Effect of oral or injectable supplementation with cobalamin in dogs with hypocobalaminemia caused by chronic enteropathy or exocrine pancreatic insufficiency.

BACKGROUND: Recent studies have shown similar efficacy of oral supplementation of cobalamin compared to injectable supplementation in dogs, but few prospective, randomized studies have been published. OBJECTIVES: To evaluate efficacy of oral or injectable supplementation with cobalamin in normalizing serum cobalamin and methylmalonic acid (MMA) concentrations in dogs with hypocobalaminemia caused by either chronic enteropathy (CE) or exocrine pancreatic insufficiency (EPI). ANIMALS: Forty-six client owned dogs with hypocobalaminemia. METHODS: Prospective randomized clinical trial. Dogs were divided into 2 groups (CE or EPI), and randomized to receive oral or injectable supplementation of cobalamin. Each dog had 3 visits and serum cobalamin and MMA concentrations were measured at each visit. RESULTS: In dogs with CE, serum cobalamin concentrations increased with oral (P = .02; median 149 [range 149-231] to 733 [166-1467] ng/L, median difference 552 [95% CI: 181-899] ng/L) or injectable (P < .01; 168 [149-233] to 563 [234-965] ng/L, 367 [187-623] ng/L) supplementation. In dogs with EPI, serum cobalamin concentrations increased with oral (P = .01; 162 [149-214] to 919 [643-3863] ng/L, 705 [503-3356] ng/L) or injectable (P = .01; 177 [149-217] to 390 [243-907] ng/L, 192 [89-361] ng/L) supplementation. Serum MMA concentrations decreased with oral or injectable supplementation in dogs with CE, but only with oral supplementation in dogs with EPI. CONCLUSIONS AND CLINICAL IMPORTANCE: Oral supplementation is an alternative for cobalamin supplementation in dogs with hypocobalaminemia caused by CE or EPI.

Effects of oral cobalamin supplementation on serum cobalamin concentrations in dogs with exocrine pancreatic insufficiency: A pilot study.

The objective of this retrospective study was to evaluate serum cobalamin concentrations before and after oral cobalamin supplementation in dogs with low serum cobalamin concentrations and exocrine pancreatic insufficiency (EPI). Eighteen dogs with serum trypsin-like immunoreactivities between <1.0-2.7 µg/L (reference interval, 5.2-35 µg/L) and serum cobalamin concentrations ≤350 ng/L (reference interval, 244-959 ng/L) were enrolled. All dogs were treated with oral cyanocobalamin according to a previously described protocol (0.25-1.0 mg daily, depending on bodyweight). Median (range) serum cobalamin concentrations at inclusion was 188 ng/L (<111-350 ng/L), which increased significantly to 1000 ng/L (794-2385 ng/L; P < 0.001) after cobalamin supplementation for 19-199 days (median, 41 days). Oral cobalamin supplementation is a potential alternative to parenteral supplementation in dogs with EPI.

[The effectiveness of pancreatic enzyme replacement therapy using microencapsulated pancreatin preparations in the correction of nutritional status in patients with chronic pancreatitis: a prospective observational study].

