Lipotoxin F of Pseudomonas aeruginosa is an AlgU-dependent and alginate-independent outer membrane protein involved in resistance to oxidative stress and adhesion to A549 human lung epithelia.

Chronic lung infection with P. aeruginosa and excessive neutrophil-associated inflammation are major causes of morbidity and mortality in patients with cystic fibrosis (CF). Overproduction of an exopolysaccharide known as alginate leads to the formation of mucoid biofilms that are resistant to antibiotics and host defences. Alginate overproduction or mucoidy is controlled by a stress-related ECF sigma factor AlgU/T. Mutation in the anti-sigma factor MucA is a known mechanism for conversion to mucoidy. Recently, we showed that inactivation of a kinase (KinB) in nonmucoid strain PAO1 results in overproduction of alginate. Here, we report the initial characterization of lipotoxin F (LptF, PA3692), an OmpA-like outer membrane protein that exhibited increased expression in the mucoid PAO1kinB mutant. The lipotoxin family of proteins has been previously shown to induce inflammation in lung epithelia, which may play a role in CF disease progression. Expression of LptF was observed to be AlgU-dependent and upregulated in CF isolates. Deletion of lptF from the kinB mutant had no effect on alginate production. Deletion of lptF from PAO1 caused a differential susceptibility to oxidants that can be generated by phagocytes. The lptF and algU mutants were more sensitive to hypochlorite than PAO1. However, the lptF mutant displayed increased resistance to hydrogen peroxide. LptF also contributed to adhesion to A549 human lung epithelial cells. Our data suggest that LptF is an outer membrane protein that may be important for P. aeruginosa survival in harsh environments, including lung colonization in CF.

The influence of the new benzodiazepine derivative BD-1158 on the behaviour of rabbits in spontaneous conditions.

BD-1158 is a new 1,4 benzodiazepine derivative. The purpose of the present experiments was to test the spontaneous behaviour (typical of a rabbit) after administration of BD-1158 and thus to define the activity and side effects of this substance under physiological conditions. The experiments were performed for 3 subsequent days in a group of 10 rabbits. On the first day spontaneous behaviour was tested. On the second day 1 ml of 1% starch solution was administered intraperitoneally. On the third day BD-1158 was administered intraperitoneally at a dose 10 mg/kg diluted in 1% starch solution up to 1 ml, 35-40 minutes before the beginning of the experiment. Six phases of behaviour were estimated. It was concluded that BD-1158 has a strong anxiolytic and sedative effect, decreases the state of animal's attention, water and food uptake.

Changes in rabbits' behaviour under the influence of corticotropin derivative analogue 4-10 in spontaneous conditions.

The influence and the role of corticotrophin analogue 4-10 on the rabbits' behaviour in spontaneous conditions was analysed. The data analysis indicated that analogue 4-10 with modified aminoacid sequence in 8, 9, 10 positions significantly influenced the behavioural changes in the general model of behaviour. The 4-10 corticotrophin derivative caused the suppression of aggression, considerably reduced the tension and orientation-cognition reactions, however, it prolonged comfort and grooming significantly. This may prove the noticeable reaction of analogue 4-10 in modification of behavioural pattern, which was expressed by restraining the reaction of stressogenic character with simultaneous attenuation and prolongation of appetite reactions.

Influence of salmon calcitonin on the analgesic effect of selective kappa-opioid agonist in mice.

In the present study the relationship between calcitonin and kappa-opioid system was analysed. The possibility that salmon calcitonin (S-CT) exerts analgesic activity in mice as well as the influence of salmon calcitonin on the analgesic effect of kappa-opioid agonist, U-50, 488H were examined. The writhing test in mice was used as analgesic test. S-CT given alone intraperitoneally at a high dose produced antinociceptive effect. S-CT given at a subanalgesic dose increased the antinociceptive effect of kappa-opioid agonist, U-50, 488H. The obtained results suggest that the increase in the effectiveness of kappa-opioid receptor agonist may be one of the mechanisms involved in the analgesia induced by salmon calcitonin.

