Effects of TAK-427 on acute nasal symptoms and nasal obstruction in guinea pig model of experimental allergic rhinitis

TAK-427 (2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate) is a novel anti-allergic agent that has both histamine H1-receptor antagonist and anti-inflammatory activities. In this study, we evaluated the efficacy of TAK-427 on acute nasal responses and nasal obstruction using various guinea pig models of allergic rhinitis. TAK-427 inhibited the histamine-induced nasal reactions with an ID50 value of 0.633 mg/kg, p.o. TAK-427 (0.1-10 mg/kg, p.o.) and most histamine H1-receptor antagonists tested inhibited the increase in intranasal pressure, nasal hypersecretion, sneezing and nasal itching caused by a single antigen challenge in sensitized guinea pigs. In addition, TAK-427 (0.3, 30 mg/kg, p.o.) significantly inhibited the development of nasal obstruction when sensitized guinea pigs were repeatedly challenged via inhalation with Japanese cedar pollen, whereas the histamine H1-receptor antagonist, azelastine (1 mg/kg, p.o.), and ketotifen (1 mg/kg, p.o.) were without effect. These results suggest that TAK-427 might not only suppress acute nasal symptoms but also ameliorate nasal obstruction via the effects other than those as a histamine H1-receptor antagonist.     

Screening for mutations of the androgen receptor gene in patients with isolated cryptorchidism

OBJECTIVE: To evaluate the occurrence of mutations of androgen receptor (AR) gene in patients with isolated cryptorchidism. DESIGN: Controlled clinical study. SETTING: Yamagata University Hospital, Yamagata and Tokyo Electric Power Company Hospital, Tokyo, Japan. PATIENT(S): Patients with isolated cryptorchidism (n = 48) and a control group of men with normal phenotype (n = 20). INTERVENTION(S): Blood (lymphocyte DNA). MAIN OUTCOME MEASURE(S): Screening of the AR gene in exons 1-8 using single-strand conformational polymorphism analysis. RESULT(S): No abnormal band patterns were detected in patients with cryptorchidism or in control subjects within the eight exons of the AR gene. CONCLUSION(S): AR gene alterations appear to be an unlikely cause of isolated cryptorchidism.     

Influence of age and disease severity on high resolution CT lung densitometry in asthma

BACKGROUND: Low attenuation areas (LAA) on computed tomographic (CT) scans have been shown to represent emphysematous changes in patients with chronic obstructive pulmonary disease (COPD). However, the significance of LAA is still controversial in patients with asthma. This study was undertaken to assess the usefulness of lung CT densitometry in the detection of airspace enlargement in association with asthma severity. METHODS: Forty five asthmatic subjects and 15 non-smoking controls were studied to determine the influence of age, pulmonary function, and asthma severity on mean lung density (MLD) and the relative area of the lung showing attenuation values less than -950 HU (RA(950)) on high resolution CT (HRCT) scans. RESULTS: In asthmatic patients both MLD and RA(950) correlated with parameters of airflow limitation (%FEV(1), FEV(1)/FVC, %FEF(25-75)) and lung volume (%TLC, %FRC, %RV), but not with lung transfer factor (%TLCO, %TLCO/VA). The results of HRCT lung densitometry also correlated with patient age and severity of asthma. CONCLUSIONS: Decreased CT lung density in non-smoking asthmatics is related to airflow limitation, hyperinflation and aging, but not with lung transfer factor.     

The complementary role of beta-catenin in diagnosing various subtypes of renal cell carcinomas and its up-regulation in conventional renal cell carcinomas with high nuclear grades

beta-catenin is a kind of cytoplasmic protein involved in cell adhesion and signal transduction. This study investigated its expression in various subtypes of renal cell carcinomas (RCCs) using an immunohistochemical staining method. beta-catenin expression was assessed from staining frequency and staining score. Staining score was performed by evaluating both staining percentage and intensity. All subtypes of RCCs reacted positively with beta-catenin. However, the positive frequency and staining score in papillary and chromophobe RCCs were significantly higher than those in conventional RCCs (p < 0.05). In addition, in conventional RCCs, the positive frequency and staining score of beta-catenin showed a significant difference between nuclear grades I/II and grade III (p < 0.05). Therefore, it may indicate that beta-catenin can serve as a complementary tool to distinguish conventional RCCs from chromophobe RCCs. In conventional RCCs with low nuclear grades, beta-catenin expression is generally down-regulated, while it appears to be preserved in those with high nuclear grades.     

Compliance With the North American Guidelines for Children's Agricultural Tasks (NAGCAT) Work Practice Recommendations for Youth Working With Large Animals

ABSTRACT

The North American Guidelines for Children's Agricultural Tasks (NAGCAT) were developed to reduce the risk of childhood agricultural injury. The purpose of this study was to evaluate compliance with NAGCAT-recommended work practices (WPs) when youth work with large animals. On a daily basis, over a period of 10 weeks, youth self-reported the number of minutes they worked with a large animal and whether they followed the associated NAGCAT WP guidelines. Statistical analyses were conducted to compare boys to girls and to consider the effect of factors such as youth age, farm residence status, and selected parental characteristics. A high proportion of youth exhibited relatively low compliance for most of the five WPs evaluated. Respirators were rarely worn, but checking for people and obstacles in the area while working with large animals was commonly reported. In general, boys, especially the older boys, exhibited higher compliance than did girls. The results of our study demonstrate, in general, that youth are not following recommended NAGCAT WPs when working with large animals, identifying an area in agricultural safety and health requiring focused attention.     

Depletion of hepatic coenzyme A derivatives is one of the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat

When 400 mg/rat/day of secondary autoxidation products of linoleic acid was orally administered 3 times to rats, they died at 30-40 h after the third dose. To search the markers of the toxicity of secondary products in vivo, the rats were killed at 24h after the third dose, and conditions of their digestive tracts and liver were analyzed. In the stomach, macroscopically, inflation, retention of undigested food, and edema were seen. Slight congestions were detected in the small intestines. It was considered that these injuries led to reduction in food consumption and then depression of the growth, but did not lead to the death of the animals. The lipid peroxide levels in the liver and the activities of its detoxifying enzymes were increased as compared to those in the control groups. The hepatic lipid contents and unsaturated fatty acid compositions were also not changed. The endogenous lipid peroxidation, therefore, did not give the rats a severe stress. The activities of hepatic acetyl-CoA carboxylase and carnitine palmitoyltransferase were 20 and 35% lower than those of control, respectively. The levels of CoASH, acetyl-CoA, and long-chain acyl-CoA were 1/9, 1/2, and 1/4 of those in control, respectively. Thus, one of the markers of the toxicity of secondary products was the depletion of hepatic CoA derivatives. In rat, bio-energy was reduced by the decrease in the intestinal absorption of nutrients, and the depletion of hepatic CoA derivatives also failed to supply energy with beta-oxidation.     

CT demonstration of prominent right hilar soft tissue collections

Three cases of normal soft tissue collections of the right hilum which could be confused with thrombus of the right pulmonary artery or adenopathy are demonstrated. These abnormalities are due to normal accumulations of hilar fat and lymph nodes. Their typical appearance allows easy recognition.