AIM: The goal is to evaluate the effectiveness of pancreatic enzyme replacement therapy (PERT) using microencapsulated pancreatin preparations for the correction of nutritional status in patients with chronic pancreatitis (CP) and associated exocrine pancreatic insufficiency (EPI). MATERIALS AND METHODS: The study included 58 patients with CP who were divided into two groups depending on the results of a laboratory assessment of indicators of nutritional status: group I (n=30) consisted of patients with CP and signs of EPI (according to low elastase test values) without deviations in nutritional status; Group II (n=28) consisted of patients with CP with a EPI and an abnormal nutritional status. In both groups, patients during the entire observation period (8-12 months) received PERT using microencapsulated pancreatin preparations at a dose adjusted for the severity of permanent residence permit. Before and after the PERT course, the dynamics of anthropometric [body weight, body mass index (BMI)] and laboratory indicators of nutritional status (total protein, albumin, vitamins D and B12, transferrin, iron and magnesium) were evaluated. RESULTS: After the completion of PERT, a significant tendency towards an increase in BMI in patients was noted in both groups. In group I, this indicator increased from 21.45 [95% confidence interval (CI) 19.80-23.92] kg/m2 to 22.15 (95% CI 20.31-23.86) kg/m2, and in II group - from 19.22 (95% CI 18.33-21.99) kg/m2 to 22.0 (95% CI 19.97-24.08) kg/m2. At the same time, the duration of PERT (months) significantly correlated with the dynamics of the patient's body weight (r=0.4679; 95% CI 0.2384-0.6479, p=0.0002). When assessing laboratory markers of nutritional status after PERT, a general tendency was found to increase the levels of total protein, albumin, vitamin D, magnesium, transferrin, and iron in both groups, however, statistically significant differences in the dynamics were observed mainly in group II patients. So, the level of total protein in group II increased from 69.05 (95% CI 65.6717-70.9000) g/l to 72.8 (95% CI 71.1358-74.9000) g/l, vitamin D - from 10.6 (95% CI 32.8397-38.9603) ng/ml to 17.1 (95% CI 12.0166-23.6232) ng/ml, magnesium - from 0.72 ( 95% CI 0.6892-0.7825) mmol/L to 0.795 (95% CI 0.7692-0.8800) mmol/L, and transferrin from 2.91 (95% CI 2.1800-3.3656 ) g/l to 2.92 (95% CI 2.4000-3.5200) g/l. CONCLUSION: A prospective observational study demonstrated the effectiveness of PERT using microencapsulated pancreatin preparations in the correction of nutritional status in patients with CP.

Choline Supplementation in Cystic Fibrosis-The Metabolic and Clinical Impact.

BACKGROUND: Choline is essential for the synthesis of liver phosphatidylcholine (PC), parenchymal maintenance, bile formation, and lipoprotein assembly to secrete triglycerides. In choline deficiency, the liver accretes choline/PC at the expense of lung tissue, thereby impairing pulmonary PC homoeostasis. In cystic fibrosis (CF), exocrine pancreas insufficiency results in impaired cleavage of bile PC and subsequent fecal choline loss. In these patients, the plasma choline concentration is low and correlates with lung function. We therefore investigated the effect of choline supplementation on plasma choline/PC concentration and metabolism, lung function, and liver fat. METHODS: 10 adult male CF patients were recruited (11/2014⁻1/2016), and orally supplemented with 3 × 1 g choline chloride for 84 (84⁻91) days. Pre-/post-supplementation, patients were spiked with 3.6 mg/kg [methyl-D9]choline chloride to assess choline/PC metabolism. Mass spectrometry, spirometry, and hepatic nuclear resonance spectrometry served for analysis. RESULTS: Supplementation increased plasma choline from 4.8 (4.1⁻6.2) µmol/L to 10.5 (8.5⁻15.5) µmol/L at d84 (p < 0.01). Whereas plasma PC concentration remained unchanged, D9-labeled PC was decreased (12.2 [10.5⁻18.3] µmol/L vs. 17.7 [15.5⁻22.4] µmol/L, p < 0.01), indicating D9-tracer dilution due to higher choline pools. Supplementation increased Forced Expiratory Volume in 1 second percent of predicted (ppFEV1) from 70.0 (50.9⁻74.8)% to 78.3 (60.1⁻83.9)% (p < 0.05), and decreased liver fat from 1.58 (0.37⁻8.82)% to 0.84 (0.56⁻1.17)% (p < 0.01). Plasma choline returned to baseline concentration within 60 h. CONCLUSIONS: Choline supplementation normalized plasma choline concentration and increased choline-containing PC precursor pools in adult CF patients. Improved lung function and decreased liver fat suggest that in CF correcting choline deficiency is clinically important. Choline supplementation of CF patients should be further investigated in randomized, placebo-controlled trials.

Systematic Review of Exocrine Pancreatic Insufficiency after Gastrectomy for Cancer.

