Nano spirulina dietary supplementation augments growth, antioxidative and immunological reactions, digestion, and protection of Nile tilapia, Oreochromis niloticus, against Aeromonas veronii and some physical stressors.

The current study evaluated the effects of nano delivery of Spirulina platensis on growth performance, digestive enzymes, and biochemical, immunological, and antioxidative status, as well as resistance to Aeromonas veronii and some physical stressor challenges in Nile tilapia, Oreochromis niloticus. Three experimental fish groups (n = 270) with mean weights of 26 ± 0.30 g and mean lengths of 10 ± 0.5 cm were used; the first additive-free basal diet served as the control group, whereas the following two groups were supplemented with spirulina nanoparticles (SPNP) at 0 (control), 0.25, and 0.5%/kg diet for 4 weeks. Following the feeding trial, fish were challenged with hypoxia, cold stresses, and pathogenic bacteria (A. veronii) infection (9 × 108 CFU/ml). SPNP supplementation, especially 0.5%, (p < 0.05) significantly increased growth performance (specific growth rate % day-1, feed conversion ratio, and length gain rate %), immunological (plasma lysozyme and liver nitrous oxide) antioxidants (superoxide dismutase, catalase, and glutathione peroxidase in liver), biochemical (aspartate aminotransferase, alanine transaminase, glucose, and cortisol concentrations in plasma) assays, and digestive enzymes (lipase and amylase in plasma). The expression of liver's heat shock protein 70 (HSP70) and interleukin 1, beta (IL-1ß) genes showed a significant upregulation outline of 0.5% SPNP > 0.25% SPNP > 0% SPNP compared with the control. Protection in the incorporated fish groups exposed to A. veronii was 100% compared with the control group, which showed 50% cumulative mortalities. In conclusion, dietary SPNP supplementation improved growth performance, antioxidant activity, immune response, digestive enzymes, related gene expression, and resistance of Nile Tilapia to hypoxia, cold, and A. veronii infection. Thus, SPNP could be used as a natural therapy for controlling those stressors.

Shenmai Injection Upregulates Heme Oxygenase-1 to Confer Protection Against Severe Acute Pancreatitis.

BACKGROUND: To explore the mechanism of Shenmai injection (SMI) on severe acute pancreatitis (SAP) through heme oxygenase-1 (HO-1) signaling. METHODS: A total of 40 male Sprague-Dawley (SD) rats (220-260 g) were grouped into the following four categories (n = 10): SAP + SMI + Zinc protoporphyrin (ZnPP), SAP + SMI, SAP, and sham surgery groups. ZnPP is a specific inhibitor of HO-1. Four percent of sodium taurocholate (1 mL/kg) was retrogradely injected via the pancreatic duct to induce the SAP model. The SAP group rats received 1.6 mL/kg saline by intravenous injection 30 min after the induction of SAP. The SAP + SMI group rats received 1.6 mL/kg SMI by intravenous injection 30 min after the induction of SAP. The SAP + SMI + ZnPP group rats received an intravenous injection of 1.6 mL/kg SMI and intraperitoneal administration of 30 mg/kg ZnPP 30 min after the SAP induction. Twenty-four hours after the SAP induction, blood samples were collected for the measurement of amylase, lipase, creatinine, myeloperoxidase, interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and HO-1 level, while tissue specimens were harvested for the determination of HO-1, TNF-α, and IL-10 mRNA level. Meanwhile, histopathological changes in organs (pancreas, lung, and kidney) were stored. RESULTS: The serum concentration of amylase, lipase, creatinine, and myeloperoxidase was higher in the SAP group than in the SAP + SMI group. Treatment with SMI increased HO-1 and IL-10 level and reduced TNF-α level in serum and tissues compared to the SAP group (P < 0.05). Treatment with SMI abolished the organ-damaging effects of SAP (P < 0.05). Furthermore, suppression of HO-1 expression by ZnPP canceled the aforementioned effects. CONCLUSIONS: SMI confers protection against the SAP-induced systemic inflammatory response and multiple organs damage via HO-1 upregulation.

Cholecystokinin Receptor Antagonist Therapy Decreases Inflammation and Fibrosis in Chronic Pancreatitis.

