Influence of the menstrual cycle on skin-prick test reactions to histamine, morphine and allergen

The purpose of this study was to examine the possible influence of the phases of the menstrual cycle on dermal reactivity to skin-prick testing. We studied 15 atopic, menstruating women with seasonal rhinoconjunctivitis and/or asthma, with known sensitivity to olive and parietaria (mean age 25.2 years) and 15 non-atomic, healthy, female controls (mean age 24.7 years). Skin-prick tests with histamine, morphine, and in the atopic group with parietaria/and/or olive, were repeated three times during the same menstrual cycle, corresponding to bleeding (day 1–4), midcycle (day 12–16) and the late progesterone phase (day 24–28). None of the patients had received oral antihistamines or exogenous hormones for at least 1 month prior to testing. Results indicate a significant increase in weal-and-flare size to histamine, morphine, and parietaria on days 12–16 of the cycle, corresponding to ovulation and peak oestrogen levels. This was observed in both atopic and non-atopic women. Differences in skin reactivity to histamine and morphine between the groups were not significant. Therefore, in women, the phase of the menstrual cycle is another factor that may influence skin-test results.     

Synthesis of the very acid-sensitive Fmoc-Cys(Mmt)-OH and its application in solid-phase peptide synthesis

S-4-methoxytrityl cysteine was synthesized and converted into the corresponding Fmoc-Cys(Mmt)-OH by its reaction with Fmoc-OSu. As compared to the corresponding Fmoc-Cys(Trt)-OH, the S-Mmt-function was found to be considerably more acid labile. Quantitative S-Mmt-removal occurs selectively in the presence of groups of the tert butyl type and S-Trt by treatment with 0.5–1.0% TFA. The new derivative was successfully utilized in the SPPS of Tyr¹-somatostatin on 2-chlorotrityl resin. In this synthesis groups of the Trt-type were exclusively used for amino acid side-chain protection. Quantitative cleavage from the resin and complete deprotection was performed by treatment with 3% TFA in DCM–TES (95:5) for 30 min at RT. We observed no reduction of tryptophan under these conditions. © Munksgaard 1996.     

Visualization of Mitral Valve Tunnel Aneurysm by Transesophageal Echocardiography

We report the echocardiographic findings in a patient with a mitral valve aneurysm, probably occurring as a complication of aortic valve endocarditis. Transesophageal echocardiography showed a tunnel-shaped aneurysm of the atrial side of the anterior mitral leaflet, expanding in systole and collapsing in diastole. Transesophageal echocardiography is a useful diagnostic tool for the evaluation of mitral valve pathology.     

Modulators of length of gestation: A study in Greece

In order to ascertain correlates of gestational age and predictorsof prematurity, all the mothers delivered in 1993 at the maternityclinic of the First University Department of Obstetrics andGynaecology and at one division of a private maternity hospitalin Athens, Greece, were interviewed. From a total of 3,770 deliveries,those involving multiple pregnancies or Caesarean deliverieswere excluded, as were pregnancies with an apparent durationof less than 150 or more than 300 days. The analysis was eventuallybased on 2,538 singleton deliveries. The duration of gestationwas modelled as an outcome variable through multiple regression.The following factors were found to be significantly (p<0.05)related to the duration of gestation: maternal education, +0.8day per 3 schooling years; family integrity, single comparedto currently married mother, –3.7 days; parity, muttiparous(4+ births) compared to primiparae, +2.8 days; age at menarche,+1.8 days per 2 years; maternal age, +3.9 days for younger than20 years and –1.7 days for older than 30 years in comparisonto women 20–29 years old; maternal weight before pregnancy,+0.4 day per 5 kg; coffee drinking, +0.7 day per cup per day;tobacco smoking, –1.8 days per 0.5 pack per day. Bleedingduring any trimester of pregnancy and maternal diabetes weresignificantly associated with shorter duration of gestationby 6.7 and 8.2 days respectively. The constellation of riskfactors for a pre-term delivery in Greece appears similar tothat in other populations. However, a positive association betweencoffee drinking and duration of pregnancy has not always beendemonstrated in other studies and the longer duration of pregnancyamong very young women represents an unusual finding. At therange of variation under investigation the individual factorsare not powerful predictors but their combination could identifywomen at high risk for prematurity.     

Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: Interaction with low dose acetylsalicylic acid

1Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases. 2We investigated the effects of captopril (2×25 mg day⁻¹), or ASA (1×100 mg day⁻¹), or the combination of both drugs for 7 days, on blood pressure, prostanoid and NO formation rates in a double-blind, double dummy, randomized crossover study in 13 healthy female subjects. The urinary metabolites of thromboxane A₂ (2,3-dinor-TXB₂) and prostacyclin (2,3-dinor-6-keto-PGF_1α), and PGE₂ were measured by gas chromatography/tandem mass spectrometry in urine on days 1, 6 and 7 of each medication. NO formation was assessed using urinary NO3− and cyclic GMP as indicators. 3Urinary 2,3-dinor-6-keto-PGF_1α excretion was not significantly changed by either captopril, ASA, or their combination. Urinary 2,3-dinor-TXB₂ excretion was inhibited by >80% by ASA alone or in combination with captopril (each P<0.05), but was not affected by captopril alone. Urinary PGE₂ excretion was not significantly changed by either of the treatments. Urinary NO3− and cyclic GMP excretion rates were not significantly changed by captopril, ASA, or their combination. 4Blood pressure was slightly reduced by captopril. ASA had no effect on blood pressure when given alone, nor did it modulate the effect of captopril on blood pressure during co-administration. Angiotensin II/angiotensin I ratio (index of ACE activity) was significantly decreased by captopril alone or in combination with ASA, but was unaffected by ASA alone. 5Captopril does not stimulate prostacyclin formation in healthy human subjects in a dose sufficient to substantially inhibit ACE activity. Co-administration of ASA significantly inhibits 2,3-dinor-TXB₂ excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects.     

Beneficial effect of atorvastatin on erythropoietin responsiveness in maintenance haemodialysis patients

Aim: To evaluate the effect of atorvastatin on erythropoietin responsiveness and whether this effect is mediated by C‐reactive protein (CRP) reduction in prevalent dyslipidemic, haemodialysis patients. Methods: We studied prospectively 33 stable, iron‐repleted haemodialysis patients with low‐density lipoprotein cholesterol (LDL) ≥2.58 mmol/L, who received 20 mg atorvastatin aiming to achieve the target of LDL <2.58 mmol/L, over a period of 9 months. Twenty‐five patients completed the study, 15 men, with mean age 66.1 ± 8.2 years. The duration of haemodialysis was 56.6 ± 63.1 months and 5/25 patients were diabetics. Total serum cholesterol, triglycerides, high‐density lipoprotein cholesterol, LDL, haemoglobin, albumin, intact parathyroid hormone, serum iron, ferritin, total iron binding capacity, CRP and weekly dose of erythropoietin/body weight/haemoglobin were analysed. Results: Twenty of the 25 patients (80%) achieved the goal of LDL <2.58 mmol/L. There was a significant decrease in total cholesterol (5.77 ± 0.88 to 4.16 ± 0.96 mmol/L, P < 0.001) and LDL (3.59 ± 0.77 to 1.94 ± 0.77 mmol/L, P < 0.001). Haemoglobin increased from 121 ± 11 to 126 ± 7 g/L (P < 0.05), while weekly dose of erythropoietin/body weight/haemoglobin decreased significantly from 8.34 ± 3.70 to 7.87 ± 3.11 IU/kg per haemoglobin (P < 0.05). CRP decreased not significantly from 7.0 ± 6.1 to 4.5 ± 2.2 mg/L. Conclusion: Dyslipidemia of haemodialysis patients was treated safely and effectively with atorvastatin, but a fifth of the patients failed to achieve the therapeutic target. Statin therapy resulted in a significant increase of haemoglobin levels and improvement of erythropoietin responsiveness without a significant reduction in CRP levels, suggesting that the beneficial effect of statins on erythropoietin responsiveness may be driven by a mechanism other than CRP reduction.     

2-Chlorotrityl chloride resin

The esterification of 2-chlorotrityl chloride resin with Fmoc-amino acids in the presence of DIEA is studied under various conditions. High esterification yields are obtained using 0.6 equiv. Fmoc-amino acid/mmol resin in DCM or DCE, in 25 min, at room temperature. The reaction proceeds without by product formation even in the case of Fmoc-Asn and Fmoc-Gln. The quantitative and easy cleavage of amino acids and peptides from 2-chlorotrityl resin, by using AcOH/TFE/DCM mixtures, is accomplished within 15-60 min at room temperature, while t-butyl type protecting groups remain unaffected. Under these exceptionally mild conditions 2-chlorotrityl cations generated during the cleavage of amino acids and peptides from resin do not attack the nucleophilic side chains of Trp. Met, and Tyr.     