BACKGROUND: Survival rates after a total gastrectomy with adequate lymphadenectomy are improving, leading to a shift in outcomes of interest from survival to postoperative outcomes and symptoms. In this systematic review, we investigate gastrointestinal symptoms that occur after a gastrectomy in relation to exocrine pancreatic insufficiency and the effect of pancreatic exocrine enzyme supplementation on these symptoms. METHODS: Online databases PubMed, Embase, and Cochrane Library were systematically searched in accordance with the PRISMA guidelines. Studies that researched gastrointestinal symptoms, exocrine pancreatic function, and enzyme supplementation were identified and assessed. RESULTS: The search resulted in a total of 1,023 articles after exclusion of duplicates. After performing a thorough assessment, 4 studies were included for systematic review. Exocrine pancreatic insufficiency was investigated by 2 studies; the results showed a significant decrease of total exocrine pancreatic function of up to 76%. The other 2 studies investigated the effect of pancreatic enzyme supplementation and found minor improvement in fecal consistency and a decrease in high-degree steatorrhea. No differences in individual symptom scores were reported. CONCLUSION: Gastrointestinal symptoms such as steatorrhea, bloating, and dumping syndrome may be related to exocrine pancreatic function, initiated by total gastrectomy. Treatment with pancreatic enzymes had a minor positive effect on patients. It should be noted that these studies were of a small sample size and low quality. New and larger RCTs are necessary to either prove or disprove the benefit of pancreatic enzyme replacement therapy in the treatment of the gastrointestinal symptoms after total gastrectomy.

Feline Exocrine Pancreatic Insufficiency: A Retrospective Study of 150 Cases.

BACKGROUND: Little information is available about the clinical presentation and response to treatment of cats with exocrine pancreatic insufficiency (EPI). OBJECTIVES: To describe the signalment, clinical signs, concurrent diseases, and response to treatment of cats with EPI. ANIMALS: One hundred and fifty cats with EPI. METHODS: Retrospective case series. RESULTS: Questionnaires were sent to 261 veterinarians, and 150 (57%) were returned with data suitable for statistical analysis. The median age of the cats with EPI was 7.7 years. The median body condition score was 3 of 9. Ninety-two of 119 cats (77%) had hypocobalaminemia, and 56 of 119 cats (47%) had increased and 6 of 119 cats (5%) had decreased serum folate concentrations. Clinical signs included weight loss (91%), unformed feces (62%), poor hair coat (50%), anorexia (45%), increased appetite (42%), lethargy (40%), watery diarrhea (28%), and vomiting (19%). Eighty-seven cats (58%) had concurrent diseases. Treatment response was reported to be good in 60%, partial in 27%, and poor in 13% of 121 cats. Trypsin-like immunoreactivity <4 µg/L was associated with a positive response to treatment (OR, 3.2; 95% CI, 1.5-7.0; P = .004). Also, cobalamin supplementation improved the response to treatment (OR, 3.0; 95% CI, 1.4-6.6; P = .006). CONCLUSIONS AND CLINICAL IMPORTANCE: Exocrine pancreatic insufficiency in cats often has a different clinical presentation than in dogs. The age range for EPI in cats is wide, and many cats can be ≤5 years of age. Most cats respond well to appropriate treatment for EPI, and cobalamin supplementation appears to be necessary for a good response.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.

[Fat-soluble vitamins supplementation in patients with cystic fibrosis: is enough Aquadek's®?]. / Suplementacion con vitaminas liposolubles en pacientes con fibrosis quistica: ¿es suficiente con Aquadek's®?

INTRODUCTION AND OBJECTIVE: Evaluate the safety and efficacy of a novel polyvitaminic (Aquadek's®) in patients with Cystic Fibrosis (CF). MATERIAL AND METHODS: Prospective, longitudinal and non-randomized study. CF patients with pancreatic insufficiency and clinically stable were given Aquadek's® (two chewable tablets) daily for 12 months. Serum levels of retinol, beta-carotene, 25 OH vitamin D and α-tocopherol were evaluated twelve months before, at baseline and 12 months after. STATISTICAL ANALYSIS: paired t tests. RESULTS: 28 patients aged 6 to 39 years (median 18.5 years) were included. Aquadek's® supplementation led to an increase in vitamin A dose and a decrease in the number of tablets administered. At baseline, 89% had at least one vitamin deficiency (61% pro-Vitamin A and 54% vitamin D). After one year, serum beta-carotene levels were increases 160 (95% CI 98-222) mcg/l (p <0.001) and decreased the percentage of patients with pro-vitamin A deficiency 46% (95% CI 22-64) (p <0.001). The proportion of patients with vitamin D insuficiency increased 18%(95% CI 2-32) (p =0.025). In any case serum levels exceeded the upper limits used to assess the risk of toxicity.Conclusions: Two daily Aquadek's® chewable tablets are safe and effective for maintaining vitamin A and E status of CF patients older than 6 years, although it is insufficient to normalize serum 25OHvitaminD according to the current recommendations for this disease.

