Activity of renin-angiotensin-aldosterone system (RAAS) and vasopressin level in patients with primary pulmonary hypertension

AIM: Assessment of RAAS and vasopressin in patients with primary pulmonary hypertension (PPH). MATERIALS AND METHODS: Activity of plasma renin (APR), angiotensin-converting enzyme (ACE), plasma levels of angiotensin II (AII) and vasopressin (VP), serum concentration of aldosteron (AS) were measured by radioimmunoassay and enzyme immunoassay in 21 PPH patients with circulatory failure (age 34.7 +/- 2.1 years), 11 patients with NYHA functional class II-III, 10 with class IV, and 10 control subjects (age 29.8 +/- 1.5 years). RESULTS: Compared to controls, 21 PPH patients had elevated RAAS parameters: APR up to 3.52 ng/ml/h (p < 0.05), activity of ACE up to 43.13 units, AII level up to 33.93 ng/ml (p < 0.01), AS up to 468.86 ng/ml (p < 0.01), VP up to 5.26 ng/ml (p < 0.001). Circulatory failure progression resulted in activation of all the RAAS components. This and VP activation was the greatest in PPH patients with ACE > 5 ng/ml/h. PPH patients with mean pressure in the pulmonary artery higher than 60 mm Hg demonstrated higher ARP, AS, VP, AII, ACE than those who had this pressure under 60 mm Hg. CONCLUSION: PPH patients display a noticeable activation of RAAS and VP. This activation seems to be secondary as the changes increase with elevation of the pressure in the pulmonary artery and aggravation of circulatory insufficiency. Plasma renin activity determines the degree of RAAS activation as a whole. The discovered activation of RAAS in PPH gives grounds for doubts in the validity of using ACE inhibitors in the treatment of PPH.     

The comparative amino acid sequences, substrate specificities and gene or cDNA nucleotide sequences of some prokaryote and eukaryote amidinotransferases: implications for evolution

The amino acid sequences of the amidinotransferases and the nucleotide sequences of their genes or cDNA from four Streptomyces species (seven genes) and from the kidneys of rat, pig, human and human pancreas were compared. The overall amino acid and nucleotide sequences of the prokaryotes and eukaryotes were very similar and further, three regions were identified that were highly identical. Evidence is presented that there is virtually zero chance that the overall and high identity regions of the amino acid sequence similarities and the overall nucleotide sequence similarities between Streptomyces and mammals represent random match. Both rat and lamprey amidinotransferases were able to use inosamine phosphate, the amidine group acceptor of Streptomyces. We have concluded that the structure and function of the amidinotransferases and their genes has been highly conserved through evolution from prokaryotes to eukaryotes. The evolution has occurred with: (1) a high degree of retention of nucleotide and amino acid sequences; (2) a high degree of retention of the primitive Streptomyces guanine + cytosine (G + C) third codon position composition in certain high identity regions of the eukaryote cDNA; (3) a decrease in the specificities for the amidine group acceptors; and (4) most of the mutations silent in the regions suggested to code for active sites in the enzymes.     

Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments

OBJECTIVE: To evaluate an experimental heroin maintenance programme. Design: Randomised trial. SETTING: Outpatient clinic in Geneva, Switzerland. SUBJECTS: Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments. INTERVENTION: Patients in the experimental programme (n=27) received intravenous heroin and other health and psychosocial services. Control patients (n=24) received any other conventional drug treatment (usually methadone maintenance). Main outcome measures: Self reported drug use, health status (SF-36), and social functioning. RESULTS: 25 experimental patients completed 6 months in the programme, receiving a median of 480 mg of heroin daily. One experimental subject and 10 control subjects still used street heroin daily at follow up (difference 44%; 95% confidence interval 16% to 71%). Health status scores that improved significantly more in experimental subjects were mental health (0.58 SD; 0.07 to 1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences. There were no benefits in terms of work, housing situation, somatic health status, and use of other drugs. Unexpectedly, only nine (38%) control subjects entered the heroin maintenance programme at follow up. CONCLUSIONS: A heroin maintenance programme is a feasible and clinically effective treatment for heroin users who fail in conventional drug treatment programmes. Even in this population, however, another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids.     

Prevalence and demographic determinants of metronidazole resistance by Helicobacter pylori in a large cosmopolitan cohort of Australian dyspeptic patients

1. Heterozygous naked neck birds were raised under natural spring (average 21.2 degrees C) and summer temperatures (average 27.1 degrees C) to investigate the influence of dietary energy on broiler performance, carcase yield and nutrient composition of breast meat. 2. Birds were fed on a low energy diet of 12.12 MJ ME/kg, a medium energy diet of 12.96 MJ ME/kg and a high energy diet of 13.79 MJ ME/kg with 2 protein concentrations per energy treatment, 230 and 200 g/kg, from 0 to 3 and 3 to 7 weeks of age, respectively. 3. Summer rearing resulted in a decrease in body weight, body weight gain, carcase weight and carcase part yields of birds. 4. Increasing dietary energy from 12.12 to 13.79 MJ ME/kg increased body weight at 3 and 7 weeks, body weight gains from 0 to 3 and 3 to 7 weeks, carcase weights and relative abdominal fat weights of birds in a linear manner. There was no effect of dietary energy on the nutrient composition of breast meat. 5. It was concluded that there was no differences in dietary energy requirements of heterozygous naked neck birds when grown under natural optimum (21.2 degrees C) and summer temperatures (27.1 degrees C).     

