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Purpose: The objective of this study was to assess the local and systemic tolerability of two batches of the Biken acellular pertussis (Pa) vaccine following administration of a single vaccine dose to adults with or without a history of prior pertussis immunization. The results from this study were compared to data from published literature. Patients and Methods: In a controlled, open-labeled double-blind trial, 518 healthy male and female adults with or without primary pertussis immunization were enrolled at three centers. All study participants had received one single dose (0.5 ml) of the Biken two-component (23.4 mg PT; 23.4 mg FHA) Pa vaccine deeply intramuscularly. Local and systemic adverse events were solicited for 4 days using diary cards. On two occasions, between day 4–7 and between day 12–16 postvaccination, vaccinees were reexamined. At the end of the observation period (day 28) vaccinees had to send a preprinted letter to the study center indicating their state of health. Results: One serious adverse event (acute appendicitis) occurred and was considered not to be related to the study vaccine. At the injection site, redness > 20 mm was observed in one subject (0.2%), and swelling > 20 mm was seen in ten subjects (1.98%). Edematous swelling occurred in three subjects (0.59%). In 27 subjects (5.34%) a “late-onset muscle mass swelling” could be palpated, usually occurring on day 6–12 postvaccination. 429 subjects (84.78%) experienced none or only slight tenderness on pressure during the . rst 4 days postvaccination, moderate tenderness on pressure was reported by 60 subjects (11.86%) and severe tenderness by 16 vaccinees (3.16%). Systemic side effects were rare: no fever > 38.5 °C was observed, and only seven subjects (1.39%) took antipyretics. Five patients (0.99%) experienced exhaustion or nausea. The vast majority of the participants (97.43%) would opt for the vaccination again. Conclusion: The study vaccine was safe and induced only infrequently and mostly mild, local or general symptoms that all resolved spontaneously. It was well tolerated and accepted in adults.

Reaction of 1,1,1-tris(chloromethyl)ethane with ca. three equivalents of sodium or lithium (2-dimethylarsinophenyl)methylarsenide in thf gave several products including the tetra(tertiary arsine) (R_As*,R_As*)-, (R_As*,S_As*,r*)- and (R_As*,S_As*,s*)-1-(chloromethyl)-1,1-bis{[(2-dimethylarsinophenyl)methylarsino]methyl}ethane and the hexa(tertiary arsine) (R_As*,R_As*,R_As*)-1,1,1-tris{[(2-dimethylarsinophenyl)methylarsino]methyl}ethane. The latter is the first example of a chiral hexa(tertiary arsine). The products from the reaction have been separated by complexation to cobalt(III). The three diastereomers of the tetra(tertiary arsine) each bind to the metal centre in a completely stereoselective manner: the (R_As*,S_As*,r*) and (R_As*,S_As*,s*) forms of the ligand each form a single trans dichloro complex and the (R_As*,R_As*) diastereomer a cis-α complex. The structure of the latter has been confirmed by an X-ray analysis. Three other complexes have also been isolated from this reaction: trans-dichlorobis[1,2-phenylenebis(dimethylarsine)]cobalt(III) chloride, a cis-α complex of the cyclic chiral tetra(tertiary arsine) (R_As*,S_As*,R_As*)-5,6,7,8,9-pentahydro-6-{[(2-dimethylarsinophenyl)methylarsino]methyl}-1,4,6-trimethylbenzo[b][1,4]diarsacycloheptane and a cobalt(III) complex of the chiral hexa(tertiary arsine). The structures of the latter two complexes have been confirmed by X-ray analyses.

