Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new pancrease research articles will be listed here shortly after becoming available to us.
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Medical research on pancrease
Cancer prevention by tea and tea polyphenols.
Asia Pac J Clin Nutr. 2008; 17 Suppl 1: 245-8
Yang CS, Ju J, Lu G, Xiao H, Hao X, Sang S, Lambert JD
The inhibition of tumorigenesis by tea extracts and tea polyphenols has been demonstrated in different animal models, including those for cancer of the skin, lung, oral cavity, esophagus, stomach, small intestine, colon, bladder, liver, pancrease, prostate, and mammary glands. Caffeine is also active in inhibition of tumorigenesis on the skin, lung, and perhaps other organs. In spite of many in vitro and in vivo studies, the molecular mechanisms for the cancer preventive actions of these compounds are not clearly known. The relationship between tea consumption and cancer risk has not been conclusively demonstrated, and the relationship may become more clear if we consider the effects of specific types of tea, at defined doses, in populations with certain dietary patterns or genetic polymorphisms. Human intervention trials and large prospective studies are needed to further assess the cancer preventive activities of tea constituents.
Insulin receptor and lipid metabolism pathology in ataxin-2 knock-out mice.
Hum Mol Genet. 2008 May 15; 17(10): 1465-81
Lastres-Becker I, Brodesser S, Lütjohann D, Azizov M, Buchmann J, Hintermann E, Sandhoff K, Schürmann A, Nowock J, Auburger G
Ataxin-2 is a cytoplasmic protein, product of the SCA2 gene. Expansion of the normal polyglutamine tract in the protein leads to the neurodegenerative disorder Spino-Cerebellar Ataxia type 2 (SCA2). Although ataxin-2 has been related to polyribosomes, endocytosis and actin-cytoskeleton organization, its biological function remains unknown. In the present study, an ataxin-2 deficient mouse (Sca2(-/-)) was generated to investigate the functional role of this protein. Homozygous mice exhibited reduced fertility and locomotor hyperactivity. In analyses up to the age of 6 months, the absence of ataxin-2 led to abdominal obesity and hepatosteatosis. This was associated with reduced insulin receptor expression in liver and cerebellum, although the mRNA levels were increased indicating a post-transcriptional effect of ataxin-2 on the insulin receptor status. As in insulin resistance syndromes, insulin levels were increased in pancreas and blood serum. In the cerebellum, increased levels of gangliosides and sulfatides, as well as decreased cholesterol dynamics, may be relevant for cellular membrane functions, and alterations in the sphingomyelin cycle may affect second messengers. Thus, the data suggest altered signaling in ataxin-2 deficient organisms.
Cell Metab. 2008 Jan; 7(1): 57-67
Speidel D, Salehi A, Obermueller S, Lundquist I, Brose N, Renström E, Rorsman P
CAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolerant and that this effect is attributable to a marked reduction of glucose-induced insulin secretion. This correlates with diminished Ca(2+)-dependent exocytosis, a reduction in the size of the morphologically docked pool, a decrease in the readily releasable pool of secretory vesicles, slowed granule priming, and suppression of second-phase (but not first-phase) insulin secretion. In beta cells of CAPS1(+/-);CAPS2(-/-) mice, the lowered insulin content and granule numbers were associated with an increase in lysosome numbers and lysosomal enzyme activity. We conclude that although CAPS proteins are not required for Ca(2+)-dependent exocytosis to proceed, they exert a modulatory effect on insulin granule priming, exocytosis, and stability.
Effect of liquid pancreatic enzymes on the assimilation of fat in different liquid formula diets.
JPEN J Parenter Enteral Nutr. 2008 Jan-Feb; 32(1): 98-100
Hauenschild A, Ewald N, Klauke T, Liebchen A, Bretzel RG, Kloer HU, Hardt PD
BACKGROUND: In some diseases, patients require high-calorie tube feeding with standard enteral formulas usually administered via temporal feeding tubes. One frequent pathophysiological condition in a relevant number of these patients is exocrine pancreatic insufficiency. Patients unable to swallow capsules might benefit from a liquid pancreatic enzyme (LPE) preparation. METHODS: LPEs were prepared and mixed with different commercially available formula diets produced for enteral feeding. Lipolysis was then measured by fatty acid titration. RESULTS: Complete lipolysis by liquid enzyme preparations was observed in diverse formula diets. Fat assimilation was even complete when LPE had been prepared 3.5 hours before the experiments, showing that the enzymes had been stable up to that time. CONCLUSIONS: The use of LPEs seems to be a good therapeutic option in patients with exocrine pancreatic insufficiency and the need for permanent high-calorie enteral feeding. Pharmaceutical companies should therefore be further encouraged to develop and distribute liquid enzyme preparations.
