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.     

GONADAL DYSFUNCTION IN PATIENTS WITH ATAXIA TELANGIECTASIA

ABSTRACT. Two males and three females with ataxia telangiectasia aged from 4 6/12; to 23 years were subjected to an i.v. LH-RH test. All were found to have elevated basal levels of FSH and three had elevated basal levels of LH. In all the response of FSH to LH-RH was supranormal. In the pubertal and adult females the basal levels of estradiol were low. The laboratory and clinical findings in these patients as well as data reported by others indicate that the primary gonadal failure is an integral part of AT.     

GONADAL FUNCTION IN BLOOM''S SYNDROME

Five patients with Bloom's syndrome aged from 2 8/12 to 27 years, all of whom had hypogonadism, were subjected to an i.v. LHRH test and two of them to an i.m. HCG test. There was increased responsiveness of plasma LH and FSH, indicating that the hypogonadism is primary in nature and of early development. The tubular element of the testis seems to be mainly affected, as indicated by the particularly high FSH response to LHRH stimulation, a history of sterility in the two adult patients and documented azoospermia in one of them. The Leydig cells seem to be less affected and secrete sufficient androgens to enable puberty within acceptable normal limits. Hypogonadism seems to be a major characteristic of Bloom's syndrome.     

PLASMA GLUCAGON RESPONSE TO ARGININE INFUSION IN CHILDREN AND ADOLESCENTS WITH DIABETES MELLITUS

Plasma glucagon response to an arginine infusion was studied in children and adolescents belonging to the following groups: (I) twenty-two controls; (II) six subjects with delayed insulin peak during oral GTT; (III) ten diabetics on diet and/or oral therapy; (IV) six newly diagnosed uncompensated diabetics; and (V) eight diabetics on insulin therapy. The fasting glucagon concentrations and rise of glucagon in response to arginine in the patients of Groups II, III and V were similar to those of the controls (Group I). The basal levels and rise of glucagon in the newly diagnosed, uncompensated dibetic children (Group IV) was elevated compared to the other groups but the difference was statistically not significant. The results of this investigation favour the hypothesis that the hyperglucagonaemia in diabetes is a secondary effect to the metabolic derangement, bearing a direct relationship to the degree of homeostastic decompensation.     

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.     

PROLACTIN SECRETION IN GIRLS WITH ISOLATED GONADOTROPHIN DEFICIENCY

Plasma prolactin, basal levels and the response to an i.v. injection of TRH (100 microgram/m2) was determined in five girls with isolated gonadotrophin deficiency of hypothalamic origin before and after at least 3 months cyclic replacement therapy with conjugated oestrogens (1.25 mg/day). The basal plasma prolactin levels were similar during both tests, however, during oestrogen therapy the mean peak response to TRH almost doubled and the sum of all the values obtained (basal, +15, +30 and +60 min) was significantly higher. It is of note that even upon prolonged oestrogen deprivation the releasable prolactin response to TRH was adequate.     

DIFFERENTIAL DIAGNOSIS BETWEEN HYPOTHALAMIC AND PITUITARY hGH DEFICIENCY WITH THE AID OF SYNTHETIC GH-RH 1–44

Synthetic GH-RH 1–44 administered as an intravenous bolus (1 μg/kg) evoked a marked hGH rise (>20 ng/ml) in three children with constitutional short stature and in two of eight children diagnosed as having hGH deficiency by insulin hypoglycaemia and/or clonidine tests. As judged by the intensity of the hGH response to the dose employed and the peak time, GH-RH 1–44 may be as potent as GH-RH 1–40 in children. It is concluded that GH-RH is an important addition to the endocrine armamentarium, providing the means for differentiation between hypothalamic and pituiary hGH deficiency in a simple test which is devoid of side effects.     

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.