ObjectiveTo obtain normal M mode (one dimensional) echocardiographic values in a substantial sample of normal infants and children. DesignData were obtained over three years from a single centre in central Europe. Patients2036 healthy infants and children aged one day to 18 years. MethodsIn line with recommendations for standardising measurements from M mode echocardiograms, and using digital echocardiographic equipment, measurements were obtained of the following: right ventricular anterior wall thickness at end diastole, right ventricular end diastolic dimension, thickness of interventricular septum at end diastole and end systole, thickness of posterior wall of the left ventricle at end diastole and end systole, left ventricular dimension at end diastole and end systole, pulmonary and aortic valve diameter, and left atrial dimension. ResultsMeasurements are presented graphically on centile charts with respect to body surface area, and as tables with mean and 2 SD values for newborns in relation to body weight, and for infants and children in relation to body surface area. Best fitting regression equations are given for each measured variable, using the 50th centile values. ConclusionIn comparison with previously published normal values, the presented charts and tables make it possible to judge echocardiographic measurements of a particular patient as normal or abnormal.

Previously unknown metabolites from the two macrolide immunosuppressants rapamycin (sirolimus) and SDZ RAD [40-O-(2-hydroxyethyl)rapamycin] obtained after in vitro incubation with human liver microsomes have been purified. Structure elucidation was performed by nanoelectrospray ionization tandem mass spectrometry applying low energy collision activated dissociation. This ionization method is, as shown here, a powerful tool to determine metabolic pathways by analysis of even low abundance products. Product ion spectra of the isolated metabolites indicate a new kind of biotransformation reaction for rapamycin and SDZ RAD. The proposed metabolic pathway starts with an ester hydrolysis which leads to a ring-opened structure. A dehydration on C33–C34 and a supplementary hydrogenation at C33–C34 result in a structure similar to the ring-opened isomer with an single bond at C33–C34.

Uterine artery endothelial production of the potent vasodilator, prostacyclin, is greater in pregnant versus nonpregnant sheep and in whole uterine artery from intact versus ovariectomized ewes. We hypothesized that uterine artery cyclooxygenase (COX)-1 and/or COX-2 expression would be elevated during pregnancy (high estrogen and progesterone) and the follicular phase of the ovarian cycle (high estrogen/low progesterone) as compared to that in luteal phase (low estrogen/high progesterone) or in ovariectomized (low estrogen and progesterone) ewes. Uterine and systemic (omental) arteries were obtained from nonpregnant luteal-phase (LUT; n = 10), follicular-phase (FOL; n = 11), and ovariectomized (OVEX; n = 10) sheep, as well as from pregnant sheep (110–130 days gestation; term = 145 ± 3 days; n = 12). Endothelial and vascular smooth muscle (VSM) COX-1 protein levels and uterine artery endothelial cell COX-1 mRNA levels were compared. Using immunohistochemistry and Western analysis, the primary location of COX-1 protein was the endothelium; that is, we observed 2.2-fold higher COX-1 protein levels in intact versus endothelium-denuded uterine artery and a 6.1-fold higher expression in the endothelium versus VSM (P< 0.05). COX-2 protein expression was not detectable in either uterine artery endothelium or VSM. COX-1 protein levels were observed to be higher (1.5-fold those of LUT) in uterine artery endothelium from FOL versus either OVEX or LUT nonpregnant ewes (P< 0.05), with substantially higher COX-1 levels seen in pregnancy (4.8-fold those of LUT). Increases in uterine artery endothelial COX-1 protein were highly correlated to increases in the level of COX-1 mRNA (r2= 0.66; P< 0.01) for all treatment groups (n = 6–8 per group), suggesting that increased COX-1 protein levels are regulated at the level of increased COX-1 mRNA. No change in COX-1 expression was observed between groups in a systemic (omental) artery. In conclusion, COX-1 expression is specifically up-regulated in the uterine artery endothelium during high uterine blood flow states such as the follicular phase and, in particular, pregnancy.

