Pyrazole derivative Z10 ameliorates acute pancreatitis by inhibiting the ERK/Ddt pathway.

Acute pancreatitis (AP) can lead to death; however, there is no specific treatment for AP. Screening of drugs for AP treatment is rarely performed. Compounds were screened in a primary pancreatic acinar cell and peritoneal macrophage coculture system. Compounds were used in vitro and in vivo. Compound targets were predicted and validated. Among the 18 nitrogen-containing heterocycles, Z10 was shown to decrease the cerulein plus lipopolysaccharide (CL)-induced secretion of both acinar digestive enzymes and macrophage cytokines. Z10 was also shown to ameliorate CL-induced or sodium taurocholate-induced AP in mice. Proteomics analysis and enzyme linked immunosorbent assay (ELISA) revealed that Z10 decreased the levels of D-dopachrome tautomerase (Ddt) within macrophages and those in the extracellular milieu under CL treatment. Z10 also decreased Ddt expression in AP mice. Moreover, exogenous Ddt induced cytokine and digestive enzyme secretion, which could be inhibited by Z10. Ddt knockdown inhibited CL-induced cytokine secretion. Medium from CL-treated macrophages induced the release of amylase by acinar cells, and Ddt knockdown medium decreased amylase secretion. The target of Z10 was predicted to be ERK2. Z10 increased the thermostability of ERK1/2 but not ERK1 K72A/ERK2 K52A. The docking poses of ERK1 and ERK2 with Z10 were similar. Z10 inhibited ERK1/2 phosphorylation, and Ddt levels and cytokines were regulated by ERK1/2 during AP. Additionally, Z10 could not further inhibit cytokines under ERK1/2 knockdown with CL. Thus, this study revealed that Z10-mediated ERK1/2 inhibition decreased Ddt expression and secretion by macrophages. Ddt inhibition decreased cytokine release and digestive enzyme secretion.

miR-455-3p ameliorates pancreatic acinar cell injury by targeting Slc2a1.

Objective: With the number of patients with acute pancreatitis (AP) increasing year by year, it is pressing to explore new key genes and markers for the treatment of AP. miR-455-3p/solute carrier family 2 member 1 (Slc2a1) obtained through bioinformatics analysis may participate in the progression of AP. Materials and Methods: The C57BL/6 mouse model of AP was constructed for subsequent studies. Through bioinformatics analysis, the differentially expressed genes related to AP were screened and hub genes were identified. A caerulein-induced AP animal model was constructed to detect the pathological changes of mouse pancreas by HE staining. The concentrations of amylase and lipase were measured. Primary mouse pancreatic acinar cells were isolated and subjected to microscopy to observe their morphology. The enzymatic activities of trypsin and amylase were detected. The secretion of inflammatory cytokines in mouse were measured with the ELISA kits of TNF-α, IL-6 and IL-1ß to determine pancreatic acinar cell damage. A binding site between the Slc2a1 3' UTR region and the miR-455-3p sequence was verified by dual-luciferase reporter assay. The expression of miR-455-3p was quantified by qRT-PCR, and Slc2a1 were detected by western blot. Results: A total of five (Fyn, Gadd45a, Sdc1, Slc2a1, and Src) were identified by bioinformatics analysis, and miR-455-3p/Slc2a1 were further studied. HE staining results showed that the AP models were successfully established by caerulein induction. In mice with AP, the expression of miR-455-3p was reduced, while that of Slc2a1 was increased. In the caerulein-induced cell model, the expression of Slc2a1 was significantly reduced after intervention of miR-455-3p mimics, whereas increased after miR-455-3p inhibitor treatment. miR-455-3p decreased the secretion of inflammatory cytokines in the cell supernatant, reduced the activity of trypsin and amylase, and alleviated the cell damage induced by caerulein. In addition, Slc2a1 3'UTR region was bound by miR-455-3p, and its protein expression was also regulated. Conclusion: miR-455-3p alleviated caerulein-induced mouse pancreatic acinar cell damage by regulating the expression of Slc2a1.

Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report.

BACKGROUND: Valproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. Here, we present a case of VPA-induced pancreatitis in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms. He had no distinctive abdominal symptoms. CASE PRESENTATION: A 66-year-old Japanese man was treated with VPA for agitation and violent behavior due to vascular dementia, epileptic seizures, and psychiatric symptoms. During admission, he experienced a sudden decrease in consciousness and blood pressure. Abdominal findings were unremarkable; however, blood tests showed an inflammatory response and elevated amylase levels. Contrast-enhanced abdominal computed tomography showed diffuse pancreatic enlargement and inflammation extending to the subrenal pole. VPA-induced acute pancreatitis was diagnosed, VPA was discontinued, and high-dose infusions were administered. Acute pancreatitis resolved after treatment initiation. CONCLUSIONS: Clinicians should be aware of this relatively rare side effect of VPA. Diagnosis may be challenging in elderly people and patients with dementia as they may present with non-specific symptoms. Clinicians should consider the risk of acute pancreatitis when using VPA in patients who cannot report spontaneous symptoms. Blood amylase and other parameters should be measured accordingly.

Favorable efficacy of adalimumab treatment in experimental acute pancreatitis model.

BACKGROUND: Acute pancreatitis is a clinical picture with a wide range of symptoms from mild inflammation to multiorgan failure and death. The aim of this study is to investigate the effects of Adalimumab (ADA) on inflammation and apoptosis in a cerulein-induced acute pancreatitis model in rats. METHODS: Experimental cerulein-induced acute pancreatitis model was created by applying 4 intraperitoneal cerulein injections at 1-h intervals. A total of 40 rats, 8 in each group, were randomly distributed into five groups. In the groups that ADA treatment was given, two different doses of ADA were administered 5 mg/kg and 20 mg/kg as low and high doses, respectively. The rats were sacrificed 12 h after the last intraperitoneal administration of ADA. Blood samples were obtained from each rat for amylase, IL-6, and IL-1ß measurements. Hematoxylin and Eosin (H&E) stains were used to undertake the histopathological analysis of the pancreas. The terminal deoxynucleotidyl transferase-mediated nick-end-labeling (TUNEL) method was used to evaluate apoptosis. RESULTS: : Plasma amylase, IL-6, and IL-1ß levels were significantly elevated in acute pancreatitis groups (p < 0.05). It was determined that both low (5 mg/kg) and high doses (20 mg/kg) of ADA ameliorated the parameters (plasma amylase, IL-6, and IL-1ß) (p < 0.05). Although significant improvements were detected in the Schoenberg scoring system and the apoptotic index from the TUNEL method after highdose ADA treatment, no significant amelioration was observed in the histopathological examinations in the low-dose ADA group. DISCUSSION: : It has been determined that the administration of high-dose ADA effectively alleviated the symptoms of acute pancreatitis and reduced the level of apoptosis. In line with the findings of our study, we have predicted that high-dose (20 mg/kg) ADA can be used as an effective and safe drug in the treatment of patients with acute pancreatitis.

Independent and synergistic activity of the flavonoids of Gracilaria corticata as promising antidiabetic agents

The therapeutic approaches for Type 2 Diabetes Mellitus rely most on the usage of oral hypoglycaemic drugs. These drugs have adverse side effects and hence alternative medicines are continuously explored. The present study intends to investigate the antidiabetic potential of the flavonoids present in Gracilaria corticata. The flavonoids were isolated (FEGC) and their inhibitory activity on the carbohydrate hydrolysing enzymes such as α-amylase and α-glucosidase was analysed. The flavonoids were found to inhibit α-amylase and α-glucosidase with an IC50 value of 302 µg and 75 µg respectively. The synergistic effect of FEGC and luteolin was also investigated and the results show that both FEGC and luteolin inhibited synergistically at half their IC50 values. The observations of this study reveal that the flavonoids of G. corticata have potential antidiabetic activity and can act independently or synergistically in the management of Type 2 Diabetes Mellitus

Liprotamase long-term safety and support of nutritional status in pancreatic-insufficient cystic fibrosis.

