Involvement of IL-16 in the induction of airway hyper-responsiveness and up-regulation of IgE in a murine model of allergic asthma

Experiments were designed to investigate the role of IL-16 in a mouse model of allergic asthma. OVA-sensitized mice were repeatedly exposed to OVA or saline aerosols. Bronchoalveolar lavage fluid (BALF) was collected after the last aerosol, and the presence of IL-16 was evaluated using a migration assay with human lymphocytes. Migration of lymphocytes was significantly increased in the presence of cell-free BALF from OVA-challenged mice compared with BALF from saline-challenged controls. This response was significantly inhibited after addition of antibodies to IL-16, demonstrating the presence of IL-16 in BALF of OVA-challenged animals. Immunohistochemistry was performed and revealed IL-16 immunoreactivity particularly in airway epithelial cells but also in cellular infiltrates in OVA-challenged mice. IL-16 immunoreactivity was absent in nonsensitized animals; however, some reactivity was detected in epithelial cells of sensitized but saline-challenged mice, suggesting that sensitization induced IL-16 expression in airway epithelium. Treatment of mice with antibodies to IL-16 during the challenge period significantly suppressed up-regulation of OVA-specific IgE in OVA-challenged animals. Furthermore, antibodies to IL-16 significantly inhibited the development of airway hyper-responsiveness after repeated OVA inhalations, whereas the number of eosinophils in bronchoalveolar lavage or airway tissue was not affected. In conclusion, IL-16 immunoreactivity is present in the airways after sensitization. After repeated OVA inhalation, IL-16 immunoreactivity is markedly increased and IL-16 is detectable in BALF. Furthermore, IL-16 plays an important role in airway hyper-responsiveness and up-regulation of IgE but is not important for eosinophil accumulation in a mouse model of allergic asthma.     

Effect of nitric oxide synthesis inhibition with nebulized L-NAME on ventilation-perfusion distributions in bronchial asthma

Patients with clinically stable asthma may show ventilation-perfusion (V'A/Q') mismatch. Nitric oxide (NO), a potent endogenous vasodilator, is increased in exhaled air of asthmatics. Such an increased NO production may be detrimental for optimal V'A/Q' balance owing to the potential inhibition of hypoxic pulmonary vasoconstriction. This study was undertaken to investigate the relationship between the concentration of NO in exhaled air and the degree of gas-exchange impairment and to assess the effect of nebulized N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthesis, on gas exchange in patients with asthma. Twelve patients (four females and eight males, aged 31+/-5 yrs) with clinically stable asthma (forced expiratory volume in one second (FEV1) 80+/-5%) not treated with glucocorticoids and increased exhaled NO (58+/-9 parts per billion (ppb)) were studied. Exhaled NO, respiratory system resistance (Rrs), arterial blood gases and V'A/Q' distributions were measured before and 30, 60, 90 and 120 min after placebo or L-NAME (10(-1) M) nebulization; in eight patients pulmonary haemodynamics were also measured. At baseline no relationships between exhaled NO and gas-exchange measurements were shown. Nebulized L-NAME induced a significant decrease in exhaled NO (p< 0.001), which was maximal at 90 min (-55+/-5%). However, after L-NAME no changes in Rrs, arterial oxygen tension, the alveolar-arterial pressure difference in oxygen or V'A/Q' distributions were shown and nebulized L-NAME did not modify pulmonary artery pressure. In conclusion, the degree of gas-exchange impairment in stable asthma is not related to nitric oxide concentration in exhaled air and nitric oxide synthesis inhibition with N(G)-nitro-L-arginine methyl ester does not alter gas exchange or pulmonary haemodynamics, such that ventilation-perfusion disturbances do not appear to be related to an increased synthesis of nitric oxide in the airways.     

A multicenter, randomized, blind comparison of amrinone with milrinone after elective cardiac surgery

