The tracheal nonadrenergic noncholinergic inhibitory system during antigen challenge

This study was undertaken to test the hypothesis that malfunction of the nonadrenergic noncholinergic inhibitory system (NANCIS) induces hyperreactive airways. Antigen sensitized guinea pigs were divided into four groups: (1) antigen challenge (n = 6), (2) 2 min oxyhemoglobin (HbO2) + antigen challenge (n = 5), (3) 27 min HbO2 + antigen challenge (n = 4), and (4) 2 min HbO2 + transmural stimulation (TS) + antigen challenge (n = 6). These animals were sensitized with ovalbumin 10 days before the study. In addition, 12 normal control animals without antigen sensitization were used for comparison. Under artificial ventilation, the anesthetized-paralyzed animals were hourly injected with atropine (0.2 mg/kg) and propranolol (1 mg/kg). Cervical segment of the trachea was converted to a closed tracheal pouch filled with Krebs solution containing also atropine (1 microM) and propranolol (3.5 microM). A change in the pouch pressure (Pp) reflected NANCIS TS- or antigen (5 micrograms) challenge-induced relaxation and/or constriction. HbO2 was used to inhibit NANCIS transmitter. There was no significant difference between normal and sensitized animals in the NANCIS TS-induced relaxation. Antigen challenge resulted in biphasic alteration in Pp, an initial increase and then a decrease after about 7 min. HbO2 pretreatment alone did not potentiate antigen-induced increase in Pp. HbO2 + TS, however, significantly abolished the late relaxation phase after antigen challenge.     

Anal Canal Cancer

PURPOSE: This study was designed to obtain an updated population-based perspective on anal canal cancer incidence rates, demographics, and outcomes using a nationwide database. Eight-five percent of all carcinomas of the anus are anal canal cancers, and previous studies suggest that incidence rates may be rising. Although the most successful treatment for anal canal cancer has been chemoradiation, little information at the population-level exists regarding demographics, treatment, and survival. METHODS: All patients diagnosed with anal canal cancer from 1973 to 1998 in the Surveillance Epidemiology and End Results cancer registry were analyzed. Data regarding demographics, cancer characteristics, treatment, and survival were assessed. Univariate and multivariate survival analyses were performed. RESULTS: A total of 4,841 patients were studied (mean age was 61 years; 62 percent female). Female patients were significantly older than male patients (65 vs. 58 years; P < 0.0001). There was a yearly increase in incidence of anal canal cancers (from 1973–1998). Disease prevalence by stage was localized (53 percent), regional (38 percent), and distant (9 percent). Racial/stage differences were seen, because black patients had less localized disease than white patients (46 vs. 53 percent; P < 0.01). Overall five-year survival for the entire cohort was 53 percent, and cancer-specific survival was 84 percent. Survival improved per decade (based on year of diagnosis). Significant survival differences in race were noted, but were less when the receipt of treatment was considered. CONCLUSION: Although most anal canal cancer reviews are single institutional series, this study was performed with population-based data. The incidence of anal canal cancer is increasing, and overall survival rates are improving. Important disparities in care were identified, which need to be addressed.     

Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients

BACKGROUND: Reactive oxygen species may contribute to the pathogenesis of asthma. Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE: To investigate the association of the manganese-containing form of SOD (MnSOD) gene at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS: The association study was conducted in a case-control design in asthma patients (n=251) and healthy controls (n=316) by genotyping. The functional significance was assessed by determining erythrocyte SOD and catalase activity. RESULTS: The Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were not different between patients and controls, while the C allele of catalase gene at C-262T was found to be significantly different between patients and controls (P=0.033). The less frequent variant of catalase gene (-262T) was found to be protective from the development of asthma in a Hong Kong Chinese non-smoking population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had elevated erythrocyte SOD and catalase activities in comparison with healthy controls (P<0.01). However, their activities were not associated with different genotypes within healthy controls or asthma patients. CONCLUSION: This is the first report showing that SOD and catalase functional activities are not associated with their respective genetic polymorphisms but related to the presence of asthma in a Hong Kong Chinese population.     