BACKGROUND AND AIMS: Chronic pancreatitis is associated with recurrent inflammation, pain, fibrosis, and loss of exocrine and endocrine pancreatic function and risk of cancer. We hypothesized that activation of the CCK receptor contributes to pancreatitis and blockade of this pathway would improve chronic pancreatitis. METHODS: Two murine models were used to determine whether CCK receptor blockade with proglumide could prevent and reverse histologic and biochemical features of chronic pancreatitis: the 6-week repetitive chronic cerulein injection model and the modified 75% choline-deficient ethionine (CDE) diet. In the CDE-fed model, half the mice received water supplemented with proglumide, for 18 weeks. After chronic pancreatitis was established in the cerulein model, half the mice were treated with proglumide and half with water. Histology was scored in a blinded fashion for inflammation, fibrosis and acinar ductal metaplasia (ADM) and serum lipase levels were measured. RNA was extracted and examined for differentially expressed fibrosis genes. RESULTS: Proglumide therapy decreased pancreatic weight in the CDE diet study and the cerulein-induced chronic pancreatitis model. Fibrosis, inflammation, and ADM scores were significantly reduced in both models. Lipase values improved with proglumide but not in controls in both models. Proglumide decreased pancreas mRNA expression of amylase, collagen-4, and TGFßR2 gene expression by 44, 38, and 25%, respectively, compared to control mice. CONCLUSION: New strategies are needed to decreased inflammation and reduce fibrosis in chronic pancreatitis. CCK receptor antagonist therapy may improve chronic pancreatitis by reversing fibrosis and inflammation. The decrease in ADM may reduce the risk of the development of pancreatic cancer.

The Effects of Lycium Barbarum Polysaccharide (LBP) in a Mouse Model of Cerulein-Induced Acute Pancreatitis.

BACKGROUND Acute pancreatitis is an inflammatory disease of the pancreas associated with high patient morbidity. Lycium barbarum polysaccharide (LBP), a traditional Chinese medicine with an active component extracted from the goji berry, has previously been reported to have anti-inflammatory effects. This study aimed to investigate the effects of LBP in a mouse model of cerulein-induced acute pancreatitis. MATERIAL AND METHODS Acute pancreatitis was induced by intraperitoneal injection of cerulein in C57BL/6 wild-type mice or nuclear factor erythroid-2-related factor 2 (NRF2) gene knockout mice. LBP or normal saline was administrated by gavage once daily for one week before the induction of acute pancreatitis. At 12 hours after the first intraperitoneal injection of cerulein, the mice were euthanized. Blood and pancreatic tissue were sampled for histology and for the measurement of pro-inflammatory cytokines, serum amylase, and lipase. RESULTS In the untreated mouse model of cerulein-induced acute pancreatitis, amylase and lipase levels were increased, and these levels were reduced by LBP treatment when compared with vehicle treatment. In the untreated mouse model, histology of the pancreas showed edema and inflammation, which were reduced in the LBP-treated mice. In the untreated mouse model, increased levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were found, which were reduced in the LBP-treated mice. NRF2 gene knockout mice with cerulein-induced acute pancreatitis showed reduced anti-inflammatory effects of LBP treatment. LBP increased the expression of NRF2 and heme oxygenase-1 (HO-1). CONCLUSIONS In a mouse model of cerulein-induced acute pancreatitis, LBP reduced inflammation by upregulating NRF2 and HO-1.

Visnagin attenuates acute pancreatitis via Nrf2/NFκB pathway and abrogates associated multiple organ dysfunction.

Acute pancreatitis (AP) is an exocrine dysfunction of the pancreas where oxidative stress and inflammatory cytokines play a key role in induction and progression of the disease. Studies have demonstrated that antioxidant phytochemicals have been effective in improving pancreatitis condition, but there are no clinically approved drugs till date. Our study aims to assess the preventive activity of visnagin, a novel phytochemical isolated from Ammi visnaga against cerulein induced AP. Male Swiss albino mice were divided into six groups (n = 6, each group) comprising of normal control, cerulein control, seven day pre-treatment with visnagin at three dose levels; visnagin low dose (10 mg/kg), visnagin mid dose (30 mg/kg), visnagin high dose (60 mg/kg) and visnagin control (60 mg/kg). AP was induced by six injections of cerulein (50 µg/kg, i.p.) on the 7th day and the animals were sacrificed after 6 h of last cerulein dose. Various markers of pancreatic function, oxidative stress and inflammation were assessed. Visnagin was found to be effective in reducing plasma amylase and lipase levels, reduced cerulein induced oxidative stress. Visnagin dose dependently decreased the expression of IL-1ß, IL-6, TNF-α and IL-17. It attenuated the levels of nuclear p65-NFκB. Visnagin improved the antioxidant defence by improving Nrf2 expression and halted pancreatic inflammation by suppressing NFκB and nitrotyrosine expression in the acinar cells. Further, it attenuated the expression of markers of multiple organ dysfunction syndrome and reduced inflammatory cytokines in lungs and intestine. Cumulatively, these findings indicate that visnagin has substantial potential to prevent cerulein induced AP.

Taxifolin prevents postprandial hyperglycemia by regulating the activity of α-amylase: Evidence from an in vivo and in silico studies.

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.

Pharmacokinetics of glycerol phenylbutyrate in pediatric patients 2 months to 2 years of age with urea cycle disorders.