Extraskeletal osteosarcoma (EOS) is a high grade soft tissue tumour characterised by the production of malignant osteoid, without attachment/involvement of underlying bone/periosteum. Rarely, EOS presents as a cutaneous tumour. The clinical behaviour of primary cutaneous EOS (PC-EOS) remains incompletely characterised. Herein we present the largest case series of PC-EOS reported to date. Sixteen PC-EOS cases from the archives/consultation files were retrieved (male:female 1:1; age 31–96 years, mean age 66 years). The tumours measured 1–10 cm (mean 3.2 cm) and were located on the lower extremity (7), head (6), upper extremity (2), and trunk (1). They consisted of pleomorphic, spindled-to-epithelioid cells, with fascicular, nodular, or sheet-like growth patterns and foci of malignant osteoid. Immunohistochemistry did not reveal specific lines of differentiation, and there was no evidence of other tumour types. A literature review was conducted to identify all well characterised cases of PC-EOS. A combined analysis of present and past cases was performed to determine overall trends in clinical characteristics and outcomes. The mean follow-up period was 23.9 months, during which 67.5% of patients experienced progression-free survival and 18% of patients died of disease. Rates of local recurrence and metastasis were 10% and 25%, respectively, approximately double past estimates. These data suggest that the prognosis of PC-EOS is less favourable than previously thought. The differential diagnosis includes benign entities (e.g., ossifying pyogenic granuloma) and malignant neoplasms with heterologous osteosarcomatous differentiation (e.g., carcinosarcoma, transdifferentiated melanoma). Wide excision remains the standard of care, and the role of chemotherapy and radiation remains inconclusive. Recognition of this rare entity can facilitate prompt diagnosis and appropriate treatment.

Abstract:: Mucosal epithelial cells contribute significantly to host defense mechanisms. Uroepithelial cells (UEC) from healthy donors suppress bacterial growth in vitro. Bacterial adherence to UEC has been shown to be a prerequisite. Similar results have been shown for buccal epithelial cells (BEC). The host response triggered by the host–parasite interaction seems to involve signal transduction and intracellular activation of second messengers. In this study the intraepithelial calcium flux was analyzed in individual BEC after bacterial contact. BEC were derived from scrapes of the buccal mucosa and labelled with fluo-3 (a calcium indicator). Thereafter the cells were analyzed immediately with a FACscan flowcytometer. The intracellular events were evaluated before and after the addition of viable E. coli bacteria (strain 4389, K1O1H7, pili II pos.). For control, the influence of prostaglandins, histamine, PMA, LPS and opsonized avital E. coli on the epithelial calcium flux was investigated. Additionally, supernatants of BEC-E. coli cocultures were analyzed with respect to their PgE2 content. PgE2 concentrations in supernatants of BEC, cultured alone or together with E. coli, were measured by a commercial PgE2 ELISA kit. The addition of vital E. coli to BEC was promptly answered by a significant intracellular calcium flux. PgE2, histamine and PMA, but not PgF2α, PgE1, LPS and opsonized E. coli, increased intracellular calcium. BEC alone did not release PgE2. After coculture with E. coli increased levels of PgE2 were measured in the supernatants. PgE2 release was still enhanced by coactivation of the BEC with phorbolester (PMA). Our results confirm that calcium flux in mucosal epithelial cells is stimulated by the cell–bacteria contact. We suggest that the increased PgE2 release amplifies the stimulation of intraepithelial second messengers. The resulting cell activation may lead to the secretion of antimicrobial peptides, thereby contributing to the regulation of mucosal host resistance to bacterial infections.

We address the verification problem of FIFO-channel systems. We apply the symbolic analysis principle to these systems. We represent their sets of configurations using structures called constrained queue-content decision diagrams (CQDDs) combining finite-state automata with linear arithmetical constraints on number of occurrences of symbols. We show that CQDDs allow forward and backward reachability analysis of systems with nonregular sets of configurations. Moreover, we prove that CQDDs allow to compute the exact effect of the repeated execution of any fixed cycle in the transition graph of a system. We use this fact to define a generic reachability analysis semi-algorithm parametrized by a set of cycles Θ. Given a set of configurations, this semi-algorithm performs a least fixpoint calculation to construct the set of its successors (or predecessors). At each step, this calculation is acceleratedby considering the cycles in Θ as additional “meta-transitions” in the transition graph, generalizing the approach of Boigelot and Godefroid (CAV'96, Lecture Notes in Computer Science, Vol. 1102, Springer, Berlin, 1996).

