Renal Disposition of Recombinant Human Interleukin-11 in the Isolated Perfused Rat Kidney

Purpose. To clarify the mechanism of the renal clearance of recombinant human interleukin-11 (rhIL-11), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney. Methods. The disposition characteristics of ¹¹¹In-labeled rhIL-11 were analyzed using a single-pass indicator dilution technique and statistical moment analysis in the perfused rat kidney under filtering and nonfiltering conditions. Results. Steady-state distribution volume (V _d ) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 g/kidney was between 0.35 and 0.40 ml/g kidney. However, V _d at the highest dose decreased to a value almost identical to that of bovine serum albumin, suggesting that there is a reversible and saturable interaction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its urinary excretion was highly restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but still significant renal uptake. Taken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the capillary side. These processes were not saturable within the tested dose range. These characteristics of rhIL-11 are likely based on non-specific electrostatic interaction with the tissues due to its cationic charge in the cytokine. Conclusions. The renal disposition processes of rhIL-11 were clarified at organ level in a quantitative manner. These findings agree well with previous observations in an in vivo disposition study in mice.     

Growth-suppressive activities of serine protease inhibitors, FOY-305, ONO-3403 and FO-349 toward human carcinoma cells

FOY-305 is a synthetic serine protease inhibitor and ONO-3403 and FO-349 are its derivatives. The effects of these compounds on the proliferation of several human carcinoma cell lines were investigated in vitro by MTT colorimetric assay. ONO-3403 showed the most potent growth-inhibitory activity among these protease inhibitors. The half maximum inhibition concentrations of ONO-3403 toward BxPC-3 pancreatic carcinoma, T24 bladder carcinoma and A431 epidermoid carcinoma cells were 20-30 mu g/ml whereas those toward pancreatic carcinomas, PANC-1 and Mia PaCa-2, were 60-80 mu g/ml. Since FOY-305 has been shown to be effective in chemotherapy for human oral cancer, ONO-3403 is expected to be a more effective anticancer drug.     

Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer.

PURPOSE: The aim of this study was to determine whether collagen XVIII expression is correlated with circulating serum endostatin and whether this has any prognostic value in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Serum endostatin levels were measured quantitatively by a competitive enzyme immunoassay, and collagen XVIII expression in tumor tissue was investigated with an immunohistochemical method in a series of 94 patients who underwent surgery for NSCLC. RESULTS: Sixty cases (63.8%) had positive immunohistochemical staining with anticollagen XVIII polyclonal antibodies, including strongly positive staining in 11 (11.7%) cases. The mean (+/- SD) serum endostatin level was 41.6 +/- 34.4 ng/ml in the patient group and 16.3 +/- 10.3 ng/ml in the control group (P < 0.0001). The 11 cases who were strongly collagen XVIII-positive had significantly higher serum endostatin levels than the cases who were negative or weakly positive (P = 0.0297). The 5-year survival rates of negative, weakly positive, and strongly positive patients were 77.8%, 56.9%, and 43.8%, respectively. The cases with strongly positive collagen XVIII expression had a significantly poorer outcome than cases with negative expression (P = 0.0027). A multivariate analysis with Cox proportional hazards model for disease-specific survival revealed that expression of collagen XVIII (strongly positive versus negative; weakly positive versus negative), tumor classification, and regional lymph node classification were independent prognostic factors. CONCLUSIONS: Our results suggest that expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in NSCLC and correlates with elevated levels of circulating serum endostatin.     

Fixed eruption due to quinine in tonic water: A case report with high‐performance liquid chromatography and ultraviolet A analyses

Fixed drug eruption is a common cutaneous adverse reaction in young patients with a characteristic clinical appearance. However, the diagnosis and identification of the substance may be difficult if food or food additives provoke the fixed eruption. A 26‐year‐old man had a history of two episodes of cutaneous erythema with residual pigmentation. Close examination of the history including his diet in addition to an oral challenge test and patch testing led to the diagnosis of fixed eruption secondary to quinine in tonic water. We examined for the presence of quinine in commercially available brands of tonic water using ultraviolet A and irradiation and high‐performance liquid chromatography. Both Schweppes and CANADA DRY brands of tonic water emitted fluorescent light upon ultraviolet A irradiation, and contained quinine at concentrations of 67.9 and 61.3 mg/L, respectively. Quinine contained in some tonic waters may trigger fixed eruption.     

