Rabbits are frequently used as laboratory animals or kept as domestic pets. Rabbit serum albumin and a 17‐kDa protein referred to as Ory c 1 have previously been reported as allergens. Several other allergenic proteins have been recognized by crossed immuno‐electrophoresis but have not been characterized. The aim of this study was to characterize the allergenic proteins present in rabbit saliva, urine and fur on the basis of molecular size and, where possible, to determine their amino acid sequences. Extracts from the male New Zealand white rabbit were used for developing specific direct RAST and RAST inhibition assays. Proteins in the extracts were separated by SDS‐PAGE and the individual allergens identified by immunoblotting with serum from rabbit‐allergic individuals. The N‐termini of four allergens were sequenced. Saliva was the most potent extract. In total, 26 protein bands were recognized as allergens in the three extracts: 12 in saliva, seven in urine and seven in fur. Their molecular weights ranged from an 8‐kDa species in saliva to an 80‐kDa protein in urine. The N terminal sequences of an 18 kDa and a 21‐kDa species in saliva, were identified as lipocalins with sequence similarity to a recently described odourant binding protein. This is the first evidence that allergens from the rabbit are members of the lipocalin superfamily of proteins, suggesting that similar mechanisms may be involved in eliciting the allergic response to rabbits. The 18 kDa allergen from saliva may be the previously named rabbit allergen, Ory c 1.
Abstract The authors undertook this study to assess levels of cadmium exposure in the general population. Samples of lung, liver, and kidney were obtained from 61 cadavers (43 males, 18 females; 2–89 yr of age, mean age = 38.5 yr) who died from accidental causes and who were subject to postmortem examinations at the John Tonge Centre for Forensic Sciences, Queensland Health Scientific Services, Brisbane, Australia, in 1997 and 1998. Samples of bladder urine were also obtained from 22 cadavers. Tissue and urine samples were analyzed for cadmium, zinc, and copper with inductively coupled plasm (ICP) mass spectrometry. The overall mean values for cadmium in the lung, liver, and kidney cortex samples were 0.13, 0.95, and 15.45 μg/gm wet tissue weight. The average renal cadmium level in subjects with high lung-cadmium levels (n = 13) was 6 μg/gm wet tissue weight higher than that of similarly aged subjects who had medium lung-cadmium levels (n = 30). In females, the average level of cadmium in the liver was 74% greater than in males, and the average liver cadmium in females with high lung-cadmium levels was 100% higher than in males in the same age range who had the same high lung-cadmium levels. Renal cadmium accumulation tended to be greater in females than in males who were in the same age range and who had similar lung-cadmium levels, a result that suggested that there was a higher absorption rate of cadmium in females. The mean value for a urinary cadmium excretion of 2.30 μg/gm creatinine was found in a subset of samples that had a mean age of 39 yr and a renal cortex cadmium concentration of 18.6 μg/gm wet tissue weight. Urinary cadmium excretion rates were correlated more strongly with lung and kidney cadmium content than with age or liver cadmium levels. The results suggest that urinary cadmium excretion may be increased in smokers and could provide some estimate of body cadmium burdens in future Australian epidemiological studies. Key Words: cadmium body burdencigarette smokedietary cadmiumexposure assessmenthuman autopsymetal toxicity
As an orally administered, locally acting gastrointestinal drug, mesalamine products are designed to achieve high local drug concentration in the gastrointestinal (GI) tract for the treatment of ulcerative colitis. The aim of this study was to directly measure and compare drug dissolution of three mesalamine formulations in human GI tract and to correlate their GI concentration with drug concentration in plasma. Healthy human subjects were orally administered Pentasa, Apriso, or Lialda. GI fluids were aspirated from stomach, duodenum, proximal jejunum, mid jejunum, and distal jejunum regions. Mesalamine (5-ASA) and its primary metabolite acetyl-5-mesalamine (Ac-5-ASA) were measured using LC–MS/MS. GI tract pH was measured from each GI fluid sample, which averaged 1.82, 4.97, 5.67, 6.17, and 6.62 in the stomach, duodenum, proximal jejunum, middle jejunum, and distal jejunum, respectively. For Pentasa, high levels of 5-ASA in solution were observed in the stomach, duodenum, proximal jejunum, mid jejunum, and distal jejunum from 1 to 7 h. Apriso had minimal 5-ASA levels in stomach, low to medium levels of 5-ASA in duodenum and proximal jejunum from 4 to 7 h, and high levels of 5-ASA in distal jejunum from 3 to 7 h. In contrast, Lialda had minimal 5-ASA levels from stomach and early small intestine. A composite appearance rate (CAR) was calculated from the deconvolution of individual plasma concentration to reflect drug release, dissolution, transit, and absorption in the GI tract. Individuals dosed with Pentasa had high levels of CAR from 1 to 10 h; individuals dosed with Apriso had low levels of CAR from 1 to 4 h and high levels of CAR from 5 to 10 h; Lialda showed minimal levels of CAR from 0 to 5 h, then increased to medium levels from 5 to 12 h, and then decreased to further lower levels after 12 h. In the colon region, Pentasa and Apriso showed similar levels of accumulated 5-ASA excreted in the feces, while Lialda showed slightly higher 5-ASA accumulation in feces. However, all three formulations showed similar levels of metabolite Ac-5-ASA in the feces. These results provide direct measurement of drug dissolution in the GI tract, which can serve as a basis for investigation of bioequivalence for locally acting drug products.
Purpose: Dyssynergia Defecation (DD) is an underrecognized cause of chronic constipation (CC). DD occurs when a patient is unable to coordinate the abdominal wall muscles, puborectalis/anorectal angle, anal sphincter and pelvic floor in a manner which allows the normal passage of stool from the rectum. Though constipation related complaints such as reduced stool frequency, straining and a sensation of incomplete evacuation are common, DD patients also commonly endorse abdominal symptoms such discomfort, pain, cramping, and bloating. Whether abdominal symptoms improve with biofeedback training in DD patients is unclear. We aimed to assess the impact of biofeedback therapy on abdominal symptoms including discomfort, pain, cramping and bloating in DD patients. Methods: A retrospective analysis of prospectively collected data from 65 manometrically proven DD patients who received biofeedback therapy at a tertiary center between 2008 and 2012. Each patient completed the 12 item Patient Assessment of Constipation (PAC-SYM) symptom questionnaire during their initial and discharge visits. The PAC-SYM measures abdominal complaints, rectal and stool domains related in CC patients. Paired sample t-tests were performed on the summations of the PAC-SYM and for each of the 12 individual items. P-values less than 0.05 were considered statistically significant. Results: The mean age of the sample was 54 years. Over 70% of participants were female and Caucasian. Bowel related and abdominal symptoms were commonly reported by DD patients. There was a highly significant reduction in initial total PAC-SYM score (22.8) and the PAC-SYM score following PT (12.1) (p<0.001). While all bowel and stool related domains significantly improved, substantial benefits for abdominal symptoms were also observed (See Table 1).Table: Effect of biofeedback on abdominal symptomsConclusion: Patients with dyssynergic defecation commonly report abdominal symptoms. Like bowel related symptoms, abdominal symptoms such as discomfort, pain and bloating significantly improve following biofeedback training.