The relative configuration of a methylated undecanehexaol, a fragment of amycin B, with five chirality centers was determined by a complete ¹H and ¹³C signal assignment and interpretation of its acetonide derivatives. Copyright © 1999 John Wiley & Sons, Ltd.

The isolation of Miotoxin-A*, a novel macrocyclic trichothecene from Baccharis coridifolia DC. (Compositae) is described. The structure has been determined to be 4-hydroxy-roridin E by means of NMR-spectroscopy and X-ray structure analysis

The presence of superoxide dismutase was demonstrated in 21 strains of mollicutes, including achuloplas-mas, mycoplasmas and ureaplasmas. Additionally, catalase activities were demonstrated in nearly 50% of the cell lysates. whereas no peroxide activities were detectable. The production of O2-and H2O2 with glucose as substrate was demonstrated for 8 strains of 10 strains tested. Anaerobic mycoplasmas showed the highest amount of radical production, whereas superoxide dismutase and catalase activities were in the range of activities estimated for aerobic mollicutes. Some pathogenic strains additionally released compounds into the culture medium, which stimulated O2-production by PMNs.

This paper deals with three problems of contemporary behaviorism: the problem of the triviality of the Law of Effect; the problem of formalisation; and the problem of axiomatisation. As to the first problem a nontrivial version of the Law of Effect dating back to the early 1950s is reproduced and used to show that the versions offered today, besides being tautological (or methodologically unacceptable on other grounds), do not even answer a standard allowing them to compete with what was achieved already 25 years ago. The second and the third problem arise in connection with attempts to render the hypotheses of behaviourism more precise and to clarify their interrelations. Up to now efforts in this field have not produced much but pseudoprecision. What has been achieved by formalisation hardly exceeds mere translation from vague ordinary into vague formal statements. And in axiomatisation assertions rather than proofs of deducibility relations prevail. Since these defects are hidden behind a pretentious technical apparatus, however, it is to be feared that they will be neglected. And behaviourism thus risks to overestimate by far its level of theory formulation.

The conversion of euphorianin to deacetyldehydroeuphorianin which was used in an X-ray crystal structure analysis is described. A new pentacyclic structure related to ingol tetraacetate is described for euphorianin.

Summary Replication of pseudorabies virus (PrV) in Chinese hamster ovary (CHO) cells, a cell line naturally resistant to infection by herpesviruses, is blocked at the level of penetration. Virions bound to the surface of CHO cells are taken up into cytoplasmic vesicles and degraded.

Summary Neutralization of poliovirus type 1 was studied using radioactively labelled polyclonal IgG. With nonsaturating antibody concentrations various virus-antibody complexes were produced which were isolated by sucrose gradient centrifugation and identified by electron microscopy as virus monomers, dimers, trimers, tetramers and pentamers. The neutralization rate (n. r.) of each of the virus-antibody complexes relative to non-neutralized virus and the stoichiometry have been estimated. The monomer fraction showed that about every fifth virion was associated with one IgG molecule and neutralized. The antibody was bivalently attached. The majority of virus particles formed aggregates of different sizes, which were cross-linked by antibodies. The following neutralization rates and ratios of IgG to virus (IgG/V) were determined for the oligomers: dimers, 59.2 per cent n. r. and 0.55 IgG/V; trimers, 67.3 per cent n. r. and 0.66 IgG/V; tetramers, 79.0 per cent n. r. and 0.75 IgG/V; pentamers, 86.3 per cent n. r. and 0.98 IgG/V.