Matrix Metalloproteinases in the Pathogenesis of Asthma and COPD

While asthma is an inflammatory disorder of the airways involving mediators released from mast cells and eosinophils, inflammation alone is insufficient to explain the chronic nature of the disease. Recent progress in the understanding of disease pathogenesis has revealed that airway remodeling, which is at least in part due to an excess of extracellular matrix (ECM) deposition in the airway wall, plays a significant role in airflow obstruction. Matrix metalloproteinases (MMPs) have been suggested to be the major proteolytic enzymes to induce airway remodeling in asthma and COPD. It has been widely accepted that different inflammatory processes are involved in asthma and COPD with different inflammatory cells, mediators, and responses to treatments. Despite these different processes, airflow obstruction and airway remodeling characterize these two diseases. MMP-2 and -9 have been reported to be involved in the pathogenesis of airway remodeling in both diseases and MMP-12, in addition to these MMPs, in the pathogenesis of COPD. In this review, we discuss the current views on the role of MMPs in the pathogenesis of bronchial asthma and COPD. Anti-MMP therapy could theoretically be useful to prevent airway remodeling in asthma and COPD. However, to date no clinical data are available regarding the efficacy of anti-MMP therapies in the treatment of patients with asthma and COPD.     

Trends in Asthma Mortality in Japan

Asthma mortality has been increasing in many developed countries in recent years, so we have described the epidemiological features of asthma in Japan. Data on all certified asthma deaths from 1950 to 1997 were obtained from The National Vital Statistics, published annually by the Ministry of Health and Welfare. Trends in crude and age-adjusted asthma mortality rates, as well as age-specific mortality rates, were analyzed. Age and birth cohort effects on mortality rates were also examined using multiplicative models. Between 1950 and 1980, crude asthma mortality rates steadily decreased in both sexes and began to level off thereafter. Age-adjusted mortality rates have also decreased since 1950, and showed a persistent downward trend in both sexes even in recent years. Asthma mortality rates were higher in males than in females during the entire study period. When analysis was restricted to those aged 5 to 34 years, an upward trend since 1980 was observed. The multiplicative model showed a rapidly decreasing cohort effect on mortality among those born after 1860. However, the slope increased in the cohorts born after 1950 in both sexes. The age effect increased linearly with advancing age after 50 years in both sexes. Overall asthma mortality rates have been decreasing during the past five decades in Japan, but the mortality rate has increased among the 5-34-year-old age group since 1980. The high fatality rate stemming from the overuse of beta 2-agonists may account for the mortality increase.     

Impact of air-conditioner outlet layout on the upward airflow induced by forced air warming in operating rooms

BackgroundPreviously, we found that an upward air current in the head area, induced by forced air warming (FAW), was completely counteracted by downward laminar airflow. However, this study did not include any consideration of the air-conditioner outlet layout (ACOL); hence, its impact remains unclear.MethodsThis study was performed in 2 operating rooms (ORs)—ISO classes 5 and 6, which are denoted as OR-5 and OR-6, respectively. Both ORs have distinct ACOLs. The cleanliness, or the number or ratio of shifting artificial particles was evaluated.ResultsDuring the first 5 minutes after particles generation, significantly more particles shifted into the surgical field in OR-5 when compared to OR-6 (13,587 [4,341-15,913] and 106 [41-338] particles/cubic foot, P < .0001). Notably, FAW did not increase the number of shifting particles in OR-6. The laminar airflow system fully counteracted the upward airflow caused by FAW in OR-6, where the ACOL covered the operating bed. However, this did not occur in OR-5, where the ACOL did not fully cover the operating bed.ConclusionsRegardless of cleanliness ability of OR, an ACOL that fully covers the operating bed can prevent upward airflow in the head area and reduce the number of artificial particles shifting into the surgical field, which are typically caused by FAW.