Rapid Commun Mass Spectrom. 2008; 22(2): 121-9
Pulkkinen M, Palmgrén JJ, Auriola S, Malin M, Seppälä J, Järvinen K
This paper describes a straightforward and rapid on-line characterization using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS(n)) of the enzymatic degradation products of 2,2'-bis(2-oxazoline)-linked poly-epsilon-caprolactone (PCL-O). These new PCL-O polymers are expected to be used in a variety of pharmaceutical and biomedical applications since they are degraded enzymatically by surface erosion. PCL-O was polymerized in a three-step reaction and characterized by (1)H-NMR and size-exclusion chromatography (SEC). Solvent cast polymer films were exposed to enzymatic degradation in phosphate buffer (pH 7.5, 1% pancreatin). The enzymatic degradation of the polymer produced a wide variety of water-soluble oligomers which were separated and identified by HPLC/ESI-MS(n). Optimization of the gradient HPLC method resulted in effective separation of the oligomers. Furthermore, specific structures of the oligomers were clearly identified by tandem mass spectrometry. According to these results, ester bonds seem to be most sensitive to enzymatic degradation and, correspondingly, pancreatic lipase seems to be mainly responsible for the enzymatic erosion of the PCL-O films. This novel mass spectrometric method provides important knowledge about the enzymatic degradation process and structure of the polymer which is difficult to ascertain by other conventional methods.
New concepts in the management of adverse drug reactions.
Allergy Asthma Proc. 2007 Sep-Oct; 28(5): 517-24
Bahna SL, Khalili B
Our understanding of drug reactions and their management has changed markedly in recent years with the development of several new concepts. Epidermal cell death seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may result from Fas-Fas ligand-mediated apoptosis. Intravenous immunoglobulin (IVIG) contains anti-Fas antibodies that can abrogate apoptosis. Most studies on IVIG in SJS and TEN reported improvement in arresting disease progression and reduction in time to healing. Furthermore, several studies have dispelled the myth of sulfonamide cross-reactivity. Immune-mediated reactions against antibacterial sulfonamides are directed against two unique side chains that non-antibacterial sulfonamides do not contain. Certain patients seem to have a genetic predisposition for "multiple drug sensitivities." Hence, they may react to several drugs that are not necessarily cross-reacting. Also, multiple studies have shown that IgE-mediated nonsteroidal anti-inflammatory drugs (NSAIDs) cross-reactivity is uncommon. Rather, it is cyclooxygenase (COX) 1 inhibition that results in pseudoallergic reactions to multiple NSAIDs. Several studies have indicated that selective COX-2 inhibitors can be safely administered in patients with aspirin-exacerbated respiratory disease and NSAID-induced cutaneous reactions, although their use has been curtailed by their cardiovascular side effects. Biological agents, such as infliximab, are being increasingly used for a variety of diseases and have caused adverse reactions in some patients. Studies differ as to whether concomitant immunosuppressive use with infliximab affects the development of drug-specific antibodies and infusion reactions. Successful desensitization protocols have been developed for reactions to some of these agents.
[Management of nonfunctioning islet cell tumors of the pancreas]
Zhonghua Zhong Liu Za Zhi. 2007 Jun; 29(6): 457-60
Liang H, Wang XN, Wang BG, Pan Y, Ding XW, Hao XS
OBJECTIVE: To analyze the clinical and pathological features in order to investigate appropriate way of diagnosis and treatment for non-functional islet cell tumors of the pancreas (NFICT). METHODS: The data and experience of surgically treated 43 patients with pathologically confirmed NFICT over the last 30 years were retrospectively reviewed. The survival rate was estimated using Kaplan-Meier method and the potential risk factors affecting survival were compared with Log rank test. RESULTS: There were 7 males and 36 females in this series with a mean age of 31.6 years ranged from 8 to 67 years. Twenty-eight patients were diagnosed as having non-functional islet cell carcinomas of the pancreas (NFICC) and 15 patients benign islet cell tumors. The most common symptoms in NFICT were abdominal pain 55.8%, nausea and/or vomiting (32.6%), fatigue (25.6%) and abdominal mass (23.3%). Preoperatively, all of those were found to have a mass in their pancrease by ultrasonic and computed tomography examination, with 21 in the head, 10 in the body and 6 in the tail of the pancreas. Multicemtric tumor were found in one patient. Thirty-nine of these 43 patients (90.7%) underwent surgical resection, with a curative resection in 30 (69.8%) and palliative in 9 (20.9%). The resectability and curative resection rate in 28 patients with nonfunctioning islet cell carcinomas of the pancreas was 78.6% and 60.7%, respectively. None of the 15 patients with benign nonfunctioning islet cell tumor of the pancreas died of this disease. While the overall cumulative 5- and 10-year survival rate in 28 patients with non-functional islet cell carcinomas of the pancreas was only 58.1% and 29.0%, respectively. Curative resection, female, younger than 30 years old and mass diameter < 10 cm were found to be positive prognostic factors. But multivariate Cox regression analysis indicated that radical resection was the only independent prognostic factor (P = 0.007). CONCLUSION: Nonfunctioning islet cell tumor of the pancreas is frequently found in young female. Surgical resection, especially curative resection can achieve satisfactory long-term survival.
