Low-dose sodium nitroprusside reduces pulmonary reperfusion injury

BACKGROUND: Reperfusion injury is a significant cause of early allograft dysfunction after lung transplantation. We hypothesized that direct pulmonary arterial infusion of an intravascular nitric oxide donor, sodium nitroprusside (SNP), would ameliorate pulmonary reperfusion injury more effectively than inhaled nitric oxide without causing profound systemic hypotension. METHODS: Using an isolated, ventilated, whole-blood-perfused rabbit lung model, we studied the effects of both inhaled and intravascular nitric oxide during lung reperfusion. Group I (control) lungs (New Zealand White rabbits, 3 to 3.5 kg) were harvested en bloc, flushed with Euro-Collins solution, and then stored inflated for 18 hours at 4 degrees C. Lungs were then reperfused with whole blood and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 micrograms.kg-1.min-1, respectively, whereas group V was ventilated with 60% oxygen and nitric oxide at 80 ppm during reperfusion. RESULTS: Pulmonary arterial infusions of SNP even at 0.2 microgram.kg-1.min-1 (group II) showed significant improvements in pulmonary artery pressure (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421 dynes.s/cm-5; p < 0.05) when compared with control (group I) lungs after 30 minutes of reperfusion. Infusions of SNP at 1.0 microgram.kg-1.min-1 (group III) showed additional significant improvements in dynamic airway compliance (1.98 +/- 0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05), venous-arterial oxygenation gradient (116.00 +/- 24.4 versus 34.43 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry ratio (6.9 +/- 0.9 versus 9.1 +/- 2.2; p < 0.05) when compared with control (group I) lungs. Lungs that received inhaled nitric oxide at 80 ppm (group V) were significantly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05) than control (group I) lungs. CONCLUSIONS: Pulmonary arterial infusion of low-dose SNP during lung reperfusion significantly improves pulmonary hemodynamics, oxygenation, compliance, and edema formation. These effects were achieved at doses of SNP that did not cause profound systemic hypotension. Direct intravascular infusion of SNP via pulmonary arterial catheters could potentially abate reperfusion injury immediately after allograft implantation.     

The effect of brief illumination on intracellular free calcium concentration in cells with 5-aminolevulinic acid-induced protoporphyrin IX synthesis

The effect of illumination on intracellular free calcium concentration, [Ca2+]i, was studied in a cell line (WiDr cells) derived from a primary adenocarcinoma of the rectosigmoid colon. In these cells the biosynthesis of protoporphyrin IX was stimulated by 5-aminolevulinic acid to reach levels of 600-700 pmol of protoporphyrin IX per mg cell protein. A brief (1-min) exposure of the cells to light (70% of light energy at 340-380 nm) resulted in an increase in [Ca2+]i. This increase was not reversible over a period of at least 20 min following illumination. Elevation of [Ca2+]i most probably represented an influx of calcium ions from the medium to the cell, since it was completely abolished in the presence of extracellular EGTA. The increased [Ca2+]i did not reflect general membrane damage, as determined by trypan blue staining as well as measurement of the intercalation of ethidium bromide into cellular DNA, and neither did the sustained elevation of [Ca2+]i lead to any substantial loss of clonogenicity following illumination of protoporphyrin-containing cells. Together these results indicate that an increased [Ca2+]i level is not per se a cause of cell death during photodynamic therapy.     

Antimicrobial potentials of some plant species of the Bignoniaceae family

The methanol extracts of the leaves and stem bark of four Bignoniaceae plants Jacaranda mimosifolia D. Dol., Tecoma stans Linn., Tabebuia rosea (Bertol) D.C., and Crescentia cujete Linn. were studied for their antimicrobial activity using a wide range of Gram-positive and Gram-negative bacteria and fungi. Extracts of both the leaves and stem bark of majority of plant species studied showed variable but remarkable broad spectrum antimicrobial activity. However, methanol extracts of Tecoma stans leaves was found to be effective against only Candida albicans at the concentrations employed. It was observed that the extracts of stem bark generally showed better antimicrobial activity than those of the leaves and some organisms were selectively more sensitive to the extracts than others. Preliminary phytochemical screening of these plants revealed the presence of tannins, flavonoids, alkaloids, quinones and traces of saponins. The antimicrobial activity observed are discussed in relation to the chemical constituents reportedly isolated from these plants and their traditional uses.     

Serious infections due to Pseudomonas aeruginosa

Infections due to Ps. aeruginosa are a problem in the tropics as in other parts of the world. Over a four year period, 15 patients attending University College Hospital, Ibadan, were proved to have septicaemia due to this organism and 13 patients died rapidly as a direct result of the infection. The two patients who survived the acute episode had received immediate treatment with at least one antibiotic active against Ps. aeruginosa: a third patient, who received immediate appropriate antibiotic therapy, was already suffering from aplastic anaemia and died rapidly despite treatment. The remaining patients received inappropriate antibiotic therapy because pseudomonas infection was not suspected at the time the diagnosis of septicaemia was made. Patients most at risk appear to be the very young and those with pre-existing malignant or other conditions affecting the defence mechanisms of the body: it is suggested that routine initial management of such patients should include a blood culture, followed by immediate treatment with an antibiotic combination that includes at least one agent likely to be active against Ps. aeruginosa. The development of medical services can lead to the introduction of ophthalmic or other operations on tissues that are highly susceptible to infection before facilities are provided for the maintenance of a pathogen-free environment. Following an outbreak of eye infection after cataract extractions, carried out in an old and unsatisfactory theatre, wide-spread room contamination was demonstrated with the same strains of Ps. aeruginosa that had been responsible for the clinical infections. Chemical disinfection of the theatre floor failed to eliminate the organisms, although other experiments suggested that the drying effect of air-conditioning would be successful in this respect. The wisdom of introducing such operations before the provision of adequate facilities is seriously questioned.     