Summary The aim of the study was to evaluate a new ELISA for detection of HIV-1, HIV-2 and HIV-1 subtype 0 (HIV-0) antibodies. The assay format is based on the antigen sandwich principle. To enable specific detection of HIV-0 antibodies, in addition to HIV-1 and HIV-2 antigens HIV-0 antigen is used for coating the solid phase and for the conjugate. The results show that all 12 HIV-0 samples tested were detected with a high degree of reactivity, as were all the 1,144 anti-HIV-1 and 424 anti-HIV-2 positive samples. The capacity of the test to enable early detection of seroconversions is equivalent to that of other sandwich ELISAs. The specificity of the assay was determined to be 99.89/99.94% (initial/after retest) using 58,366 samples, which is superior to the other ELISAs used for comparison. Even with difficult samples (i.e. samples of African origin, samples known to cause false-positive reactivity in different ELISAs, or samples containing potential interference factors) there were very few false-positive reactions. Therefore, the new assay is well suited for screening blood donations as well as for evaluating samples from patients of different geographic origin.

The alcoholysis of epoxide 1 in acidic methanol leads to various products; one of these — hydroxymethoxyketone 7 — rearranges to the isomeric ketone 14 on contact with silica gel.

Secondary enaminones 2 are easily halogenated to yield the so far unknown halogenides 3,4 and 5. Acyloxylation of enaminones 2 by dibenzoylperoxide leads to benzoyloxylated substances 13, which also have not been described jet. Bisacylated products could not be traced. Only the rearranged compounds 14 could be isolated. 14b showed cytotoxic activity.

By means of 2D NMR experiments (COSY, HMQC, HMBC, ROESY), the constitution of the photoreaction product 3-deoxo-1α,3 α-diacetoxy-1,2,3,3,8,30-hexahydro-18βH-andirobin (2), obtained by photolysis of 7-deacetoxy-7-oxokhivorin (1) in methanol, was shown to be a ring B seco-limonoid with the 14,15-epoxide intact. The configuration of C-8 is R. Ring C adopts a twist-boat conformation. No conformational preferences for the rotation of ring A in 2 with respect to rings C/D and for the side-chain C-6/C-7 could be detected. Nearly all ¹H and all ¹³C resonances were assigned unambiguously. © 1998 John Wiley & Sons, Ltd.

Roseanolone is a new diterpene from the African plant Hypoestes rosea (Acanthaceae). The isolation is described; the structure has been determined to be 1,2,3,3a,4,5,6,6a,7,8,9,10a-dodecahydro-5-hydroxy-3-isopropyl-3a, 6-oxa-6,9,10a-trimethyl-dicyclopenta[a,d] cycloocten-1-one by X-ray crystallography.

The rearrangement of 3-oxo-14β-hydroxy-12β-methanesulfoxy-card-20(22)-enolide and 14β-hydroxy-12β-methanesulfoxy-pregnane-3,20-dione during elimination of the sulfoxygroups was studied. By means of 2D-NMR analysis the structures were determined as 13,17-seco-12,17-cyclo-steroids.

Three triterpenoids have for the first time been isolated from fresh undried jute root, ursolic acid as its acetate, corosolic acid as its acetate and indicated to be urs-2a,2β-diol-12-en-28-oic-acid and oxo-corosin isolated as its acetate-methyl-ester, C36H54O10, m.p. 160 °C, aD-15° (c 0.435%). The 24-carboxyl in corosin-anhydro-lactone-acetate has been reduced to the methyl group and the resultant lactone on acetylation indicated to be identical with tormentic acid lactone acetate.

Zusammenfassung An 328 Steinwildschädeln aus allen Teilen Graubündens wurde eine Altersbeurteilung durchgeführt. Als geeignet erwiesen sich hierfür der Durchbruch und der Wechsel der Zähne, die Abnutzung der Schneide- und Backenzähne sowie die Altersmerkmale an den Hörnern (Hornlänge, Jahresfurchen und Schmuckknoten).