OBJECTIVES: Patients with cystic fibrosis (CF) who have exocrine pancreatic insufficiency (EPI) require treatment with pancreatic enzyme replacement therapy (PERT) to maintain adequate nutrition and age-appropriate growth and weight gain. Liprotamase, a nonporcine, highly purified biotechnology-derived PERT, has demonstrated significant efficacy in fat and protein malabsorption in patients with EPI compared to placebo. This study of liprotamase is the first ever long-term trial of a PERT to evaluate safety and nutritional parameters. METHODS: This phase III 12-month open-label trial assessed the safety, tolerability, and long-term nutritional effects of liprotamase treatment in patients with CF and EPI 7 years and older. All of the patients were required to discontinue their long-term use of porcine PERTs at the time of enrollment. Dosing started at 1 capsule of liprotamase (32,500 US Pharmacopoeia (USP) units crystallized cross-linked lipase, 25,000 USP units crystallized protease, and 3,750 USP units amorphous amylase) per meal or snack; dose could be increased based on protocol-defined parameters. RESULTS: A total of 215 subjects were enrolled and 214 received at least 1 dose of liprotamase (mean 5.5 capsules per day). During the study period, height, weight, and body mass index z scores and lung function as measured by forced expiratory volume in 1 second were stable. There were no clinically meaningful changes in laboratory tests, including levels of fat-soluble vitamins. Liprotamase was well tolerated without any significant safety concerns. Adverse events, primarily gastrointestinal, led to treatment discontinuation for 36 subjects (16.8%), most within the first 3 months. CONCLUSIONS: Treatment with a mean of 5.5 capsules of liprotamase per day, during meals and snacks, for up to 12 months was safe, well tolerated, and associated with age-appropriate growth and weight gain or weight maintenance in subjects with CF-related EPI.

International phase III trial of liprotamase efficacy and safety in pancreatic-insufficient cystic fibrosis patients.

BACKGROUND: Most cystic fibrosis (CF) patients have exocrine pancreatic insufficiency (EPI) and need supplementation with pancreatic enzyme replacement therapy (PERT). Liprotamase, a novel non-porcine PERT containing highly purified biotechnology-derived lipase, protease, and amylase, has successfully undergone initial efficacy and safety testing. METHODS: In this international phase III parallel-group, randomized-withdrawal, double-blind placebo-controlled trial, CF patients with EPI 7 years and older, including nutritionally and functionally compromised individuals, underwent baseline testing for coefficients of fat and nitrogen absorption (CFA and CNA) and stool weight and frequency while off PERT. After an open-label treatment period with liprotamase, subjects were randomized 1:1 to one liprotamase or placebo capsule taken with 3 meals and 2 snacks per day. The dose was fixed and increases were not allowed. The same measurements were obtained again after treatment with double-blind study drug or placebo. RESULTS: 138 subjects were randomized. The adjusted least squares mean (LSM) difference between the treatment and placebo groups for change in CFA was 15.1% (p=0.001) for the subgroup with baseline CFA <40%, 8.6% (p=0.006) for subjects with baseline CFA ≥40%, and 10.6% (p<0.001) for the overall intent-to-treat population. Similar results were seen for change in CNA. Stool weight was significantly decreased although not stool frequency. Liprotamase was well tolerated with no safety concerns identified. CONCLUSIONS: In a CF patient population reflective of that encountered in clinical practice, this trial demonstrated that liprotamase at a fixed dose of one capsule per meal or snack (5 capsules per day) was well tolerated and significantly increased fat absorption as measured by improvement in CFA, significantly increased protein absorption as measured by improvement in CNA, and significantly decreased stool weight.