Introducción y objetivo: Conocer si la suplementación un nuevo polivitamínico (Aquadek´s®) durante 12 meses es segura y eficaz en pacientes con Fibrosis Quística (FQ). Material y Métodos: Estudio prospectivo, longitudinal y no controlado en pacientes con FQ insuficientes pancreáticos, clínicamente estables, que recibieron suplementación con Aquadek´s® (2 comprimidos masticables) durante 12 meses en lugar de su suplementación habitual. Se evaluaron niveles séricos de retinol, betacarotenos, 25 OH vitamina D y α-tocoferol un año antes, al inicio y tras un año de tratamiento. Análisis estadístico: Pruebas t para datos pareados. Resultados: Se incluyeron 28 pacientes entre 6 y 39 años (mediana 18,5 años). La suplementación con Aquadek´s® supuso un incremento en la dosis de vitaminas A y una disminución del número de comprimidos administrados. Al inicio, un 89% presentaban algún tipo de déficit vitamínico: (61% pro-Vitamina A y 54% vitamina D). Tras un año, se produjo un incremento de los niveles de betacarotenos: 160 mcg/l (IC 95% 98-222) (p.

Pancreatic enzyme replacement therapy dosing and nutritional outcomes in children with cystic fibrosis.

OBJECTIVES: To utilize the Cystic Fibrosis Foundation Patient Registry to evaluate whether pancreatic enzyme dose is associated with better nutritional status as measured by average body mass index (BMI) percentile. STUDY DESIGN: A retrospective analysis of the Cystic Fibrosis Foundation Patient Registry from 2005-2008 was performed. The final analysis included 42 561 patient visits from 14 482 patients 2-20 years of age taking pancreatic enzyme replacement therapy from 179 programs. Cystic fibrosis care programs were assigned to quartiles based on adjusted mean patient BMI percentiles. Differences in median lipase dose between programs in the highest and lowest BMI quartiles were examined using a mixed effects model that adjusted for individual patient BMI, age, race, ethnicity, forced expiratory volume in 1 second percent, acid-blocker use, presence of Pseudomonas aeruginosa, nutritional supplement use, growth hormone use, and diagnosis of cystic fibrosis-related diabetes. RESULTS: A significant difference in median enzyme dose existed between the highest and lowest BMI quartiles. Multivariable analysis demonstrated the effect persisted after adjustment for covariates. Highest quartile programs had a median enzyme dose of 1755 lipase units/kg/meal compared with 1628 lipase units/kg/meal for lowest quartile programs. CONCLUSION: Patients attending US cystic fibrosis programs achieving highest nutritional outcomes, measured by mean BMI percentile, have higher enzyme dosing than those attending programs at lower performance levels. Further randomized clinical trials are necessary to determine the role of enzyme dose in improving nutritional outcomes.

Fat-soluble vitamins in cystic fibrosis and pancreatic insufficiency: efficacy of a nutrition intervention.

OBJECTIVES: The aim of the study was to assess the impact of LYM-X-SORB (LXS), an organized lipid matrix that has been shown to be absorbable without pancreatic enzyme therapy on fat-soluble vitamin status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI). METHODS: Children with CF and PI were randomized to daily LXS or an isocaloric placebo comparison supplement for 12 months. Serum vitamins A (retinol), D (25-hydroxyvitamin D[25D]), E (α-tocopherol, α-tocopherol:cholesterol ratio), and K (percentage of undercarboxylated osteocalcin [%ucOC] and plasma proteins induced by vitamin K absence factor II [PIVKA II]) were assessed at baseline and 12 months. Dietary intake was determined using 3-day weighed food records and supplemental vitamin intake by a comprehensive questionnaire. RESULTS: A total of 58 subjects (32 boys, age 10.3 ± 2.9 years [mean ± standard deviation]) with complete serum vitamin, dietary and supplemental vitamin data were analyzed. After adjusting for dietary and supplemental vitamin intake, serum retinol increased 3.0 ± 1.4 µg/dL (coefficient ± standard error) (adjusted R2 = 0.02, P = 0.03) and vitamin K status improved as demonstrated by a decreased percentage of undercarboxylated osteocalcin of -6.0% ± 1.6% by 12 months (adjusted R2 = 0.15, P < 0.001). These changes occurred in both the LXS and placebo comparison groups. No changes in serum 25D or α-tocopherol were detected. Both nutrition interventions increased caloric intake a mean of 83 ± 666 kcal/day by 12 months. CONCLUSIONS: Vitamins A and K status improved, whereas vitamins D and E status was unchanged during 12 months of LXS and isocaloric placebo comparison supplement in children with CF and PI.