Aliment Pharmacol Ther. 2008 Feb 1; 27(3): 283-92
Aloulou A, Puccinelli D, Sarles J, Laugier R, Leblond Y, Carrière F
BACKGROUND: Various pancreatic enzyme preparations are used for the treatment of pancreatic insufficiency but their bioequivalence is often unknown. AIM: To determine in vitro the pH-dependent release and acid resistance of enzymes from three commercially available pancreatin capsules, two containing enteric-coated (Creon 25000; Eurobiol 25000) and one uncoated (Eurobiol 12500) microspheres. METHODS: Dissolution experiments were performed at pH values ranging from 4.0 to 5.8. Lipase, chymotrypsin and amylase activities were measured in the solution as a function of time. RESULTS: Eurobiol 25000 started to release its enzymes significantly at pH 5.0 (t(1/2) = 71 min), whereas the enzymes from Creon 25000 were only released at higher pH value (5.4; t(1/2) = 49.2 min). Unlike chymotrypsin, lipase and amylase were highly sensitive to acidic conditions at the lowest pH values tested. Both enzymes were also found to be sensitive to proteolytic inactivation at the highest pH values tested. Overall, Eurobiol 25000 released higher amounts of active amylase and lipase than Creon 25000 at the pH values usually found in duodenal contents. The uncoated Eurobiol 12500 preparation was, however, the only one that could immediately release rather high levels of active chymotrypsin and lipase at low pH (4.5). CONCLUSION: These findings suggest that pH-sensitive enteric-coated pancreatin products containing similar amounts of enzymes might not be bioequivalent depending on the pH of duodenal contents.
Yakugaku Zasshi. 2007 Oct; 127(10): 1715-21
Gao D, Li Q, Liu Z, Li Y, Liu Z, Fan Y, Li K, Han Z, Li J
Cortex Lycii Radicis (CLR) has been used as a traditional Oriental medicine as an antipyretic and to treat pneumonia, night-sweats, cough, hematemesis, inflammation, and diabetes mellitus for centuries. This study aimed to determine the effects of CLR on alloxan-induced diabetic mice and its mechanisms. Based on thin-layer chromatography (TLC) assay, the main compounds of CLR include an organic acid, flavone, alkaloid, polysaccharide, anthraquinone, and saponin. The mice were divided into four groups: normal control (NC), diabetes control (DC), diabetes+high-dose CLR (200 mg kg(-1)), and diabetes+low-dose CLR (100 mg kg(-1)). The diabetic mice were administered CLR daily for 28 days. The CLR treatment resulted in significant decreases in fasting blood glucose, total cholesterol, and triglycerides. CLR also showed a tendency to improve body weight gain in diabetic mice. Furthermore, the serum insulin level of each group was assayed, and the DC group had a lower serum insulin level than the NC group. Insulin levels were dose dependently raised in the CLR-treated groups compared with the DC group. According to single-cell gel electrophoresis and LD(50) analysis, CLR was nontoxic to the animals. The results indicate that CLR alleviates the blood glucose and lipid increases associated with diabetes and improves the abnormal glucose metabolism and increases insulin secretion by restoring impaired pancrease beta-cells in alloxan-induced diabetic mice. The results suggest that CLR has hypoglycemic potential and could be useful in diabetes therapy.
Pancreatic enzyme pharmacotherapy.
Pharmacotherapy. 2007 Jun; 27(6): 910-20
Ferrone M, Raimondo M, Scolapio JS
Supplemental pancreatic enzyme preparations are provided to patients with conditions of pancreatic exocrine deficiency such as chronic pancreatitis and cystic fibrosis. These patients frequently experience steatorrhea, which occurs from inadequate fat absorption. The delivery of sufficient enzyme concentrations into the duodenal lumen simultaneously with meals can reduce nutrient malabsorption, improve the symptoms of steatorrhea, and in some cases alleviate the pain associated with chronic pancreatitis. Current clinical practices dictate administration of lipase 25,000-40,000 units/meal by using pH-sensitive pancrelipase microspheres, along with dosage increases, compliance checks, and differential diagnosis in cases of treatment failure. Despite the large number of specialty enzyme replacements available commercially, many patients remain dissatisfied with standard therapy, and future developments are needed to optimize treatment in these individuals.