Preliminary Phase I Study of Human Leukocyte Interferon: Side Effects of the Interferon

Human leukocyte interferon was administered systematically to13 Japanese patients and its side effects were evaluated. Systemicadministration of interferon caused a temporary febrile responsein most of the patients. Intravenous injection caused a moresevere but shorter response than intramuscular injection. Thelong-term administration of interferon caused an increase inneutrophils for one or a few months in six patients. No otherside effects were found in any of the patients. Because theside effects may be due to the impurity of the interferon preparations,more highly purified interferon should be used from now on.     

Comparison of intravenous digital subtraction cineangiocardiography with conventional contrast ventriculography for the determination of the left ventricular volume at rest and during exercise

Left ventricular volumes were determined by means of digitalsubtraction cineangiocardiography (DSA) which was performedin the right anterior oblique projection after contrast agentinjection into the superior vena cava. Monoplane end-diastolic(EDV), end-systolic volumes (ESV), and ejection fraction (EF)were calculated using the ‘area–length’ methodand were compared with the same parameters obtained by conventionalleft ventricular cineangiocardiography. A first group of 20patients was studied at rest and a second group of 10 patientsduring bicycle exercise at a work load of 64 watts during 2min, by DSA and conventional cineangiocardiography. Three differentsubtraction modes were evaluated: (1) mask mode subtraction(MMS), (2) time interval difference (TID) method and (3) a combinationof MMS and TID called MMS+TID method. With the MMS method goodcorrelations were obtained for EDV, ESV and EF at rest (r>0.91)and during exercise (r>0.91). The TID method showed onlymoderate correlations for patients at rest (r>0.86) and duringexercise (r>0.79). Similar results as with MMS were achievedby the combined method (MMS+TID) at rest (r>0.91) and duringexercise (r>0.91). Interobserver variability indicated ahigh reproducibility for all methods except for TID during exercise.Itis concluded that DSA is an accurate technique for left ventricularvolume determination not only at rest but also during exercise.The best results are obtained with MMS or MMS+TID methods, whileleft ventricular contour detection is easier and more convenientwith MMS+TID.     

Azosemide-Induced Fetal Wavy Ribs and Their Disappearance after Birth in Rats

ABSTRACT Azosemide produced bent long bones such as wavy ribs in rat fetuses, but these abnormalities could not be found in the adult offspring. In the present study, the morphological sequence from appearance to disappearance of wavy ribs was examined in cartilage-bone double stained specimens of fetuses and pups from mothers treated with azosemide on day 16 of gestation. The first detected change of the skeletal abnormalities was inhibition of bone deposition in the ossification centers of fetuses on day 17 of gestation. A bend first appeared on day 18 of gestation, and consisted of cartilage and portion stained neither alcian blue nor alizarin red S. Ossification began at this stage. From day 19 of gestation onward, ossification progressed toward the ends of the cartilage model including the bent region. The bend disappeared in most pups as bone in the bent region grew on days 10–14 postpartum. The present findings imply that the bend may be caused by difference in growth between cartilaginous and unstained portions, and a surface remodeling of bones may straighten the bend in the subsequent bone growth.     

Ability of preschool children to use dry powder inhalers as evaluated by In-Check Meter

BACKGROUND: Although current guidelines recommend the pressurized metered-dose inhaler with a spacer for preschool children with asthma, dry powder inhalers (DPI) may be a valuable treatment alternative. METHODS: To evaluate the ability of preschool children to inhale through DPI, peak inspiratory flow rates (PIFR) of 57 healthy children aged 3-6 years were measured with In-Check Meter after practising with an instructor. Two different calibrated resistances were attached to the Meter to mimic the internal resistance of each inhaler; Diskus and Turbuhaler. RESULTS: The ability of children to generate adequate inspiratory flow increased with age. The percentages of the 3-, 4-, 5-, and 6-year-old children who were able to inhale reliably through the devices were 30% (3/10), 79.0% (15/19), 100% (16/16), and 100% (12/12), respectively. In these children, 100%, 93.3%, 100%, and 100% achieved an adequate PIFR for the Diskus (30 L/min). In contrast, 66.7%, 66.7%, 62.5%, and 91.7% generated an adequate PIFR for the Turbuhaler (60 L/min). CONCLUSIONS: The In-Check Meter is a useful device to assess the ability of preschool children to generate adequate PIFR for each inhaler. Most children aged > or =5 years could use DPI.     

Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin‐induced mouse model of asthma

Background and objective: In asthma, reduced histone deacetylase activity and enhanced histone acetyltransferase activity in the lungs have been reported. However, the precise function of Sirtuin 1 (Sirt1), a class III histone deacetylase, and the effect of the Sirt1 activator SRT1720 on allergic inflammation have not been fully elucidated. Methods: The effect of SRT1720, a synthetic activator of Sirt1, in an ovalbumin (OVA)‐induced asthma mouse model was investigated. The effect of SRT1720 and resveratrol on OVA stimulation in splenocytes from OVA‐sensitized and challenged mice was also examined. Results: In OVA‐sensitized and challenged mice (OVA mice) compared with saline‐sensitized and challenged mice (control mice), Sirt1 messenger RNA expression in the lungs was decreased (P = 0.02), while cellular infiltration, airway eosinophilia and bronchoalveolar lavage (BAL) fluid levels of interleukin (IL)‐4, IL‐5 and IL‐13 were increased (P < 0.01). In OVA mice, SRT1720 treatment decreased total and eosinophil cell counts and IL‐5 and IL‐13 levels in the BAL fluid compared with the vehicle treatment (P < 0.05). In OVA mice, SRT1720 treatment also decreased inflammatory cell lung infiltrates histologically (P = 0.002). Both SRT1720 and resveratrol suppressed OVA‐induced cell proliferation and IL‐6 (P < 0.05) and tumour necrosis factor‐α (TNF‐α) (P < 0.05) production in splenocytes (P < 0.01). Conclusions: The Sirt1 activator SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA‐induced mouse model of asthma. SRT1720 and resveratrol suppressed OVA‐induced splenocyte proliferation and TNF‐α and IL‐6 production. Sirt1 activators might have beneficial effects in asthmatics by suppressing inflammation.