Manual ventilation therapy and aggressive potassium supplementation in the management of respiratory failure secondary to severe hypokalaemia in a cat with exocrine pancreatic insufficiency.

A domestic shorthair cat was referred for progressive muscle weakness and dyspnoea. The cat had a 2-month history of severe weight loss, small intestinal diarrhoea, polyphagia and polyuria/polydipsia. Biochemical analysis and venous blood gas evaluation revealed severe hypokalaemia [1.7 mmol/l; reference interval (RI): 3.5-5.1 mmol/l] and hypoventilation (partial pressure of carbon dioxide = 68 mmHg; RI: 34-38 mmHg). Aggressive potassium supplementation was initiated. The cat was manually ventilated until serum potassium increased to 3 mmol/l. A diagnosis of exocrine pancreatic insufficiency (EPI) was made based on clinical signs and serum feline trypsin-like immunoreactivity (0.1 µg/l; RI: 12-82 µg/l). Medical management of the EPI resulted in clinical recovery.

Exocrine pancreatic insufficiency following esophagectomy.

Weight loss following esophagectomy is a management challenge for all patients. It is multifactorial with contributing factors including loss of gastric reservoir, rapid small bowel transit, malabsorption, and adjuvant chemotherapy. The development of a postoperative malabsorption syndrome, as a result of exocrine pancreatic insufficiency (EPI), is recognized in a subgroup of patients following gastrectomy. This has not previously been documented following esophageal resection. EPI can result in symptoms of flatulence, diarrhea, steatorrhea, vitamin deficiencies, and weight loss. It therefore has the potential to pose a significant level of morbidity in postoperative patients. There is some evidence that patients with proven EPI (fecal elastase-1 < 200 µg/g) may benefit from a trial of pancreatic enzyme replacement therapy (PERT). We observed symptoms compatible with EPI in a subgroup of patients following esophagectomy. We hypothesized that this was contributing to malabsorption and malnutrition in these patients. To investigate this, fecal elastase-1 was measured in postoperative patients, and in those with proven EPI, a trial of PERT was commenced in combination with specialist dietary education. At routine postoperative follow-up, which included assessment by a specialist dietitian, those patients with symptoms suggestive of malabsorption were given the opportunity to have their fecal elastase-1 measured. PERT was then offered to patients with fecal elastase-1 less than 200 µg/g (EPI) as well as those in the 200-500 µg/g range (mild EPI) with more severe symptoms. Fecal elastase-1 was measured in 63 patients between June 2009 and January 2011 at a median of 4 months (range 1-42) following surgery. Ten patients had fecal elastase-1 less than 200 µg/g, and all had failed to maintain preoperative weight. All accepted a trial of PERT. Nine (90%) had symptomatic improvement, and seven (70%) increased their weight. Thirty-nine patients had a fecal elastase-1 in the 200-500 µg/g range. Twelve were given a trial of PERT based on level of symptoms, five (42%) reported an improvement in symptoms, but only two (17%) gained weight. Our early results support the observation that EPI is a factor contributing to postoperative morbidity in patients recovering from esophagectomy and that these patients can benefit from a trial of PERT. Our study has limitations, and a formal trial is required to evaluate the impact of EPI and PERT following esophagectomy. Currently, our practice is to measure fecal elastase-1 in any patient with unexplained weight loss or symptoms of malabsorption. In patients with proven EPI or those who are symptomatic with mild EPI, a trial of PERT should be offered and symptoms reassessed.

Hyperammonaemia due to cobalamin malabsorption in a cat with exocrine pancreatic insufficiency.

A 10-year-old domestic shorthair cat showed anorexia, lethargy and ptyalism with hyperammonaemia. Portosystemic shunts were not identified by computed tomography angiography. Biopsy results revealed mild interstinal nephritis and no lesion in the liver. Analysis of urine revealed the presence of a high methylmalonic acid (MMA) concentration. Serum cobalamin (vitamin B(12)) and serum feline trypsin-like immunoreactivity levels were also markedly low. The cat was diagnosed as having exocrine pancreatic insufficiency (EPI). After 5 weeks of parenteral cobalamin supplementation, serum cobalamin concentration had increased and urinary MMA concentration had decreased. This case suggests that hyperammonaemia may be caused by accumulation of MMA due to cobalamin malabsorption secondary to feline EPI.