Sonographic and histomorphologic parallels in various histologic variants of chronic myeloid leukemia

Histomorphometric findings at the study of marrow puncture specimens were compared to sonographic picture of the liver and spleen in 20 myeloid leukemia chronic. Histomorphometric and sonographic changes observed showed parallel pathological processes in the hemopoietic micro-surroundings and in the liver, spleen. Sonography proved able to considerably broaden diagnostic armory of the physician, to prognosticate leukemia outcomes, thus suggesting a differential approach to the disease treatment.     

N-glycosylation of recombinant human interferon-gamma produced in different animal expression systems

Recombinant human interferon-gamma (IFN-gamma) was expressed in Chinese hamster ovary cells, baculovirus-infected Sf9 insect cells and the mammary gland of transgenic mice. The N-linked carbohydrate populations associated with both Asn25 and Asn97 glycosylation sites were characterized by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) in combination with exoglycosidase array sequencing. A site-specific analysis of dual (2N) and single (1N) site-occupancy variants of IFN-gamma derived from Chinese hamster ovary cells showed that N-glycans were predominantly of the complex bi- and triantennary type. Although Asn25-linked glycans were substituted with a core fucose residue, Asn97 N-glycans were predominantly non-fucosylated, and truncated complex and high-mannose oligosaccharide chains were also evident. Transgenic mouse derived IFN-gamma exhibited considerable site-specific variation in N-glycan structures. Asn25-linked carbohydrates were of the complex, core fucosylated type, Asn97-linked carbohydrates were mainly of the oligomannose type, with smaller proportions of hybrid and complex N-glycans. Carbohydrates associated with both glycosylation sites of IFN-gamma from Sf9 insect cells were mainly tri-mannosyl core structures, with fucosylation confined to the Asn25 site. These data demonstrate the profound influence of host cell type and protein structure on the N-glycosylation of recombinant proteins.     

Lipidemic effect of methanol

The effect of methanol on some of the lipid components in serum was studied in rats. Methanol was administered by stomach tube in doses of 2 and 6 ml/kg b.wt daily for 21 and 6 days, respectively. Methanol was found to accumulate lipids; thus, cholesterol, phospholipids and triglycerides increased significantly. Concurrently, modification of the lipoid content of organs has been considered. It was concluded that methanol and not only formate, is toxic to rats, inspite of the alleged difference in routes of its metabolism in primates and rodents.     

The correlation of the vasopressin- and oxytocin-producing activities of different nuclei in the hypothalamo-hypophyseal neurosecretory system]

Radioiodine long has proven to be a safe and effective treatment for thyroid disease. Nonetheless, persisting concerns regarding radiogenic stochastic risks (e.g., carcinogenesis) to patients, their families, and the general public have led regulators to establish criteria for release of 131I-containing patients from medical confinement, with limits ranging from as low as 2 mCi in some parts of Europe to as high as 30 mCi in the United States. To optimize clinical efficacy and cost-effectiveness of 131I therapy, such regulations should be based on logical dosimetric considerations. The thyroidal absorbed dose, proportional to maximum uptake and effective half-life and inversely proportional to mass, is typically approximately 1,500 rad/mCi of 131I administered to a euthyroid adult (based on a thyroid maximum uptake of 25%, effective half-life equivalent to the physical half-life of 131I (8.04 days), and mass of 20 g). As thyroid uptake increases from 0% to 100%, extrathyroidal absorbed doses range from a minimum of 0.15 to 0.5 rad/mCi for breast and gonads to a maximum of 1.5 to 2 rad/mCi for stomach and salivary glands; the absorbed doses of the urinary bladder wall, in contrast, decrease with increasing thyroid uptake, from 2 to 0.6 rad/mCi. In hyperthyroid patients (approximately 15%) with a small iodine pool (so-called small patients), the short effective half-life of radioiodine in the thyroid and high serum concentrations of long-lived protein-bound 131I result in a standard 7,000-rad absorbed dose for treatment of Graves' disease requiring an administered activity of 28 mCi of 131I and yielding a prohibitively high blood absorbed dose of 150 rad. Importantly, once the fetal thyroid begins to function and accumulate radioiodine at a gestational age of 10-12 weeks, fetal thyroid absorbed doses as large as 5,000 rad/mCi of 131I administered to the mother can result. Thus, pregnancy is an absolute contraindication to administration of 131I because of the risk of radiogenic cretinism. Based on actual measurements of thyroid activity and of external absorbed dose, the total thyroid and mean extrathyroidal absorbed doses to adult family members from immediately released 131I-treated patients are approximately 0.01 and approximately 0.02 rad/mCi administered, respectively, yielding an effective dose of approximately 0.02 rem/mCi. A maximum permissible effective dose of 0.5 rem for adults therefore is consistent with a release criterion of 30 mCi of retained 131I. Lower-activity release criteria therefore may be unnecessarily restrictive.