EFFECTS ON GROWTH HORMONE SECRETION FOLLOWING INTRAVENOUS AND SUBCUTANEOUS INJECTIONS OF GROWTH HORMONE-RELEASING FACTOR (hGRF-44 NH2): COMPARISON OF IMMUNOREACTIVE PLASMA GRF LEVELS

The effects of subcutaneous administration of three doses of human growth hormone-releasing factor (hGRF-44 NH2 or hGRF) at doses of 100, 300 and 600 micrograms were studied in six normal young men. GH responses obtained with 100 and 300 micrograms were negligible. In contrast, the 600 micrograms dose gave a profile of response comparable in timing and magnitude to that obtained with i.v. hGRF at maximal effect doses (20, 80, 100 micrograms). Plasma immunoreactive hGRF levels (IR-hGRF) were compared after s.c. and i.v. hGRF. Mean maximal plasma concentrations were comparable with s.c. 600 micrograms and i.v. 20 micrograms. Peaks occurred earlier with i.v. hGRF (5 min as opposed to 15 min): however, return to undetectable values was obtained between 90 and 120 min after s.c. or i.v. injections. These data suggest a great loss of the peptide between the subcutaneous space and blood, without delayed absorption. High variability in plasma IR-hGRF concentrations between the subjects after the same s.c. doses was observed.     

Thiol groups and reduced acidogenicity of dental plaque in the presence of metal ions in vivo

Metal ions are known to influence the cariogenicity of dental plaque. Inhibition of acid metabolism in plaque may be of importance in this respect. Metal ions inhibit the acidogenicity of dental plaque to a different extent and it has been suggested that an enzyme inhibition based on oxidation of thiol groups may explain this observation. The aim of the present study was to evaluate the significance of oxidation of thiol groups in the inhibition of acid production in plaque by silver, tin and zinc salts. Nine subjects with 3-d sucrose induced plaque received topical applications of the metal ions. Cysteine or gilutathione, which are known to reverse thiol oxidations, were then applied in one side of the mouth. Plaque pH measurements, in the presence of sucrose, were performed prior to and up to 2 h after treatment. The results showed that the acid production inhibited by the metal ions was reactivated by cysteine or glutathione. Iodoacetamide and ρ-chloromercuribenzoate were also shown to inhibit acid formation in dental plaque. The high affinity silver, tin and zinc have for SH groups, the observed inhibitory effect of these metals, the reactivation of the metabolism by monothiols and the fact that organic sulfhydryl reagents inhibit acid formation in plaque indicate that oxidation of thiol groups may be the mechanism by which these metals exert their effect.     

Activation of PAR2 receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint

Background and Purpose

The PAR₂ receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR₂ activation in the rat knee joint.

Experimental Approach

PAR₂ in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR₂ with its activating peptide, 2-furoyl-LIGRLO-NH₂ (1–100 nmol·100 μL⁻¹, via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR₂ activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR₂ activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH₂ or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK₁) receptors in the PAR₂ responses were assessed using the selective antagonists, SB366791 and RP67580 respectively.

Key Results

PAR₂ were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH₂ increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH₂ also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH₂ alone).

Conclusions and Implications

PAR₂ receptors play an acute inflammatory role in the knee joint via TRPV1- and NK₁-dependent mechanisms involving both PAR₂-mediated neuronal sensitization and leukocyte trafficking.     

Coronary fistula from left main stem to main pulmonary artery

We describe a patient with a rare coronary arteriovenous fistula connecting the left main stem to the main pulmonary artery. This rare case was discovered during routine coronary angiography for the evaluation of the patient s coronary heart disease.     

介入治疗激素性股骨头坏死的实验研究

目的：探讨介入治疗激素性股骨头坏死的作用机制。方法：将24只兔子随机分为对照组、模型组、介入组。于介入前后行血管造影检查，并于治疗后8周，分别进行血液流变学、血脂及病理学观察。结果：介入组血管中断现象改善，终末小血管数目增我。全血粘度、血浆粘度，红细胞聚集指数、总胆固醇、甘油三脂，股骨头空骨陷窝率均明显低于模型组（P＜0．05），软骨下区血管数目增多（P＜0．01）。结论：介入、静脉注射治疗股骨头坏死，可以降低血脂，改善血液循环，通过改善股骨头血供，降低骨内压，促进坏死骨修复和新骨再生。     

Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients

OBJECTIVE: Alpha-linolenic acid (ALA) is the natural precursor of the cardioprotective long-chain n-3 fatty acids. Available data indicate a possible beneficial effect of ALA on cardiovascular disease (CVD), but the response of various CVD risk factors to increased ALA intake is not well characterized. The purpose of the present study was to examine the effect of increased ALA intake on blood pressure in man. DESIGN, SETTING, SUBJECTS AND INTERVENTIONS: We used a prospective, two-group, parallel-arm design to examine the effect of a 12-week dietary supplementation with flaxseed oil, rich in ALA (8 g/day), on blood pressure in middle-aged dyslipidaemic men (n=59). The diet of the control group was supplemented with safflower oil, containing the equivalent n-6 fatty acid (11 g/day linoleic acid (LA); n=28). Arterial blood pressure was measured at the beginning and at the end of the dietary intervention period. RESULTS: Supplementation with ALA resulted in significantly lower systolic and diastolic blood pressure levels compared with LA (P=0.016 and P=0.011, respectively, from analysis of variance (ANOVA) for repeated measures). CONCLUSIONS: We observed a hypotensive effect of ALA, which may constitute another mechanism accounting in part for the apparent cardioprotective effect of this n-3 fatty acid.     

DNA Index in childhood acute lymphoblastic leukaemia: a karyotypic method to validate the flow cytometric measurement

The DNA index (DI) is a prognostic factor in childhood acute lymphoblastic leukemia (ALL). The accuracy of DI measurement is important for treatment stratification: hyperdiploidy with DI ≥ 1.16 is predictive of favorable prognosis whereas hypodiploidy is associated with poor prognosis. The aim of this study was to validate the accuracy of the DI measured by flow cytometry (FCM) by comparison with the karyotype. From samples of 112 childhood ALL, we created a formula to calculate a theoretical DNA index (tDI) based on the blast cell karyotype, taking into account the additional or missing chromosome material of the major clone. FCM DI correlated with tDI calculated from karyotype (R = 0.987) and with modal chromosome number (DI = 0.0202 × Modal NB + 0.0675 and R = 0.984). In three cases a hypodiploid blast cell population was detected by FCM, while only the duplicated clone was identified by the karyotype. The strong correlation between tDI and DI validates the accuracy of FCM quantification, which is technically fast on fresh or frozen samples. If the karyotype is essential to analyze chromosomal abnormalities, FCM provides complementary information in aneuploid ALLs, either by confirming the cytogenetic data or by detecting additional clones not identified when only using cytogenetic data.     

Human soluble leptin receptor concentration in healthy offspring of hypertensive parents

Essential hypertension is associated with increased plasma leptin levels and decreased human soluble leptin receptor (hsLR) concentration. The aim of this study was to determine whether the concentration of hsLR differs among offspring of hypertensive compared with nonhypertensive parents. Subjects in the 2 groups were matched for age, sex, and body mass index. Forty-six (24 male, 22 female; mean age, 18+/-3 years; body mass index, 22.4+/-1.4 kg/m2) healthy offspring of hypertensive parents (group A) and 50 (28 male, 22 female; mean age, 18+/-3.2 years; body mass index, 22.6+/-1.7 kg/m2) healthy offspring of healthy parents (group B) were studied. The hsLR concentration (enzyme-linked immunosorbent assay method) and leptin plasma levels (radioimmunoassay method) were determined in the study population. Plasma leptin levels were significantly higher (10+/-5 vs 6+/-3 ng/mL; P<.001), while hsLR concentration was significantly lower (20+/-7 vs 29+/-8 U/mL; P<.001) in group A compared with group B. Our findings suggest that offspring of hypertensive parents have significantly higher plasma leptin levels and significantly lower hsLR concentrations compared with healthy offspring of healthy normotensive parents. Further studies are needed to determine the clinical significance of these observations.     

Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia

Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. For this purpose, we first determined the genomic organization of ITGA6, and placed the gene on chromosome 2q by high resolution radiation hybrid mapping. Heteroduplex analysis of PCR products containing the individual exons of ITGA6, followed by direct nucleotide sequencing, revealed that the proband was homozygous for a G-to-T transversion in the +1 position of intron 12. This mutation, 1856+1G-->T, affects an invariant base of the 5' donor splice site predicting aberrant splicing involving exon 12. The mutation was verified in the proband's DNA by restriction enzyme digestion which also confirmed that the parents were heterozygous carriers of this mutation. Altered expression of alpha6 integrin, which forms a heterodimer with the beta4 subunit at the dermal-epidermal junction, would explain fragility and blistering as a result of minor trauma to the skin.