The ability of transglutaminase-synthesized 1,3-diaminopropane, spermidine (Spd), spermine (Spm), and monodansylcadaverine gamma-(glutamyl5)derivatives of substance P (SP) to produce bronchoconstriction was investigated. In urethane-anaesthetized guinea pigs, intravenous injections of SP derivatives contracted differently bronchial smooth muscle and caused hypotension. The most effective bronchoconstrictor among SP analogs was the gamma-(glutamyl5)Spd derivative of SP (Spd-SP; EC50 = 5.3 nmol/kg), which was more potent than the native peptide (EC50 = 26.5 nmol/kg). In contrast, the gamma-(glutamyl5)Spm derivative of SP (Spm-SP) was found completely unable to cause bronchoconstriction and was significantly less effective than SP in determining hypotension. The contractile effect of Spd-SP and Spm-SP was investigated in vitro on rat isolated colon, a well-characterized preparation rich in NK2 receptors. In addition, Spd-SP was tested on the endothelium-denuded rabbit pulmonary artery (RPA) and the hamster isolated trachea (HT), both tissue preparations containing only a single functional receptor subtype (NK2A and NK2B, respectively). The results obtained showed that Spd-SP recognizes NK2 receptors occurring on rat isolated colon more effectively (EC50 = 11 nM) than the native peptide (EC50 = 45 nM). Conversely, Spm-SP evokes a contractile response less effective than that elicited by SP (EC50 = 312 nM). Furthermore, Spd-SP (0.1-10 microg kg(-1)) produced a concentration-dependent contraction of both HT and RPA, exhibiting a potency respectively 12 and 30 times higher than SP in contracting HT and RPA. Our results indicate that the introduction of a Spd moiety at the level of glutamine-5 of SP gives rise to an analog that possesses a different capability to recognize NK2 receptors than the parent peptide. Moreover, since Spd-SP seems to contract more effectively RPA than HT, we conclude that it preferentially recognizes the NK2A receptor subtype.     

Cystatin C, and inhibitor of bone resorption produced by osteoblasts

Spermatozoa embedded in the outer perivitelline layer and points of hydrolysis (holes) produced by spermatozoa in the inner perivitelline layer of chicken and turkey eggs were found to be evenly distributed and linearly correlated (r = 0.80 for both species) throughout the layers from most regions of the egg, except from those directly over the germinal disc, in which there were more holes. In turkey eggs there appeared to be relatively fewer perivitelline spermatozoa, since many had degenerated beyond recognition. In eggs from both species, there were approximately 25 times more holes mm-2 in the inner perivitelline layer from over the germinal disc region than that from other regions of the egg. The relationship between these two frequencies could also be described as linear (r = 0.81 for chicken and 0.78 for turkey eggs), although there was some evidence for a saturation effect for holes over the germinal disc. The fertile status of eggs was shown to be a function of all of the above parameters. Eggs from both species had a 50% probability of being fertile when around 3 spermatozoa penetrated the inner perivitelline layer over the germinal disc and showed maximum fertility when more than 6 spermatozoa penetrated this region. Spermatozoa in the outer perivitelline layer and holes in the inner perivitelline layer from regions other than over the germinal disc could also be used to predict fertility, although with less certainty. Since the number of spermatozoa interacting with the egg reflects the numbers of those stored in the uterovaginal sperm storage tubules, the relationships derived in this work should be useful for understanding how fertility in chickens and turkeys is a function of oviducal sperm storage and transport.     

Absence of Epstein-Barr virus (EBV) in a gastrointestinal stromal cell tumour (GIST) in an adult human immunodeficiency virus-seropositive patient with past EBV infection

Gastrointestinal stromal cell tumours (GIST) of the small intestine are rare malignancies. Recently, an association of Epstein-Barr virus (EBV) with malignant stromal cell tumour in young people with AIDS and past EBV infection has been described. We describe a 33-year-old heterosexual male with asymptomatic human immunodeficiency virus (HIV) infection who had had an EBV infection in the past and who presented with an EBV-negative GIST. The association between EBV and malignant stromal cell tumours in young people with AIDS could not be reconfirmed in our adult patient. The relationship between EBV and malignant stromal cell tumours in AIDS patients and the possible pathogenetic role of EBV remains to be established, at least in adults.     

Effects of non-glycated and glycated glucagon-like peptide-1(7-36) amide on glucose metabolism in isolated mouse abdominal muscle

This study investigated the actions of non-glycated and glycated glucagon-like peptide-1(7-36)amide (tGLP-1) on glucose uptake and metabolism in isolated mouse abdominal muscle. Monoglycated tGLP-1 (Mr 3463.8) was prepared under hyperglycemic reducing conditions and purified by HPLC. Non-glycated tGLP-1 (10(-10)-10(-8) mol/l) stimulated both 2-deoxy-D-[1-3H]glucose uptake (1.3-1.5 fold) and 14C-glucose oxidation (1.4-1.7 fold) in muscle compared to controls without tGLP-1. Glycation reduced these stimulatory effects by 27-33% and 25% (at 10(-9) mol/l), respectively. tGLP-1 (10(-10)-10(-8) mol/l) promoted muscle glycogenesis and lactate production, whereas glycated peptide was ineffective below 10(-9) mol/l. This study demonstrates that tGLP-1 has potent glycogenic effects in mouse abdominal muscle in vitro and that glycation impairs its action.     