Vitamin D in children with cystic fibrosis.

PURPOSE: The Cystic Fibrosis Trust in 2007 published a recommended target of 75-150 nmol/L for 25-hydroxyvitamin D (25-OHD). In 2008 we found that only 10% of pancreatic insufficient (PI) children met this target. An increase in supplementation was implemented and a repeat audit performed in 2010. METHODS: PI children ≥1 year under sole-care in our regional centre were included. Vitamin D3 supplementation increased by >450% to either 3800 IU/day liquid or 800 IU daily plus 20,000 IU weekly tablets. In 2010 pancreatic sufficient (PS) children were also audited separately. RESULTS: The median 25-OHD level increased from 51.5 nmol/L in 2008 (n=78, 10% >75 nmol/L) to 72 nmol/L in 2010 (n=72, 51% >75 nmol/L), p<0.0001. In PS children (n=15 in 2010) 87% had 25-OHD levels <75 nmol/L. CONCLUSIONS: A substantial increase in supplementation led to a significant increase in 25-OHD levels but around half still failed to reach the recommended target.

Cinnamtannin B-1, a natural antioxidant that reduces the effects of H2O2 on CCK-8-evoked responses in mouse pancreatic acinar cells

This work was designed in order to gain an insight on the mechanisms by which antioxidants prevent pancreatic disorders. We have examined the properties of cinnamtannin B-1, which belongs to the class of polyphenols, against the effect of hydrogen peroxide (H2O2) in mouse pancreatic acinar cells. We have studied Ca2+ mobilization, oxidative state, amylase secretion, and cell viability of cells treated with cinnamtannin B-1 in the presence of various concentrations of H2O2. We found that H2O2 (0.1-100 ìM) increased CM-H2DCFDA-derived fluorescence, reflecting an increase in oxidation. Cinnamtannin B-1 (10 ìM) reduced H2O2-induced oxidation of CM-H2DCFDA. CCK-8 induced oxidation of CM-H2DCFDA in a similar way to low micromolar concentrations of H2O2, and cinnamtannin B-1 reduced the oxidant effect of CCK-8. In addition, H2O2 induced a slow and progressive increase in intracellular free Ca2+ concentration ([Ca2+]c). Cinnamtannin B-1 reduced the effect of H2O2 on [Ca2+]c, but only at the lower concentrations of the oxidant. H2O2 inhibited amylase secretion in response to cholecystokinin, and cinnamtannin B-1 reduced the inhibitory action of H2O2 on enzyme secretion. Finally, H2O2 reduced cell viability, and the antioxidant protected acinar cells against H2O2. In conclusion, the beneficial effects of cinnamtannin B-1 appear to be mediated by reducing the intracellular Ca2+ overload and intracellular accumulation of digestive enzymes evoked by ROS, which is a common pathological precursor that mediates pancreatitis. Our results support the beneficial effect of natural antioxidants in the therapy against oxidative stress-derived deleterious effects on cellular physiology (AU)

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.

Antibiotic therapy and fat digestion and absorption in cystic fibrosis.

Antibiotic therapy in the cystic fibrosis (CF) mouse model has been shown to result in reduced bacterial load of the intestine and significant body mass gain. The effect was suggested to be linked to the improvement of intestinal digestion and absorption. Therefore, we aimed to assess the influence of routinely applied antibiotic therapy in CF patients on fat assimilation. Twenty-four CF patients aged 6 to 30 years entered the study. Inclusion criteria comprised confirmed exocrine pancreatic insufficiency and bronchopulmonary exacerbation demanding antibiotic therapy. Exclusion criteria comprised: antibiotic therapy six weeks prior to the test, liver cirrhosis, diabetes mellitus, oxygen dependency, the use of systemic corticosteroids. In all enrolled CF subjects, (13)C-labelled mixed triglyceride breath test ((13)C MTG-BT) was performed to assess lipid digestion and absorption, before and after antibiotic therapy. Sixteen subjects were treated intravenously with ceftazidime and amikacin, eight patients orally with ciprofloxacin. Cumulative percentage dose recovery (CPDR) was considered to reflect digestion and absorption of lipids. The values are expressed as means (medians). The values of CPDR before and after antibiotic therapy did not differ in the whole studied group [4.6(3.3) % vs. 5.7(5.3) %, p = 0.100] as well as in the subgroup receiving them intravenously [4.6(3.2) % vs. 5.7(5.3) %, p = 0.327] or in that with oral drug administration [4.6(3.4) % vs. 5.7(5.4) %, p = 0.167]. In conclusion, antibiotic therapy applied routinely in the course of pulmonary exacerbation in CF patients does not seem to result in an improvement of fat digestion and absorption.

