Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress,ethanol, indomethacin,and capsaicin neurotoxicity

Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10µg/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500µg/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.     

High Dose Adenosine Stress Echocardiography for Noninvasive Detection of Coronary Artery Disease

Objectives. The aim of this study was to assess the tolerability and incremental diagnostic value of high adenosine doses in stress echocardiography testing in patients with coronary artery disease (CAD).

Background. In comparison with other pharmacologic stress echocardiography tests, standard dose adenosine stress has suboptimal sensitivity for detecting milder forms of CAD.

Methods. Adenosine stress echocardiography was performed in 58 patients using a starting dose of 100 μg/kg body weight per min over 3 min followed by 140 μg/kg per min over 4 min (standard dose). If no new wall motion abnormality appeared, the dose was increased to 200 μg/kg per min over 4 min (high dose). All patients underwent coronary angiography. Significant CAD was defined as ≥50% diameter stenosis in at least one major coronary artery. Thirty-three patients had one-vessel and seven had multivessel CAD. Coronary angiographic findings were normal in 18 patients.

Results. The high adenosine dose caused a slight but significant increase over baseline values in rate-pressure product. Limiting side effects occurred in two patients during the standard dose protocol and in one patient receiving the high dose regimen. The test was stopped in 30 patients after the standard adenosine dose regimen because of a provoked new wall motion abnormality. The sensitivity of adenosine echocardiography with the standard dose was 75% (95% confidence interval [CI] 63% to 87%). After completion of the standard dose protocol, 28 patients continued testing with the high dose adenosine protocol. The overall sensitivity of adenosine echocardiography, calculated as cumulative, increased to 92% (95% CI 84% to 100%) with the high dose (p < 0.05). The specificity of adenosine testing was 100% and 88%, respectively, with the standard and high dose regimen (p = 0.617).

Conclusions. We believe that use of a higher than usual adenosine dose protocol for stress testing may improve the diagnostic value of adenosine echocardiography, mainly by increasing sensitivity in patients with single-vessel disease without deterioration of the safety profile and with only a mild reduction in specificity.

(J Am Coll Cardiol 1996;28:1689–95)>     

Antineutrophil cytoplasmic antibodies (ANCA): diagnostic utility and potential role in the pathogenesis of vasculitis

Antineutrophil cytoplasmic antibodies (ANCA) are a heterogeneous group of circulating antibodies directed toward the cytoplasmic constituents of neutrophils and monocytes. ANCA have been described in various diseases including idiopathic systemic vasculitides, connective tissue diseases, inflammatory bowel diseases, autoimmune liver diseases, infectious diseases, and some drugs. ANCA recognize different target antigens such as proteinase 3 (PR3-ANCA), myeloperoxidase (MPO-ANCA), cathepsin G, lactoferrin, bactericidal/permeability-increasing protein (BPI), and some others. However, only PR3-ANCA and MPO-ANCA are closely associated with systemic vasculitides, in particular Wegener's granulomatosis, microscopic polyangiitis and its renal limited manifestation, and Churg-Strauss syndrome. Both in vitro and in vivo experimental data strongly support a pathogenic role for ANCA in vasculitis and glomerulonephritis.     

Suitability of blood-pressure-to-height ratio as the criterion for high blood pressure in children in an environmental study

Background: Blood-pressure-to-height ratio is considered a simple, accurate, inexpensive and non-age-dependent index for screening high blood pressure in a clinical setting, but its suitability in epidemiological surveys was not taken into consideration. The aim of this study was to test the suitability of blood-pressure-to-height ratio against blood pressure for age percentiles for the identification of high blood pressure in an environmental study.

Methods: The sample consisted of 2195 children, aged 3 to 15 years, whose blood pressure was measured as part of an environmental study in Belgrade, Serbia. High blood pressure was estimated using percentiles (gold standard) and blood-pressure-to-height ratios for systolic and diastolic pressures separately (proposed criterion). The optimal cut-offs of the blood-pressure-to-height ratio (BPHR) were selected based on Youden’s index (sensitivity?+?specificity???1) calculated from the receiver operator characteristic curve analysis.

Results: The proposed criterion identified five times more cases of high blood pressure in the investigated children of all age groups in comparison to the gold standard. The optimal cut-off values were selected based on the sensitivity and specificity values by age groups and gender.

Conclusion: Blood-pressure-to-height ratio can be a reliable criterion for the estimation of high blood pressure in epidemiological studies. This is the first study on the applicability of blood-pressure-to-height ratio in Serbian children, but it may not be easily generalized to other populations due to small sample size across the examined age groups and potential diversities in risk factors for high blood pressure. Applied in epidemiological studies, BPHR would help researchers estimate the role of certain environmental factors on blood pressure in children.     

Amplified-Fragment Length Polymorphism Fingerprinting of Mycoplasma Species

Amplified-fragment length polymorphism (AFLP) is a whole-genome fingerprinting method based on selective amplification of restriction fragments. The potential of the method for the characterization of mycoplasmas was investigated in a total of 50 strains of human and animal origin, including Mycoplasma genitalium (n = 11), Mycoplasma pneumoniae (n = 5), Mycoplasma hominis (n = 5), Mycoplasma hyopneumoniae (n = 9), Myco plasma flocculare (n = 5), Mycoplasma hyosynoviae (n = 10), and Mycoplasma dispar (n = 5). AFLP templates were prepared by the digestion of mycoplasmal DNA with BglII and MfeI restriction endonucleases and subsequent ligation of corresponding site-specific adapters. The amplification of AFLP templates with a single set of nonselective primers resulted in reproducible fingerprints of approximately 60 to 80 fragments in the size range of 50 to 500 bp. The method was able to discriminate the analyzed strains at species and intraspecies levels as well. Each of the tested Mycoplasma species developed a banding pattern entirely different from those obtained from other species under analysis. Subtle intraspecies genomic differences were detected among strains of all of the Mycoplasma species analyzed. The extent of polymorphism varied markedly between the analyzed mycoplasmas, comprising pattern similarity levels from 61.7% detected among M. dispar strains to 95.9% detected among M. genitalium strains. The results of the present study provide evidence of the high discriminatory power of AFLP analysis, suggesting the possible applicability of this method to the molecular characterization of mycoplasmas.