Die drei gebräuchlichsten Methoden der Altersbestimmung beim Rotfuchs (Zahnabnutzung, Linsentrockengewichts- und Zementzonenbestimmung) wurden an einem Material von 25 Tieren vergleichend getestet. Hierbei ergab sich für alle Altersstufen lediglich zwischen Zahnabnutzung und Zementringbestimmung eine gute Übereinstimmung, so daß für populations-dynamische Untersuchungen die Altersschätzung nach den Abnutzungserscheinungen am Gebiß als völlig ausreichend erscheint. In zweifelhaflen Fällen und für wissenschaftliche Untersuchungen ist der etwas zeit- und materialaufwendigeren Zementringmethode der Vorzug zu geben, wobei Horizontalschnitte durch die Wurzelspitze der mittleren Prämolaren (P2u. P3) zu besonders guten Ergebnissen führen. The three most useful methods of determining the age of the red fox (tooth wear, dry weight of the crystalline lens, cementum layers) were tested out on a group of 25 animals. For all age classes, there was a close correspondance between the first and third methods, so that it would appear entirely satisfactory for investigations into population dynamics to estimate age on the basis of signs of dental wear. In cases of doubt and for scientific experiments, the cementum ring method, though somewhat more costly as regards time and materials, is to be favoured: horizontal crosssections of the root tips of the middle premolars (P2and P3) give extremely good results. Les trois méthodes les plus usuelles de détermination de l'âge chez le Renard (attrition, poids des cristallins et relevé de zones de cément) font l'objet d'une analyse comparative au moyen d'un matériel constitué de 25 animaux. Ce n'est qu'entre le degré d'attrition et le nombre de cernes de cément qu'une bonne concordance fut obtenue pour toutes les classes d'âge, de telle sorte que, pour des recherches sur la dynamique des populations, l'estimation de l'âge d'après le degré d'attrition du maxillaire apparaît comme tout à fait satisfaisante. Dans les cas douteux et pour les besoins de recherches scientifiques, la méthode des cernes de cément, plus exigeante en temps et en matériel, est à préférer. Il est à signaler à cet égard que les coupes horizontales à travers les extrémités des racines des prémolaires intermédiaires (P2et P3) livrent des résultats particulièrement bons.

An investigation was made of the sensitivity and specificity of four-layer radio-immunoassays (RIA) in the detection of adenovirus, respiratory syncytial virus, influenza virus types A and B, as well as para-influenza virus types 1, 2 and 3 from nasopharyngeal aspirates of 146 patients with acute respiratory disease. The sensivity of RIA was comparable with that of tissue culture isolation if the total number of positives is considered. The difference may have been caused both by a higher efficiency of the RIA for detection of inactivated or non-cultivable agents and by a higher efficiency of tissue culture methods if the samples contained only small amounts of antigen. Differences between the two antigen detection systems were found in particular with respiratory syncytial virus and influenza B virus. At present, the use of tissue culture isolation together with RIA is the optimal routine laboratory procedure for the diagnosis of respiratory infections.

Human fibroblasts in primary culture released reactive oxygen species upon exposure to synovial fluid obtained by joint aspiration from twelve patients suffering from rheumatoid arthritis. The primary radical produced was O-2 as determined by ESR spin trapping and cytochrome c reduction. In contrast to the oxidative burst in granulocytes and monocytes. radical formation proceeded continuously for at least four hours.Low-level chemiluminescence was increased upon exposure to inflammatory human synovial fluids. Spectral characteristics and effects of azide and 1,4-diazabicyclo-(2,2,2)-octane led to the conclusion that the photoemissive species were excited carbonyls. Radical production and light emission were not altered either by xanthine or allopurinol. nor by azide. cyanide or rotenone. The O-2; production increased in the presence of NADH or NADPH. making an NAD(P)H oxidase a likely source.The liberation of reactive oxygen species correlated with the number of leukocytes present in the inflammatory joint fluids. but not with the concentrations of immunoglobulins and complement factor C3.