The effect of oxidative stress on structural transitions of human erythrocyte ghost membranes

The influenza virus hemagglutinin (HA) contains three highly conserved cysteine residues at positions 551, 559, and 562 close to the carboxyl-terminus of the HA2 subunit which serve as palmitylation sites. Wild-type HA of influenza virus A/FPV/Rostock/34 (H7N1) and HA permutated by exchange of the acylated cysteine to serine residues were expressed in CV-1 cells by a SV40 vector system. Since density of immunostained HA on the cell surface measured by flow cytometric analysis did not differ between wild-type and acylation mutants, it was possible to compare acylation mutants and wild-type HA for their capacity to induce membrane fusion at low pH. The following observations were made: (1) lateral diffusion of a lipid-like fluorophore (R-18) from the erythrocyte membrane to the plasma membrane of cells expressing HA on the surface occurred equally well with mutants and wild type. (2) Diffusion of a low-molecular-weight fluorescent water-soluble probe (calcein) from erythrocytes into the cytoplasm of HA-expressing cells was not altered either. (3) However, depending on the position and the number of the deleted acylation sites, the mutants showed a reduced ability to induce syncytia. The data indicate that deacylation of the cytoplasmic tail has no measurable effect on the capacity of HA to induce membrane fusion and pore formation but that it suppresses syncytia formation.     

Determination of fibrin and fibrinogen split products by their anticoagulant activity

A new diagnostic method to determine fibrinogen and fibrin splitting products is based on the fact that high-molecular fragments acting as specific inhibitors of fibrin self-assembly compose these products. Fibrinogen and fibrin splitting products are detected and determined quantitatively by prolongation of coagulation time in the test with the standard monomeric fibrin. The number of units of anticoagulating activity in the studied urine are the results of the determinations. Sensitivity of the method if necessary may be increased by adding of a certain amount of the fibrinogen and fibrin splitting products to the test that makes a favourable background for the action of the products. The method is rather sensitive, reliable and simple. It may be used in ordinary clinical laboratories. The method proved to be quite satisfactory when testing renal diseases at the clinic. It is of great significance for early detection of the transplanted kidney rejection. The new method is compared with the known immunological method which consist in determination of the inhibitory effect of the fibrinogen and fibrin splitting products on agglutination of erythrocytes of specific antibodies; the erythrocytes being subjected to "tanning" and "loading" with fibrinogen. A satisfactory correlation is found between the results of two methods.     

Effect of prostaglandin F2alpha on the lysosomal membranes of eye tissues

It was demonstrated that both in vitro and in intravenous injection of prostaglandin F2alpha there occurred labilization of the membranes of sclera and ciliary body lysosomes, in difference from the cornea in rabbits. Glycosidase activity appeared in the vitreous body under the effect of prostaglandin, which was absent under normal conditions.     

Human gamma-interferon expression in the mammary gland of transgenic mice

Transgenic mice carrying a hybrid gene consisting of ovine beta-lactoglobulin gene sequences and human gamma-interferon (hIFN-g) cDNA were produced. hIFN-g expression in the mammary gland of two lactating transgenic founder females was found. The concentration of active hIFN-g in the milk was estimated as being ca. 1800 IU/ml. The hIFN-g ability to express in the mammary gland was found in the progeny of transgenic founder male.     

Use of the method of mixed substrates to study the specificity of tRNA methylases

The absence of summation of the rate of methylation of positionally analogous cytidine residues in tRNA1Val, tRNAPhe, and tRNAMet in the case of simultaneous presence of two substrates in the incubation mixture was demonstrated by the method of mixed substrates. The same result was also obtained in the methylation of A19 (counting from the 3' end of the molecule) in tRNA1Val, tRNAPhe, tRNAfMet, tRNASer, and tRNAGlu individually and in the case of their mixing in pairs. These data are evidence that positionally analogous nucleotides in different RNAs are attacked by the same enzyme. Yeast tRNASer, already possessing a methyl group at the cytidine residue studied, proved to be an effective inhibitor of methylase, forming m5C with valine and phenylalanine tRNAs. The results obtained are evidence that differences in the primary and secondary structures at the site of methylation are not the deciding factors in the interaction of tRNA with methylases.