Haemorrhagic fever with renal syndrome: Clinical aspects

Based on clinical and pathological features a typical case of haemorrhagic fever with renal syndrome passes through five phases: (1) febrile phase, (2) hypotensive phase, (3) oliguric phase, (4) diuretic phase and (5) convalescent phase. The major manifestations are fever, pain in the back and abdomen, flushed face, prostration, proteinuria, purpura and haemorrhage and acute renal failure. Selective right auricular haemorrhage, marked congestion and haemorrhage in the renal medulla and necrosis of the anterior lobe of the pituitary gland are the three prominent pathological findings. The clinical severity depends upon the causative agents, namely Hantaan virus, Seoul virus and the European form in that order. Specific serological diagnosis of haemorrhagic fever with renal syndrome is made by demonstrating a rise in titre of specific immunofluorescent antibody against Hantaan and related viruses. The management is supportive, based on an understanding of the pathophysiology of the disease.     

Evaluation of leukocyte arylsulphatase a, serum interleukin-6 and urinary heparan sulphate following tamoxifen therapy in breast cancer.

Leukocyte arylsulphatase A (AS-A) was shown to be significantly high in newly-diagnosed breast cancer patients. Previous reports imply a connection between serum interleukin-6 (IL-6) and breast cancer, possibly through a modulation of enzymes involved in estrogen synthesis. Abnormal distribution of heparan sulphate proteoglycans (HSPGs) in malignant breast epithelial cells suggests that they play a key role in the regulation of cell growth. Estradiol is believed to be effective in modulating glycosaminoglycans (GAGs) and their depolymerizing enzymes. Therefore, in this study, attempts were made to evaluate the activity of leukocyte arylsulphatase A, serum interleukin-6, urinary GAGs and heparan sulphate (HS) in response to tamoxifen (TAM) therapy in mastectomised breast cancer patients. Thirty-four patients (aged 30-82 years) were administered TAM (20 mg twice daily). Blood and urine samples of each patient were collected three times (at the beginning, and in third and sixth month of TAM therapy), and biochemical parameters were measured. There was no difference between baseline leukocyte AS-A activity and that measured after three months. At the end of six months, enzyme activity was significantly higher than the former values (p=0.022), but within the reference intervals reported in the literature. Although this increase might imply a normalization, the duration of TAM therapy is not long enough to make a decision about either regression or aggravation of the disease. TAM did not have any effect on serum IL-6, urinary HS and GAG levels which may be due to insensitivity of these variables to TAM during the short period of therapy. Both urinary GAG and HS levels measured at sixth month exhibited a positive correlation with the baseline level of leukocyte AS-A (p=0.005 and 0.009, respectively), suggesting that positive responses to the drug might be seen in patients with low AS-A activity.     

Transdermal permeation-enhancing activities of some inorganic anions

Effects of sodium salts of various monovalent inorganic anions on transdermal permeation of salicylic acid were investigated. In in-vitro experiment using a Franz-type diffusion cell and excised mouse skin, the permeation-enhancing activities of the sodium salts of inorganic anions were roughly proportional to lyotropic Hofmeister swelling abilities of the anions; F^?<SO₄ ^2?<Cl^? <ClO₄ ^?<NO₃ <SCN^? <Br <I^?, i.e. l, Br and SCN increased the flux of drugs through the mouse skin, while F^?, SO₄ ^2?, Cl^?, ClO₄ ^? and NO₃ ^? decreased or did not affect the flux. In invivo experiment using the rabbit as the test animal, the plasma concentration of salicylic acid of the rabbit to which 10%-salicylic acid ointment containing 5%-Nal or NaBr was applied was significantly higher than that of the rabbit to which the ointment without the electrolytes was applied. The amounts of sterol leached out of stratum corneum sheet when the sheet was immersed in aqueous solutions of Nal, NaBr, or NaSCN were much more than that of stratum corneum immersed in aqueous solutions of the other inorganic anions. The FTIR/ATR spectroscopy showed that the peaks at 2853 cm^?1 and 2924 cm^?1 in the IR absorption spectrum of the stratum corneum sheet of the mouse were shifted to higher frequencies by the anions which enhanced the transdermal drug permeation, while not shifted by the anions which did not have any permeation-enhancing activities or have permeation-reducing activities. These results suggest that sodium salts of some anions such as iodide, bromide and thiocyanate enhance transdermal permeation of salicylic acid through swelling and perturbation of the skin structure by these anions.