The two types of herpes simplex virus (HSV-1, HSV-2) induced significantly different alterations in the morphology and permeability of infected cells. HEp-2 cells infected with HSV-1 (strain THEA) were characterized by the formation of polynuclear syncytia. In contrast, after infection with HSV-2 (strain D316, DD), the cells were rounded up. The HSV-1 strains KOS and LS5039 and the HSV-2 strain 196 induced both types of cytopathic effect. As shown by comparative scanning and transmission electron microscopy newly synthesized virus particles of the various strains of HSV-1 were generally found to be restricted to smooth areas of the cell surface. In these areas the number of microvilli was reduced in comparison to uninfected cells. However, the progeny viruses of the strains of HSV-2 were mainly connected with protrusions of the cell membrane (microvilli and filopodia).

To assess whether pharmacologic coronary vasodilation could provoke new left ventricular wall motion abnormalities in patients with single vessel coronary artery disease, systemic hemodynamics, coronary blood flow velocity and left ventricular wall motion were measured by two-dimensional echocardiography during administration of 10 mg of intracoronary papaverine in 14 patients before and again immediately after left coronary angioplasty (group 1). As a comparison with an intravenous method, left ventricplar wall motion was analyzed after 0.56 mg/kg body weight of intravenous dipyridamole in a separate group of 13 patients with single vessel coronary disease (group 2). Heart rate-blood pressure product increased 3% to 6% in papaverine-treated patients and 14 ± 11% (p = NS) in dipyridamole-treated patients. No angiographic collateral vessels were present in either group.

The kallikrein inhibitor-peptide content of Tityus serrulatusscorpion crude venom was purified by Sephadex G-50 and Sephadex G-25 fine gel filtration chromatographies, followed by two steps of reverse-phase column on HPLC. The isolated inhibitor peptide was homogeneous in its N-terminal and partial amino acid sequence, showing a molecular weight of 4.489 Da by mass spectrometry and amino acid analysis. The peptide was tested with rat plasma and urine kallikrein, which resulting in an inhibition with similar afinity to both enzymes, showing an IC50of 14.3 μM after 13 and 8 min, respectively, using kininogen as substrate on the isolated guinea-pig ileum bioassay. The porcine pancreatic kallikrein showed after 10 min an IC50value of 12.6 μM with H-D-Val-Leu-Arg-pNA HCl as substrate. In addition, the isolated peptide significantly inhibited porcine pancreatic kallikrein with values in the range of apparent or absolute calculated peptide Ki= 2.5 μM. The inhibitor was heat resistant and stable at pH values less than 5.

In the course of systematic investigations on low-molecular-weight compounds from the venom of Crotalidae and Viperidae, we have isolated and characterized at least three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedivenom by gel filtration on Sephadex G-25 M, Sephadex G-10 followed by HPLC. The peptides showed bradykinin-potentiating action on isolated guinea-pig ileum, for which the BPP-V was more active than of BPP-II, and BPP-III, rat arterial blood pressure, and a relevant angiotensin-converting enzyme (ACE) competitive inhibiting activity. The kinetic studies showed a Kiof the order of 9.7 × 10−3μM to BPP-II, 7 × 10−3μM to BPP-III, and 3.3 ×10−3μM to BPP-V. The amino acid sequence of the BPP-III has been determined to be pGlu-Gly-Gly-Trp-Pro-Arg-Pro-Gly-Pro-Glu-Ile-Pro-Pro, and the amino acid compositions of the BPP-II and BPP-V by amino acid analysis were 2Glu-2Gly-1Arg-4Pro-lIle and 2Glu-2Gly-lSer-3Pro-2Val-Ille, with molecular weight of 1372, 1046, and 1078, respectively.