the linear GRGDSPA peptide with IC50S of 0.223 microM and 3.75 microM, respectively. Native fibronectin, the cyclic peptide, and the linear peptide blocked thrombin-induced aggregation with IC50 of 0.95 microM, 32 microM, and 190 microM, respectively. These observations imply that the conformation of RGD-containing sequence may play an important role for an increasing affinity of the binding, and fibronectin may prevent thrombus formation by interfering with the interaction between fibrinogen and activated GPIIb/IIIa.

Amino Acid Sequence↗

PubMedDate not supplied

Right ventricular failure during clinical use of a left ventricular assist device.

The purpose of this study is to describe the authors' clinical experience of RVF during LVAD pumping and to delineate the effect of LVADs on RV function, with special reference to the level of myocardial recovery. Pneumatically driven LVADs were used on a total of 13 postoperative cases for 18 hours to 70 days (mean, 9.9 days). The RVF, which was defined as increased right atrial pressure (RAP greater than or equal to 20 mmHg) during LVAD pumping, were experienced in four cases (two ischemic, two valvular). Duration of the RVF ranged from 3 hours to 8 days (mean, 3.0 days) and the maximum RAP ranged 22-30 mmHg (mean, 27 mmHg). The effects of LVAD pumping on the RV function were delineated during serial pump on-pump off studies in two cases with RVF and three cases without RVF, in relation to off/on ratio of the systolic aortic pressure (AOP off/on), which worked as an indicative parameter of myocardial recovery. Each pair of on/off data were assigned to four groups according to AOP off/on and complication with RVF, and mean percentage changes of mRAP and PAP were compared. The RAP of RVF cases were significantly increased by 16% with the LVAD pumping when the AOP off/on was below 0.7, whereas PAP invariably decreased in most cases. The results indicated that the LVAD suppressed the RV function before the myocardial recovery and when the heart was complicated with RVF.

Equipment Design↗

PubMedDate not supplied

Spermicidal activity of menfegol-coated condom.

The spermicidal activity of menfegol-coated condoms was investigated. Menfegol (P-menthanyl-phenyl-polyxyethylene [8,8] ether) showed strong spermicidal activity at 0.5 mg/ml and higher concentrations. Semen was ejaculated directly into menfegol-coated condoms (20 mg/condom) or uncoated condoms. Immediately after ejaculation, sperm motility and viability were examined. In the menfegol-coated condoms, sperm motility was completely suppressed and no viable sperm were observed. In the uncoated condoms, most of the sperm were alive, although their motility was almost suppressed. These results indicate that the menfegol-coated condom represents a new birth control method in which the contraceptive efficacy of the condom is enhanced by the spermicidal activity of menfegol.

Contraceptive Devices, Male↗

PubMedDate not supplied

Two cases of Pneumocystis carinii pneumonia occurred in human immunodeficiency virus infected patients: supplemental treatment with aerosolised pentamidine isethionate.

Two cases of Pneumocystis carinii pneumonia occurred in human immunodeficiency virus infected patients who were diagnosed by the aspiration-lung-biopsy. They were treated with 4 mg/kg of pentamidine isethionate intravenously administered followed by pentamidine aerosol inhalation. Although clinical and laboratory findings were improved by the fifth or seventh day of intravenous therapy, substantial leukocytopenia, from 3,000/cmm to 600/cmm and from 2,700/cmm to 1,000/cmm, occurred. At this point, the method of pentamidine administration was switched to inhalation. Pentamidine 600 mg in 30 ml distilled water was aerosolised using ultrasonic nebuliser and exposed for a 30-minute period once daily. In both cases, chest x-rays showed improvements: The disappearance of P. carinii were obtained in two weeks. Mild coughing was the sole adverse reaction encountered during the course of aerosol inhalation.

Administration, Inhalation↗

PubMedDate not supplied

Three cases of acquired immunodeficiency syndrome complicated with toxic epidermal necrolysis.