The effect of ascorbic acid supplementation on the blood lead levels of smokers.

BACKGROUND: The study subjects were 75 adult men (20 to 30 years of age), who smoked one pack of cigarettes per day (minimum) and had no clinical signs of ascorbic acid deficiency or lead toxicity. None had a history of industrial exposure to lead, and the blood-lead levels were anticipated to be below 1.45 micromol/L, the minimum blood level associated with toxicity symptoms. METHODS: The men were randomly assigned to three study groups of 25, and each group was provided a four-week supply of one level of daily ascorbic acid supplements (placebo, 200 mg or 1000 mg of ascorbic acid). We measured baseline and weekly serum and urine ascorbic-acid levels as well as blood and urine lead levels. The weekly group means and variations of the measured data were statistically compared by means of ANOVA and Pearson's correlation. RESULTS: The serum ascorbic-acid levels of the groups receiving ascorbic acid increased significantly after one week (p< or =.001). There was no effect of placebo or 200 mg ascorbic-acid supplementation on the blood or urine lead levels. However, there was a 81% decrease in blood-lead levels in the 1000 mg ascorbic acid group after one week of supplementation (p< or =.001). CONCLUSIONS: Daily supplementation with 1000 mg of ascorbic acid results in a significant decrease of blood-lead levels associated with the general population. Ascorbic acid supplementation may provide an economical and convenient method of reducing blood-lead levels, possibly by reducing the intestinal absorption of lead.

Bedtime dosing of glyburide and the treatment of type II diabetes mellitus.

Suppression of nocturnal hepatic glucose production is key in the treatment of noninsulin-dependent diabetes mellitus (NIDDM). In this article, the authors compare the effectiveness of dosing glyburide at bedtime versus in the morning on glycemic control in patients with NIDDM under suboptimal control. In a placebo-controlled, double-blind crossover trial, 32 patients with NIDDM with suboptimal control on chronic glyburide treatment fulfilling entry criteria were randomized to receive one of two regimens: (1) glyburide at bedtime and placebo in morning or (2) placebo at bedtime and glyburide in the morning. After 6 months of a regimen, patients crossed over to the other treatment and completed an additional 6-month period. After baseline assessment, fasting blood sugar, history, physical exam, and compliance assessments were performed monthly. HbA1c was measured bimonthly and Sustacal tolerance tests were performed at the end of each 6-month treatment period. During the initial 6-month comparison fasting, blood sugar concentration decreased 5% in bedtime ingesters and rose 10% in the morning patients. These changes were not statistically significant. HbA1c decreased significantly in the morning group but remained unchanged in the bedtime group. At the end of 12 months, nighttime dosing resulted in better home glucose monitoring values, fasting blood sugar results, and Sustacal tolerance profiles, but the differences were not statistically significant. No hypoglycemia was observed in the monitored data collected. Bedtime dosing of glyburide resulted in measurable improvement in fasting blood sugar and carbohydrate tolerance curves, but not to a degree justifying general recommendation of this technique in patients with NIDDM with secondary failure to oral agents.

Clinical accuracy of capillary blood glucose monitoring in hospitalized patients with diabetes.

This study evaluated the clinical accuracy of capillary blood glucose monitoring (CBGM) performed by nursing personnel on hospitalized patients with diabetes. We compared the results of 80 serum glucose samples obtained in a blinded fashion within 5 minutes of routine capillary glucose measurements performed during the course of clinical care. The CBGM results obtained by a diabetes nurse specialist during endocrine testing procedures were correlated with the serum results. Correlation of CBGM to serum glucose ranged from .74 to .99 depending on the method used. Visual and manual interpretation yielded the lowest correlation and variable accuracy results, per error grid analysis, with 1 in 4 patients having errors of sufficient magnitude that could lead to inappropriate therapy. Monitoring with the AccuChek II blood glucose meter produced the highest correlation and most accurate clinical readings. Bedside blood glucose monitoring of inpatients has a wide range of reliability depending on the method used.