Enhanced accumulation of ribavirin and its metabolites in liver versus erythrocytes in mice administered with the liver targeted drug

OBJECTIVE: Determine the frequency and relationship between ischemic heart disease (IHD) and serum cholesterol levels (SCL) in non insulin dependent diabetes mellitus (NIDDM) of the primary medical care level. MATERIAL AND METHODS: A total of 411 patients from the first medical care level were studied. The sociodemographic profile, SCL and glycemia were determined and conventional ECG was taken. The ST uneveness, ischemic T or pathological Q waves in two or more tappings was considered as IHD. Patients with history of IHD were not included. RESULTS: The male:female ratio was 1.5:1. Mean SCL was 225 mg/dl (in females 240.8 +/- 56 mg/dl and 220.7 +/- 50.7 in males). In 90 patients we identified IHD (22%), with male predominance (0.85:1, F:M). In the stratified statistical analysis the SCL > or = 200 mg/dl and IHD were significantly associated. The frequency of IHD by SCL levels of 200-239 mg/dl was 24.6% (OR 2.04; CI 95% 1.03-4.07, p = 0.04) and 24.2% (OR 1.99; CI 95% 1.02-3.96, p = 0.04) for SCL of 240-300 mg/dl; in patients with SCL > 300 mg/dl, an increase of IHD to 38.7% was observed (OR 3.95; CI 95% 1.52-10.30, p = 0.002). CONCLUSIONS: The hypercholesterolemia was one of the most important cardiovascular risk factors in NIDDM, in which SCL > or = 200 mg/dl must be considered strongly associated to IHD.     

CT angiography of cerebral venous circulation: anatomical visualization and diagnostic pitfalls in interpretation

PURPOSE: To show the frequency of visualisation of the dural sinuses and cerebral veins with CT-angiography (CTA) with special reference to anatomical variants. METHODS: 34 CTA (1 mm slice thickness, 120 ml nonionic KM, 2 ml/s flow, 40 s prescanning delay) were performed in 30 patients to examine the cerebral venous system. In an anatomic study of cadavers (n = 10) without known disease of the cerebral veins the great sinuses were opened and examined. RESULTS: The superior sagittal, the transverse, the sigmoid and the straight sinus could be evaluated in all cases (100%). The cortical and deep cerebral veins as well as the small sinuses were visualised in 12-97% of the examinations. A sinovenous thrombosis was diagnosed in 4 of the 30 patients. Asymmetric superior sagittal sinus bifurcation (12/30), a hypoplastic sinus transversus (2/30) and a persistent sinus occipitalis (4/30) were found as anatomical variants. In 10 of the 30 patients we discovered 17 dural sinus filling defects produced by large arachnoid granulations. Similar findings could be demonstrated in the pathologico-anatomic examination series. CONCLUSION: CT angiography is suitable for detailed evaluation of the cerebral veins. Anatomic variants, arachnoid granulations, as well as fibrous bands and septa, which may lead to misinterpretation in conventional CT, can be clearly demonstrated. The sensitivity and specificity of CT in diagnosis of sinovenous thrombosis were increased thereby.     

Sterility of anesthetic and resuscitative drug syringes used in the obstetric operating room

Because of the constant threat of emergent cesarean delivery, anesthetic induction and resuscitation drugs are often drawn into syringes and stored in the obstetric operating room (OR). This study investigated the potential for bacterial and fungal contamination of six drugs (thiopental, succinylcholine, ephedrine, atropine, lidocaine, and oxytocin) often prepared in the obstetric OR. A total of 756 drug syringes were prepared and stored in the obstetric OR for 8 days using normal clinical practices. Starting on Day 0, and subsequently on Days 4 and 8 of the experiment, 42 syringes of each drug were randomly selected from the pool, filtered through a 0.45-microm porosity sterile cellulose filter, and cultured on 5% sheep blood agar. Of the 756 syringes tested, none grew organisms of any type, which indicates a probability of drug sterility of > or = 0.9961 (95% confidence interval [CI]). The data from the cultures performed on syringes on Day 0 indicate a probability of initial contamination of < or = 0.018 (95% CI). This study demonstrates a high probability of sterility in drugs drawn into sterile syringes and stored at room temperature in an OR environment for up to 8 days. Implications: Drug syringes stored in emergency operating rooms are discarded after 24 h because of possible contamination. We searched for microorganisms in drug syringes stored in the operating room for up to 8 days. No microbes were detected using standard sterility testing techniques. Adopting longer storage periods could result in significant cost savings.