Co-trimoxazole (trimethoprim-sulfamethoxazole) and pyrimethamine-sulfadoxine have been recommended for treatment and prophylaxis, respectively, of Pneumocystis carinii pneumonia (PCP). However, toxic epidermal necrolysis (TEN) occurred in three of four patients with acquired immunodeficiency syndrome (AIDS) during the course of treatment or prophylaxis of PCP with these agents. On the other hand, 14 patients with PCP treated with pentamidine never developed TEN. Because the incidence of adverse skin reactions is higher among patients with AIDS than those without AIDS, and TEN is a severe, potentially fatal skin reaction, sulfonamide-containing drugs should be given cautiously to patients with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Microencapsulation of pheromone-analogue and measurement of the sustained release.

A model study was conducted to establish 2 feasible production and application systems for the long-term, sustained release of pheromone into the atmosphere of targeted areas. The desired goal of effective release was set at least half a year. 2-Ethylhexyl acetate (EHA) was selected as a pheromone analogue due to its similar structure and easier access for quantitative analysis. At first EHA was impregnated in wax particles, which were then encapsulated employing the complex coacervation of a gelatin-gum arabic system. The release period of EHA through the gelatin wall, however, turned out to be too short--only a week at most. As a second attempt, a modification of the two-phase emulsion technique was employed to encapsulate multiple numbers of wax particles in hydrated networks of gelatin. Though the initial release rate of EHA was still too high, 60 per cent of encapsulated EHA underwent sustained release over six months after absorbed moisture had completely evaporated. A two-step mechanism of mass transfer was proposed and the related parameters in terms of the capacity coefficient and effective diffusion coefficient were estimated.

Acetates↗

PubMedDate not supplied

Hemodynamic performance in a heterotopically transplanted dog heart: proposal of techniques for working left heart model of heterotopic (abdominal) heart transplantation.

To study hemodynamics together with various aspects of rejection after experimental heart transplantation, we developed a technique to produce a working left heart model of heterotopic (abdominal) heart transplantation. The interatrial septum and tricuspid valve of the donor heart are removed. The pulmonary arterial trunk, pulmonary veins, and inferior vena cava are ligated, and the stumps of the donor aorta and superior vena cava are anastomosed in an end-to-side fashion to the recipient abdominal aorta and inferior vena cava, respectively. Arterial blood from the recipient abdominal aorta thus perfuses the donor myocardium through the coronary artery, and the donor left ventricle receives venous blood from the recipient inferior vena cava as preload. In this model, the donor left ventricle does not pump out enough venous blood to desaturate the recipient femoral arterial blood but does generate approximately the same pressure as the recipient's heart. This model is reproducible, easy to manage, and can be applied to heterotopic heart transplantation in various experimental animals including rats.

Abdomen↗

PubMedDate not supplied

Surgical treatment for isolated hypoplasia of the right ventricle.

Four patients with isolated hypoplasia of the right ventricle who underwent intracardiac repair are described. An atrial septal defect (ASD) was successfully closed in 3 patients with mild hypoplasia of the right ventricle. The remaining patients underwent ASD closure and right atrium-to-pulmonary artery connection with a conduit with a bovine pericardial valve because of severe hypoplasia of the right ventricle and tricuspid valve. Postoperative angiocardiogram in the last patient demonstrated two-channel pathways from the right atrium to the pulmonary artery via both the right ventricle and external conduit. At long-term follow-up studies, 3 patients had developed arrhythmias and/or sinus node dysfunction, and one had died, probably because of arrhythmia, 13 years postoperatively. The right ventricular ejection fractions were below normal levels at 11 and 12 years postoperatively in 2 patients who underwent closure of ASD. It was concluded that the mild form of hypoplasia of the right ventricle should be surgically corrected by ASD closure, while right atrium-to-pulmonary artery connection or Fontan's operation should be chosen for cases of severe hypoplasia. Arrhythmias and hypofunction of the right ventricle are long-term problems after intracardiac repair of this anomaly.

Adolescent↗