Synthesis and biological activity of Substance P C-terminal hexapeptide and heptapeptide analogues

The analogues [Glu(OBzl)¹¹]SP_6–11 and [Glu(OBzl)¹¹]SP_5–11 of the C-terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the SCH₃ group of Met¹¹ is replaced by the COOCH₂C₆H₅ group. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD), and rat portal vein (RPV). The selectivity for the different receptors has been studied by utilizing atropine-treated guinea pig ileum (GPI + At). The results showed that both analogues are mainly active on GPI through the NK-1 receptor and that both analogues are equipotent to Substance P.     

Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0.12 µg. kg^–1 in two animalsand 0.6 µg. kg^–1 in four) was incorporated intothe beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0.008) reducedin the control group (0.58± 0.38 vs 3.42 ± 0.84),in contrast to nearly baseline values in the experimental group(0.58 ± 0.33 vs 1.17 ± 0.42, P=0.41). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0.04). Tissue samples fromboth groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0.04) higher in the peri-infarctregion of the experimental group, as compared with controls(106.5 ± 2.8 vs 92 ± 4.4 gray level units). Microvesselsstained for von-Willebrand factor were similar in nwnber inboth groups (P=0.8), as were mesenchymal cells stained for vimentin(P=0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth.     

Multivariate Analysis of Left Ventricular Mass Determinants in Adults

Echocardiographic left ventricular mass (LVM) estimates are strong predictors of subsequent mortality and cardiovascular events. It is known that blood pressure (BP), weight (WT), and age are significantly correlated with LVM. We hypothesized that stroke volume (SV) measured by Doppler echocardiography would also be correlated with LVM. Two hundred and thirteen patients referred for routine echocardiography had determination of LVM, cuff BP, and Doppler SV. Those with localized LV disease, valvular disease, or cor pulmonale were excluded. In both men and women, systolic BP (SBP) was more closely correlated with LVM than was diastolic blood pressure or mean arterial pressure, and SV was more closely correlated with LVM than cardiac output or cardiac index. Stepwise regression, followed by multiple regression showed that four variables (WT, SV, SBP, and AGE) explained 32.3% of the variability in LVM in men and 48.5% of the variability in LVM in women. WT and SV were significant determinants of LVM in both men and women. Age was also significant in men and SBP was also significant in women. For both men and women, SV was more significantly correlated with LVM than was SBP. The changes in LVM associated with 1 SD increments of SV and SBP, respectively, were 8 and 5 g for men and 13 and 11 g for women. We conclude that men and women have different patterns of variables influencing LVM. Doppler echocardiographic SV is a newly described determinant of LVM that has a greater correlation with LVM than does SBP. This study reemphasizes the importance of WT as the major determinant of LVM.     

INHIBITION OF PORCINE ELASTASE II BY CHICKEN OVOINHIBITOR

Interaction of porcine elastase II with native and modified chicken egg-white ovoinhibitor was studied by determining the residual activity of the partially inhibited enzyme and by direct measurement of the stoichiometry of interaction using affinity chromatography, electrophoresis and gel filtration. It was found that the chymotrypsin binding site that is not modified by mild oxidation with N-chlorosuccinimide (Shechter et al., Biochemistry, (1977) 16, 992–997) is capable of binding elastase II as well. The binding of chymotrypsin and elastase II is mutually exclusive and the affinity for chymotrypsin is stronger. Binding of 2 mol trypsin as 1 mol elastase I by ovoinhibitor does not interfere with the binding of elastase II. There is also an indication that the second binding site for chymotrypsin is capable of forming a complex with an additional molecule of elastase II, but the binding is so weak that it could be detected only by electrophoresis.     

Diagnosis and treatment of accidental root perforations

A review of endodontic and periodontal aspects on the prognosis, diagnosis, prevention, and treatment of accidental root perforations is presented. Successful treatment depends mainly on proper diagnosis and immediate sealing of the perforation to eliminate risk of infection. A classification of root perforations is presented in the review to assist the clinician in making a proper choice of treatment protocol.     

Partial amino acid sequence of porcine elastase II

The partial amino acid sequence of porcine elastase II, isolated from crude trypsin Type II, was determined. The enzyme consists of two polypeptide chains, a light chain composed of 11 residues, and a heavy chain (M_r = 23 500) with four intrachain disulfide bridges; the two chains are held together by one interchain disulfide bond. Elastase II was fragmented into several peptides by chemical cleavages with CNBr at the two methionine residues, 99 and 180 (chymotrypsinogen numbering), and with hydroxylamine at the peptide bond following DIP-Ser¹⁹⁵. About 50% of the sequence was determined and the positions of 120 amino acids were located, including the light chain residues and most of the active site residues. The partial sequence shows 64% difference between porcine elastase II and elastase I and only 26% difference between porcine elastase II and bovine chymotrypsin B.     

LOCAL MICROWAVE HYPERTHERMIA AND INTRAVESICAL CHEMOTHERAPY AS BLADDER SPARING TREATMENT FOR SELECT MULTIFOCAL AND UNRESECTABLE SUPERFICIAL BLADDER TUMORS

Purpose

The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neodjuvant organ sparing clinical study.

Materials and Methods

A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system,* based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas.*Boston Scientific Corp., Natick, Massachusetts.

Results

After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved.

Conclusions

Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.     

Short-Term Thrombosis after Transvenous Permanent Pacemaker Insertion

In order to assess prospectively the incidence and significance of venous thrombosis early after permanent transvenous pacemaker implantation venographic studies were carried out in 40 consecutive patients. The venograms performed between 1 and 6 months (mean 4 months) after the implantation were normal in 31 patients (77%), in six patients (15%) they showed partial venous obstruction and in three patients (8%) total obstruction. Between 6 and 12 months (mean 9 months) the venograms of five patients, that were previously normal, showed partial venous thrombosis. No changes were found in the venograms performed later. Only two of 14 patients with thrombosis of the great veins was clinically symptomatic and developed arm edema, that resolved spontaneously within about a month. No difference in incidence of abnormal venograms was found according to the type of insulation, the polarity of the electrode and the route of entry.     

TRANSVERSE MYELITIS FOLLOWING MUMPS

An example of transverse myelitis complicating seriologically proven mumps in a 3-year-old boy is described. This patient is the youngest as yet reported with the condition.