CGMP Levels Following ANF Challenge are Markers of Subsequent Successful Reversion of Lone Atrial Fibrillation to Sinus Rhythm

The aim of the present study was to assess whether cGMP release to ANP stimulation can be a biochemical marker of subsequent successful electrical cardioversion of lone atrial fibrillation to sinus rhythm. For this purpose, we studied 13 patients with chronic, lone atrial fibrillation of less than one year's duration who presented to our laboratory for electrical therapy of their arrhythmia. Prior to electrical cardioversion, peripheral venous cGMP levels were assessed at baseline and following an tntravenous challenge of 50 Ug human ANP. Venous blood samples for cGMP assessment were taken a) at baseline, b) 5 and 10 mins after the end of ANP infusion. ANOVA of repeated measures was used for statistical analysis. Eight of the study patients were successfully cardioverted to sinus rhythm, while the remaining 5 were not. Although no difference was noted between the two groups regarding the mean time of arrhythmia duration as well as left atrial and ventricular dimensions, ANP stimulation provoked significantly greater cGMP release in patients whose arrhythmia reverted to sinus rhythm, when compared with that of patients whose arrhythmia persisted (p<0.001). Therefore, cGMP levels following ANP challenge might discriminate between patients with chronic AF who are going to be successfully cardioverted and those who are not. These findings imply that the underlying atrial disease might be different in extent/nature between patients with lone AF responsive to cardioversion and those with resistant arrhythmia.     

Methylation in positions 1 and 7 of angiotensin II A structure-activity relationship study

Six analogues of angiotensin II (Ang) were synthesized with modifications in positions 1 and 7. The study was undertaken in order to learn more about the influence of alkylations in positions 1 and 7 and their interdependence. Previous studies have shown that x,x-dimethylation of Gly (aminoisobutyric acid, Aib) in position 1 produces quite potent analogues, as does N-methylation of Gly (sarcosine). Combination of both C^x- and N^x-methylations to N-Me-Aib¹, however, did not produce an affinity increase. Decyclisation of the Pro⁷-residue produced moderately active analogues with position 7 N-methylation and inactive analogues if the N-alkylation was suppressed. In order to investigate a possible stereochemical interdependence of positions 1 and 7, a group of peptides with combinations of position 1 and 7 alkylations were investigated. The following analogues were prepared: [Sar¹, Aib⁷]Ang, [Sar¹,Aib⁷,Leu⁸]Ang, [Aib^1,7]Ang, [Aib^1,7, Leu⁸]Ang, [N-Me-Aib¹,Aib⁷]Ang, [N-Me-Aib¹,Aib⁷,Leu⁸]Ang. They were synthesized by classical solid phase synthesis using the BOC-TFA-HF scheme. The biological properties of these peptides were assessed on the rabbit aorta preparation and their binding potencies were measured on bovine adrenal membranes. Both on agonistic and antagonistic [Leu⁸]Ang analogues single Aib substitutions in position 1 or 7 induced affinity reduction in both bioassays. Simultaneous Aib modifications in positions 1 and 7 induced more important affinity loss in a synergic manner in both bioassays and as well for agonists and antagonists. The N-Me-Aib¹ modifications induce similar affinity loss with or without concomitant Aib⁷ modification. Agonistic (Phe⁸) analogues containing Aib in position 7 all have reduced intrinsic activity, indicating for the first time an influence of this position on the activation mechanism of the Ang receptor of the Type AT₁. © Munksgaard 1994.     

Dentinogenic potential of the dental pulp: facts and hypotheses

The aim of the present article is to discuss observations and hypotheses from different experimental approaches on the biological mechanisms underlying initiation of tertiary dentin formation and therapeutic control of pulp–dentinal regeneration. The specific dentinogenic potential of dental pulp cells in up‐regulating the biosynthetic activity of primary odontoblasts (reactionary dentinogenesis) and differentiation into odontoblast‐like cells (reparative dentinogenesis) is described. The role of biologically active matrices and molecules as signaling factors in the expression of the dentinogenic potential of dental pulp cells, in numerous ex vivo and in vivo models, is reviewed. Data are focused on the mechanisms by which the signaling molecules, in the presence of the appropriate pulp microenvironment and specific mechanical support, can induce competent pulpal cells in the acquisition of odontoblast‐like cell phenotype and reparative dentin formation. The ability of tissue engineering to stimulate reconstruction of the amputated pulp–dentin complex offers exciting opportunities for the future. Advances in molecular biology and bioengineering research might thus be integrated into the clinical problems of endodontology.
Received 13 February 2009; accepted 2 September 2009.