Effect of ascorbic acid supplementation on the sperm quality of smokers.

OBJECTIVE: To determine the effect of ascorbic acid supplementation on the sperm quality of heavy smokers. DESIGN: Microscopic examination of semen for 1 month during supplementation with placebo or ascorbic acid at dose levels of 200 or 1,000 mg/d. SETTING: Department of Obstetrics and Gynecology, The University of Texas Medical Branch. PARTICIPANTS: Seventy-five men (20 to 35 years old) randomly divided into one of three supplementation groups: placebo, 200 mg and 1,000 mg of ascorbic acid. MAIN OUTCOME: Improvement in sperm quality as compared with presupplementation levels and between the three treatment groups. RESULTS: The placebo group showed no improvement in sperm quality. The groups receiving ascorbic acid showed improvement in sperm quality with most improvement in the 1,000-mg group. Pearson's correlation showed statistically significant relationships between the weekly group means of serum and seminal plasma ascorbic acid levels and sperm qualities. CONCLUSIONS: Ascorbic acid supplementation of heavy smokers in excess of 200 mg/d results in improved sperm quality.

Outbreak of adenoviral infections in a long-term paediatric facility, New Jersey, 1986/87.

During an 8-week period in the winter of 1986-87, there were 11 deaths from an adenovirus infection (case fatality rate = 39%, 11/28) in a long-term care paediatric facility in southern New Jersey. Among the 61 resident children, all with severe congenital and/or acquired disabilities, 28 developed a febrile respiratory illness compatible with adenovirus infection [attack rate (AR) = 46%]. Patients with tracheostomies were three times as likely to become ill [relative risk (RR) = 3.2, 95% confidence intervals (CI) = 1.8-5.6]. Twenty-three members of the staff had a similar febrile illness (AR = 22%, 23/106); nurses were more likely to be ill than other staff (RR = 3.0, 95% CI = 1.1-11.4). Adenovirus 7 was isolated from four of the case patients and adenovirus 1 from one. The findings suggest prolonged transmission between patients and nursing staff with lack of cohorting of ill patients probably contributing to the prolongation of the outbreak. This investigation indicates that adenoviral outbreaks, although rare, can have a high mortality in severely disabled children, and that future outbreak investigations should examine the use of vaccines or antiviral agents to reduce mortality and for outbreak control.

Epidemiology of congenital syphilis.

Between 1984 and 1987, the number of reported cases of congenital syphilis in New Jersey tripled. Findings indicate an increase in early syphilis among females of childbearing age living in areas of high syphilis morbidity, reflecting, possibly, lifestyle changes within populations already at risk for the disease. Future studies and interventions are needed.

Human fibroblast collagenase: glycosylation and tissue-specific levels of enzyme synthesis.

Human skin fibroblasts secrete collagenase as two proenzyme forms (57 and 52 kDa). The minor (57-kDa) proenzyme form is the result of a partial posttranslational modification of the major (52-kDa) proenzyme through the addition of N-linked complex oligosaccharides. Human endothelial cells as well as fibroblasts from human colon, cornea, gingiva, and lung also secrete collagenase in two forms indistinguishable from those of the skin fibroblast enzyme. In vitro tissue culture studies have shown that the level of constitutive synthesis of this fibroblast-type interstitial collagenase is tissue specific, varies widely, and correlates with the steady-state level of a single collagenase-specific mRNA of 2.5 kilobases. The tumor promoter, phorbol 12-myristate 13-acetate, apparently blocks the control of collagenase synthesis resulting in a similarly high level of collagenase expression (approximately equal to 3-7 micrograms of collagenase per 10(6) cells per 24 hr) in all examined cells. The constitutive level of synthesis of a 28-kDa collagenase inhibitor does not correlate with that of the enzyme. Phorbol 12-myristate 13-acetate stimulates the production of this inhibitor that in turn modulates the activity of collagenase in the conditioned media. As a result, the apparent activity of the enzyme present in the medium does not accurately reflect the rate of its synthesis and secretion.