Risk factors associated with elevated serum pancreatic amylase levels during hemodialysis.

Elevated levels of serum pancreatic enzymes are frequently observed in hemodialysis (HD) patients. The complex hemodynamic, biochemical, and physiological alterations in uremia were speculated to cause excessive release of pancreatic enzymes beyond decreased renal clearance. However, hemodynamic factors are seldom explored in this aspect. We performed the study to evaluate the association between intradialytic hemodynamic change and elevated serum pancreatic amylase (SPA). Eighty-three prevalent HD patients without any clinical evidence of acute pancreatitis underwent pre-HD and post-HD blood sampling for serum pancreatic enzyme levels. Demographic, biochemical, and hematological data were collected from patient record review. Hemodialysis information including intradialytic blood pressure changes and ultrafiltration (UF) amount were collected and averaged for 1 month before the blood sampling day. Patients with elevated SPA during the HD session had greater mean systolic blood pressure and mean arterial pressure reduction, greater UF volume, greater pre-HD blood urea nitrogen and serum creatinine, higher serum phosphorus, lower pre-HD serum total CO2, and lower left ventricle ejection fraction (LVEF). Using multivariate linear and logistic regression analysis, the independent predictors of elevated SPA were determined to be mean arterial pressure reduction during HD, mean UF amount, pre-HD serum total CO2, and LVEF. Greater blood pressure reduction during HD, greater UF volume, lower pre-HD serum total CO2, and lower LVEF were significantly associated with elevated SPA during HD. This suggests that hemodynamic factors contribute to elevated serum pancreatic enzymes in HD patients.

Poly(ADP-ribose) polymerase inhibition modulates experimental acute necrotizing pancreatitis-induced oxidative stress, bacterial translocation and neopterin concentrations in rats.

Various studies have been performed to find out novel treatment strategies for acute necrotizing pancreatitis (ANP). Inhibition of poly(ADP-ribose) polymerase (PARP) is shown to reduce inflammation in several pathological conditions. We aimed to evaluate the efficacy of benzamide, a PARP inhibitor, in an experimental model of ANP. Thirty Sprague-Dawley rats were divided into three groups: sham-operated, ANP and ANP + benzamide groups. All groups except the sham-operated group were subjected to the ANP procedure, induced by infusing of 1 mL/kg of 3% sodium taurocholate into the common biliopancreatic duct. The ANP + benzamide group received 100 mg/kg/day benzamide intraperitoneally for a total of three days after induction of pancreatitis. The surviving animals were killed at the fourth day and the pancreas was harvested for biochemical, microbiological and histological analysis. Blood samples were also obtained from the animals. In the ANP group, a significant increase was observed in concentrations of serum amylase and neopterin and tissue oxidative stress indices (malondialdehyde, superoxide dismutase and glutathione peroxidase). Almost all of these changes were found to be reversed to near their normal values in the ANP + benzamide group. Histological injury scores were significantly higher in the ANP group than in the sham group (P < 0.05, ANP versus sham), and were significantly lower in the ANP + benzamide group than in the ANP group (P < 0.05, ANP + benzamide versus ANP). Evaluation of bacterial translocation identified significantly fewer infected sites in the ANP + benzamide group than in the ANP animals (P < 0.01). We observed that inhibition of PARP with benzamide reduced the severity, the mortality, the bacterial translocation rates and the neopterin concentrations in an experimental ANP model in rats. These findings suggest that it may be possible to improve the outcome of ANP by using PARP inhibitors.

