Photolysis and ozonolysis of (iso) desmosine-containing crosslinked peptides from porcine aorta elastin

This report describes the use of photolysis and ozonolysis as a means of achieving complete cleavage of the pyridinium ring of (iso)desmosine in crosslinked elastin peptides. Although photolysis leads to the opening of the ring with concomitant formation of lysine, the peptide chains remain attached. Subsequent ozonolysis is able to completely achieve the cleavage of the rest of the ring skeleton, thus leading to the separation of the peptide chains. Formation of new amino acids, i.e. α-aminoadipic and glutamic acids, is emphasized. Localization of these amino acids within the released peptides should be of help in structural investigations on the crosslinking zones involving either isodesmosine or desmosine. However, other amino acids such as tyrosine and phenylalanine are sensitive to this procedure and side reactions occur which are responsible for peptide bond cleavage with the formation of breakdown products.     

Surgical Excision versus Curettage plus Cryosurgery in the Treatment of Basal Cell Carcinoma

BACKGROUND: Both cryosurgery, with and without prior curettage, and surgical excision (SE) are common therapeutic strategies for basal cell carcinoma (BCC). OBJECTIVE: The objective was to compare the efficacy between curettage plus cryosurgery (C&C) and SE in nonaggressive BCC of the head and neck. MATERIALS AND METHODS: A randomized controlled trial was carried out, in which tumors were assigned to either C&C (n=51) or SE (n=49). C&C was performed with a double freeze-thaw cycle after prior curettage of the tumor. SE was performed with a margin of 3 mm and with delayed histologic examination. RESULTS: Recurrences occurred 9 times after C&C (17.6%) and 4 times after SE (8.2%). The overall 5-year recurrence probability was 19.6% for C&C and 8.4% for SE (p=.10). A hazard ratio of 2.57 (95% CI, 0.79-8.34) indicated a putative, but not statistically significant, advantage of SE. CONCLUSION: These data reflect the outcome of the first randomized controlled trial with long-term follow-up in the treatment of BCC, comparing C&C with SE. Although not statistically significantly different, the observed differences could still be of clinical relevance. Owing to the trend toward lower recurrence rates, better cosmetic results, and reduced wound healing time, we believe that SE should be preferred to C&C in the treatment of primary, nonaggressive BCC of the head and neck.     

Job stress, absenteeism and coronary heart disease European cooperative study (the JACE study): Design of a multicentre prospective study

Background: The motives, objectives and design of a multicentreprospective study on job stress, absenteeism and coronary heartdisease in Europe (the JACE study) is presented in this paper.Some specific gaps in the reviewed literature are explicitlytapped into by the JACE study. Its objectives are i) to comparethe distributions of the Karasek job stress scales for the samebroad categories of occupations in different European countries(in males and females), ii) to study the predictive power ofthe job stress scales and the job strain model for one yearof sickness absence (in males and females) and iii) to studythe predictive power of the job stress scales and the job strainmodel for a three year incidence of coronary heart disease (Inmales only). Methods: In answering these questions, relationsare studied controlling for gender, age, level of education,company size, physical work risks and shift work, as well astraditional risk factors for CHD (i.e serum cholesterol, serumHDL cholesterol, smoking habits and blood pressure). The JACEstudy is a Biomed 1 concerted action. The JACE group consistsof eight participating centres from six countries, i.e. fromBelgium and Sweden (two centres), France, Italy, Spain, Swedenand The Netherlands (each one centre). The coordination of thegroup is in Brussels. The participating centres brought in over15, 000 European workers to test the hypotheses.     

Periodic courses of human 1–34 parathyroid peptide alternating with calcitriol paradoxically reduce bone remodelling in spinal osteoporosis

In an attempt to achieve an anabolic response in both axial and peripheral bone, we treated twelve patients with osteoporosis using human 1-34 parathyroid peptide given discontinuously. The peptide was given as seven daily subcutaneous injections followed by 21 days' treatment with 0.25 mg calcitriol orally. This regime was repeated cyclically for at least sixteen cycles, of which the first four were at a lower dose of hPTH 1-34 than used subsequently. The results of treatment were monitored by kinetic, densitometric, histomorphometric and biochemical studies performed before and during treatment. Two patients developed hPTH 1-34 binding in their plasma during treatment: this was presumed to be due to the development of antibodies. The remainder, instead of increasing their indices of bone turnover as judged by iliac bone histomorphometry, were found to have consistent reductions in trabecular resorption surfaces. The other indices of bone formation and resorption measured showed no change or comparable reductions. The small increases seen in total body calcium were consistent with 'in-filling' of deleted basic multicellular units (BMUs). Because there is no evidence that calcitriol alone causes comparable reductions in activation of bone remodelling in osteoporosis, interruption of treatment with hPTH 1-34 after 7 days may have led to a failure of the activation mechanism to proceed to the resorption stage, with a consequent overall reduction in remodelling activity. This type of treatment regime, with its calcitonin-like effect, might be effective in reducing net bone loss due to imbalance between bone formation and resorption at the BMU level, particularly in patients with increased numbers of BMUs ('high turnover' osteoporosis).(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of a new sonically cleavable and acido-labile handle for solid-phase peptide amide synthesis

A new handle usable for solid-phase peptide amide synthesis was designed. New releasing conditions of the peptide using sonication allowed much shorter reaction times at lower TFA concentrations.     

Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population‐based cohort study

Aim The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population‐based cohort of very preterm infants. Method As part of EPIPAGE, a population‐based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. Results The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2wks; range 24–32wks) and a mean birthweight of 1367g (SD 393g; range 450–2645g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7–10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2wks; range 24–32wks) and a mean birthweight of 1305g (SD 386g; range 500–2480g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03–2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95–3.14) were predictors of the development of CP in very preterm infants. Interpretation Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.     

Immunological aspects of psoriasis. VI. Impairment of isoprenaline and theophylline-induced inhibition of mitogen responsiveness

Pharmacological abnormalities occur in the psoriatic epidermis, and if similar abnormalities occur in the peripheral blood mononuclear cells they could impair the immune responses in psoriasis. In a paired control study, we have tested the capacity of histamine, isoprenaline and theophylline (10^?5 and 10^?7 M) to inhibit the mitogen responsiveness of blood mononuclear cells from normal and psoriatic subjects, using phytohaemagglutinin and concanavalin A. In the normal controls, mitogen responsiveness was inhibited by all three pharmacological agents by about 30 to 50%. In cells from psoriatic patients, the response in the presence of histamine was inhibited (as in the controls), but isoprenaline caused no inhibition, and theophylline paradoxically increased the mitogenic responses. These results suggest there is a defect in the pharmacological response of the blood mononuclear cells in psoriasis.     

INACTIVATION OF CEREBELLAR NITRIC OXIDE SYNTHASE BY ETHANOL IN VITRO

The N-methyl-D-aspartate receptor/nitric oxide synthase (NOS)/guanylatecyclase pathway, which plays a crucial role in synaptic plasticityin the brain, is modulated by ethanol. We studied the effectof ethanol in vitro on NOS in rat cerebellum and showed thatethanol (25–200 mM) inactivated NOS in a dose-dependentmanner. This inactivation was prevented by the biopterin cofactortetrahydrobiopterin (BH⁴) as well as by L-arginine, a NOS substrate,but not by NADPH. These results suggest that ethanol reducesNOS activity by modulating the conformation of the enzyme andthereby its stability, probably by interacting with the bindingsites of BH⁴ and/or of L-arginine. Our data also suggest thatinactivation of NOS may contribute to the decrease in the cGMPlevel, and thus may play a role in the pharmacological actionsof ethanol in vivo.