Manifestações gastrintestinais na fibrose cística / Gastrointestinal manifestations in cystic fibrosis

A mutação no gene que codifica a proteína reguladora da condutância transmembrana (CFTR) constitui-se na base das alterações encontradas na fibrose cística (FC), afetando também o sistema gastrintestinal, em especial o pâncreas e o fígado. Cerca de 90% dos pacientes com FC são insuficientes pancreáticos já no 1º ano, e os sinais clínicos são os associados à má-absorção intestinal de nutrientes e gorduras: esteatorreia, flatulência, distensão abdominal, desnutrição e deficiências de vitaminas lipossolúveis. A dosagem de elastase fecal destaca-se no diagnóstico da insuficiência pancreática, e tratamento baseia-se na reposição de enzimas pancreáticas. A dose é individualizada, inicialmente 500 a 1.000 U/kg de lipase nas refeições principais, não ultrapassando 2.500 U/kg/refeição ou 10.000 U/kg/dia, pelo risco de colonopatia fibrosante. A insuficiência pancreática também causa má-absorção de vitaminas lipossolúveis (vitaminas A, D, E, K), sendo necessária suplementação. A doença hepatobiliar costuma iniciar na primeira década de vida, e o critério diagnóstico baseia-se nos aspectos cliínicos, ecográficos e bioquímicos, que devem ser periodicamente revisados. O tratamento da hepatopatia associado à FC com o ácido ursodesoxicólico visa retardar a progressão da doença. No tratamento das complicações da hipertensão porta, como varizes esofágicas, utilizam-se a ligadura elástica e a escleroterapia por via endoscópica, a derivação porto-sistêmica e implantação de shunts intra-hepáticos. Nenhum tratamento previne a progressão de fibrose para cirrose multilobular, sendo o transplante hepático indicado nos casos de hipertensão portal grave e insuficiência hepática, nos pacientes que mantêm função pulmonar preservada.

The gene mutation that codifies the CFTR protein is responsible for the alterations seen in Cystic Fibrosis and affects the gastrointestinal system as well, specially pancreas and liver. Around 90% of the patients with CF are pancreatic insufficient already on their first year of life and the clinical signs are those associated with malabsorption of fat and nutrients presenting flatulence, abdominal distension, malnutrition, and deficiency of fat soluble vitamins. The dosage of pancreatic supplements is tailored to the individual needs, initially the dosage should be tried as 500 to 1000 U/kg of lipase for the main meals, never going above 2,500 U/kg/meal or 10,000U/kg/Day due to the risk of fibrosing colonopathy. The pancreatic insufficiency also causes malabsortion of fat soluble vitamins (A, D, E, K vitamins), so supplementation is necessary. The hepatobiliar disease usually starts on the first decade of life and the diagnostic criteria are based on clinical, ecographic and biochemical aspects that must be reviewed periodically. The treatment of CF-associated liver disease with ursodesoxicolic acid aims to slow down the progress of the disease. For the treatment of portal hypertension complications, such as oesophageal varicose veins, elastic bandages and endoscopic sclerotherapy, porto-systemic derivations and implantation of intra hepatic shunts are used. No treatment is able to prevent the progress from fibrosis to multilobular cirrhosis, so in case of severe portal hypertension and hepatic insufficiency, the liver transplant is recommended, in patients who maintain their pulmonary functions preserved.

Digestive and nutritional considerations in celiac disease: could supplementation help?

Due to the increased immune activation in the intestinal tract of people with celiac disease, the digestive and absorptive processes of those affected may be compromised. Individuals with celiac disease are more susceptible to pancreatic insufficiencies, dysbiosis, lactase insufficiencies, and folic acid, vitamin B12, iron, and vitamin D deficiencies, as well as accelerated bone loss due to an increase in inflammatory signaling molecules. Beyond strict maintenance of a gluten-free diet, research has shown benefit with additional nutritional supplementation to assist in regulation of several of these complications.