Diástase dos músculos retos abdominais em puérperas na fase hospitalar / Diastasis of the rectus abdominis muscle in puerperium during hospitalization period

Introdução: Uma diástase do músculo reto abdominal (DMRA) de 3 cm ou mais em puérperas é considerada acima dos padrões de normalidade e poderão trazer maiores complicações como dores lombares, limitações funcionais e herniações das vísceras abdominais. Objetivo: Mensurar a DMRA em puérperas, na Maternidade do Hospital Satélite, e correlacionar com paridade, idade da puérpera, peso do recém nascido (RN) e sedentarismo. Material e métodos: Estudo transversal, observacional, com uma amostra de 30 puérperas, examinadas no mês de novembro de 2008 em relação à paridade, ao sedentarismo e ao peso do RN. Resultados: A multiparidade foi o que apresentou uma maior relação ao aumento de DMRA, quando comparada ao grupo primigestas/secundigestas (p = 0,003). A média da DMRA em sedentárias foi de 3,7 cm e para as não sedentárias foi de 2,8 cm (p < 0,05). O peso do RN tem influência de 11,47 por cento sobre a diástase (p < 0,067). A variável que mais evidenciou uma correlação positiva com o aumento da DMRA foi a faixa etária da gestante com influência de 42,99 por cento sobre DMRA (p < 0,008).Conclusão: A paridade, a prática de atividade física, o peso do RN e, principalmente, a idade da gestante influenciam diretamente na variação do tamanho da DMRA durante o período de gestação.

Introduction: A diastasis recti of the rectus abdominis muscle (RAMD) of 3 cm width or more is considered out of the acceptable patterns and can cause other commitments such as back pain, functional limitations and abdominal visceral herniation. Objective: To measure the RAM in post childbirth woman at the Maternity of Satélite Hospital in Teresina, Piauí, Brazil, and to correlate it to parity, mother’s age at delivery, newborn weight and sedentarism. Method: This was a transversal and observational study with 30 women examined at immediate post-partum on November 2008 in terms of parity, sedentarism and newborn weight. Results: High parity factor showed a higher relation to the diastase increase when was compared first pregnancy and second pregnancy group (p = 0.003). The average of RAMD in sedentary women was 3.7 cm comparing to 2.8 cm in non-sedentaries (p < 0.05). The newborn weight has 11.47 percent of influence over diastase (p < 0,067). The variable that most influenced with a positive correlation with RAMD was the mother age at delivery (42.99 percent over RAMD, p < 0.008). Conclusion: Parity, physical activity, newborn weight and, mainly, age of pregnant woman are factors that influence RAMD size range during pregnancy.

Study of a novel pancreatic enzyme replacement therapy in pancreatic insufficient subjects with cystic fibrosis.

OBJECTIVES: We studied a novel pancreatic enzyme product, ALTU-135, a proprietary formulation of microbially derived lipase, protease, and amylase, to determine its efficacy and safety in treatment of pancreatic insufficiency (PI) in patients with cystic fibrosis (CF). STUDY DESIGN: Ambulatory subjects with CF-PI (n = 117) had baseline coefficient of fat and nitrogen absorption (CFA and CNA, respectively) determined in an inpatient setting while not receiving pancreatic enzyme replacement therapy. Subjects were then randomized to treatment with ALTU-135 containing 5000 (low), 25,000 (mid), or 100,000 (highest) units of lipase (1:1:0.15 of lipase:protease:amylase) for 28 days. After 14 days, CFA and CNA were re-measured. The primary outcomes were change from baseline in CFA and CNA between treatments. RESULTS: Treatment CFA was significantly greater in the mid and highest dose groups compared with that in the low dose group (P = .0229 and P =.0041, respectively); findings were similar for CNA. Subjects with baseline CFA < or = 40% and > 40% in the 2 higher dose groups had a mean increase of 31 and 8 percentage points in CFA, respectively (P < .0001). CONCLUSION: ALTU-135 was efficacious during the 1-month study period at the dose of 25,000 units of lipase, 25,000 units of protease, and 3750 units of amylase.

Safety and preliminary clinical activity of a novel pancreatic enzyme preparation in pancreatic insufficient cystic fibrosis patients.

OBJECTIVES: Currently available pancreatic enzyme products are crude porcine products with few data available regarding their efficacy, safety, and manufacture. We conducted a phase 1 study of a novel pancreatic enzyme product, TheraCLEC-Total (TCT), a proprietary formulation of microbial-derived lipase, protease, and amylase, to determine its safety and preliminary efficacy in cystic fibrosis. METHODS: We conducted an open-label, dose-ranging study in 23 subjects diagnosed with pancreatic insufficiency with cystic fibrosis. The subjects received TCT containing lipase dose of 100, 500, 1000, 2500, or 5000 USP U/kg per meal with each meal or snack for 3 days. The clinical and laboratory parameters and adverse events (AEs) were monitored. RESULTS: There were no serious AEs. Most AEs were mild, although gastrointestinal complaints were common. TCT increased the coefficient of fat and nitrogen absorption in all groups except in the low-dose group. At the other dosing levels, the mean coefficient of fat and nitrogen absorption increases were 19.1% +/- 24.9% and 17.8% +/- 13.6%, respectively, whereas the mean stool weight decreased by 517 +/- 362 g. CONCLUSIONS: TCT was well tolerated in this short-term exposure study. The preliminary efficacy data demonstrate lipase and protease activity with little difference seen with lipase doses greater than 500 USP U/kg per meal. These data support a larger randomized phase 2 trial.

Lack of type 1 sensitization to laundry detergent enzymes among consumers in the Philippines: results of a 2-year study in atopic subjects.

BACKGROUND: Enzymes have been safely used in laundry products for many years. The risk of developing adverse responses to enzymes in laundry detergents among consumers in countries where hand laundry predominates is expected to be low. OBJECTIVES: To understand how consumers in hand laundry markets used detergent products; to show that use of enzyme-containing detergents did not lead to sensitization in an atopic population with compromised skin; and to show that enzyme detergents did not have an adverse effect on skin condition. METHODS: Women in the rural Philippines were chosen since they do hand laundry for several hours a day, every day. The skin prick test (SPT) tested for the presence of IgE antibody to common aeroallergens and to enzymes in detergent product. Atopic women used enzyme-containing laundry bars for hand laundry and personal cleansing. They also used enzyme-containing laundry granules for hand laundry. All subjects were evaluated by SPT with enzymes over 2 years. Hand and body skin conditions were also evaluated. RESULTS: None of the 1,980 subjects screened for eligibility into the 2-year study were SPT positive to enzymes, including 655 women who used enzyme-containing detergent for up to 1 year. None of the subjects in the study developed IgE to the enzymes. Enzymes had no adverse effect on skin condition or on the development of erosions on the hands. CONCLUSIONS: The 2-year study confirms that enzymes are safe for use in laundry products at or below levels tested in the study even when used by atopic consumers under extremely harsh conditions.

An outbreak of asthma in a modern detergent factory.

The striking decrease in the occurrence of protease-induced occupational asthma in the detergent Industry has been attributed to enzyme encapsulation. We report an outbreak of asthma, at least equal in size to those reported in the 1960s, in a modem European factory which has exclusively used encapsulated enzymes. A survey revealed that enzyme sensitisation and work-related respiratory symptoms were positively correlated with airborne enzyme exposure. We suggest that encapsulation alone is insufficient to prevent enzyme-Induced allergy and asthma.

Occupational asthma caused by bacillary amylase used in the detergent industry.

Four cases are reported of occupational asthma due to amylase derived from Bacillus licheniformis, used in detergent washing powders. It is thought that these are the first reported cases of asthma due to this enzyme in the detergent industry. All four employees (men) were from the same factory and none had a history of asthma or atopy. All developed symptoms of wheeze at work after an initial symptom free period. Symptoms improved during periods away from work. All undertook serial peak flow recordings (not diagnostic) and underwent skin prick tests, radio allergosorbent test (RAST) measurement, and specific bronchial provocation testing. The bronchial provocation testing was performed by a dust tipping method in a single blind manner, with lactose as an inert control and powdered amylase, provided by the employer, as an active agent. Serial measurements of forced expiratory volume in 1 second (FEV(1)) were recorded and histamine provocative concentration causing a 20% fall in FEV(1) (PC(20)) tests were determined before and 24 hours after each challenge. Patient 1 developed an isolated early reaction, patient 2 an isolated late reaction, and patients 3 and 4 developed dual reactions. All showed an increased non-specific bronchial responsiveness after active challenge. The introduction of encapsulated enzymes in the detergent industry was followed by a reduction in the incidence of respiratory sensitisation. These patients developed occupational asthma despite working only with encapsulated enzymes. This highlights the importance of careful surveillance after the introduction of new agents in the workplace.

Respiratory symptoms and wheat flour exposure: a study of flour millers.

The objective of this study was to determine the prevalence of respiratory symptoms and their relationship to sensitization to wheat flour allergens and fungal amylase, in a group of workers from the UK flour milling industry. A cross-sectional study was used to evaluate symptoms, using a structured interview technique, and sensitization, using skin prick test findings, from 679 employees in flour milling and packing operations at 18 flour mills. A total of 147 workers (147/679, 22%) described upper respiratory tract symptoms of some kind. In the majority (139/147, 95%) these symptoms were of an occasional or transitory nature and were related to short-term exposures to high levels of dust. Three individuals (3/679, 0.4%) were identified whose symptoms were thought to be the result of allergy to wheat flour. The prevalence of positive skin prick tests to wheat flour allergens and to fungal amylase was 1.2% (8/678) and 0.9% (6/678), respectively. Measurements of total inhalable dust exposure for personnel exposed to flour dust were taken at 10 of the sites (116 samples). For production personnel the levels were typically between 1 and 10 mg/m3 (8-h time weighted average), with a median of 6.2 mg/m3. Hygiene operatives had appreciably higher exposure than production personnel, with a median of 18.7 mg/m3. Overall, 43% (50/116) of all samples exceeded 10 mg/m3 (8-h time weighted average). The findings suggest that the risk of sensitization to wheat flour allergens from current dust exposures in flour mills is very low. Wheat allergy was responsible in only a small proportion of the total who had respiratory symptoms. The principal causation of symptoms experienced by the workforce was considered to be a non-specific irritant effect related to short-term exposures to high levels of total inhalable dust.

Health surveillance in milling, baking and other food manufacturing operations--five years' experience.

The objective of this study was to describe the incidence of allergic respiratory disease and its outcome in terms of symptoms and jobs, across different flour-using industries. It uses the findings of a health surveillance programme in a large food organization over a five-year period. The population under surveillance consisted of 3,450 employees with exposure to ingredient dusts, of whom 400 were in flour milling, 1,650 in bread baking, 550 in cake baking and 850 in other flour-using operations. A total of 66 employees with either asthma or rhinitis symptoms attributable to sensitization to allergens in the workplace were identified. The majority of these (48/66) had become symptomatic prior to the commencement of the health surveillance programme in 1993. The incidence rates (per million employees per year) for those who developed symptoms between 1993 and 1997 were 550 for flour milling, 1,940 for bread baking, 0 for cake baking and 235 for other flour-using operations. The agent believed to be responsible for symptoms was most commonly grain dust in flour millers and fungal amylase in bread bakers. Wheat flour appeared to have a weaker sensitizing potential than these other two substances. In terms of outcome, at follow-up 18% of symptomatically sensitized employees had left the company. Two of the ex-employees retired through ill health due to occupational asthma. Of those still in employment, 63% described an improvement in symptoms, 32% were unchanged and 4% were worse than when first diagnosed. Over half the cases still in employment were continuing to work in the same job as at the time of diagnosis.