INTRODUCTION: Glycerol phenylbutyrate (GPB) is approved in the US and EU for the chronic management of patients ≥2 months of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. GPB is a pre-prodrug, hydrolyzed by lipases to phenylbutyric acid (PBA) that upon absorption is beta-oxidized to the active nitrogen scavenger phenylacetic acid (PAA), which is conjugated to glutamine (PAGN) and excreted as urinary PAGN (UPAGN). Pharmacokinetics (PK) of GPB were examined to see if hydrolysis is impaired in very young patients who may lack lipase activity. METHODS: Patients 2 months to <2 years of age with UCDs from two open label studies (n = 17, median age 10 months) predominantly on stable doses of nitrogen scavengers (n = 14) were switched to GPB. Primary assessments included traditional plasma PK analyses of PBA, PAA, and PAGN, using noncompartmental methods with WinNonlin™. UPAGN was collected periodically throughout the study up to 12 months. RESULTS: PBA, PAA and PAGN rapidly appeared in plasma after GPB dosing, demonstrating evidence of GPB cleavage with subsequent PBA absorption. Median concentrations of PBA, PAA and PAGN did not increase over time and were similar to or lower than the values observed in older UCD patients. The median PAA/PAGN ratio was well below one over time, demonstrating that conjugation of PAA with glutamine to form PAGN did not reach saturation. Covariate analyses indicated that age did not influence the PK parameters, with body surface area (BSA) being the most significant covariate, reinforcing current BSA based dosing recommendations as seen in older patients. CONCLUSION: These observations demonstrate that UCD patients aged 2 months to <2 years have sufficient lipase activity to adequately convert the pre-prodrug GPB to PBA. PBA is then converted to its active moiety (PAA) providing successful nitrogen scavenging even in very young children.

Comparative study of three predominant gut Bacillus strains and a commercial B. amyloliquefaciens as probiotics on the performance of Clarias gariepinus.

The present study was conducted to evaluate the supplementation of three autochthonous Bacillus strains (B. subtilis, B. amyloliquefaciens and B. cereus) and a commercial B. amyloliquefaciensin doses of 1 × 1010 CFU/kg on the growth performance, hematology, antioxidant activities, digestive enzyme levels, immune status and disease resistance of Clarias gariepinus. A total of 300 fish (75.23 ±â€¯1.6 g) were randomly divided into 5 groups (each group was subdivided into 2 subgroups, 30 fish/each). The control group was fed basal diet (D0). Diets D1, D2, D3 and D4were supplemented with B. subtilis, B. amyloliquefaciens, B. cereus and a commercial B. amyloliquefaciens, respectively. During the course of the experiment, D3 showed the best body weight, weight gain, specific growth rate and food conversion ratio. The measured hemogram blood parameters had the highest significant increase in D3. WBCs and monocyte counts had no significant differences among the experimental groups. The serum antioxidant and digestive enzymes were the highest in D3 and were the lowest in D0. After 15 d, the non-specific immune parameters were markedly increased in fish fed probiotic-containing diet compared with the control. After 30 d, the highest significant immune parameters were observed in D3; D1 and D2 had no significant differences in serum lysozyme activity, nitric oxide and IgM compared with D0. Myostatin cDNA levels were adversely affected by probiotic supplements compare with the control. The PACAP expression showed the highest significant value in D3 followed by D1and D4then D2. The relative survival percentages of the Aeromonas sobria challenged C. gariepinus were the highest in D3, D2, D4 and then D1. Among the three isolated Bacillus species, dietary supplementation with the B. cereus had the highest performance in C. gariepinus compared with the commercial B. amyloliquefaciens and the control group.

Anti-Obesity Effect of Arq Zeera and Its Main Components Thymol and Cuminaldehyde in High Fat Diet Induced Obese Rats.

Arq zeera is a distillate product that prepared from four different herbs namely Trachyspermum ammi L., apiaceae, Zingiber officinale Roxb., zingiberaceae, Carum carvi L.,apiaceae and Cuminum cyminum L., apiaceae. The present study aims to determine the antiobesity effect of arq zeera and its main components thymol and cuminaldehyde in high fat diet induced obese rats and to explore its mechanism of action. In current study, orlistat was used as positive controls. Male Wistar rats were fed with HFD for 42 days to induce obesity. HFD-fed rats were administered with arq zeera, thymol, cumic aldehyde, thymol + cuminaldehyde and orlistat for 28 days. During the course of treatment, body weight and food intake frequently observed and after end of treatments, liver weight, visceral fat pad weight, plasma lipid proflie, alanine aminotransferase, aspartate aminotransferase, glucose, insulin, leptin levels and pancreatic lipase activity were studied on all treated obese rats. The histopathology of liver was also studied. After the treatments of arq zeera and its main components, body weight, food intake, liver weight, visceral fat pad weight and the level of lipid profile, alanine aminotransferase, aspartate aminotranferase, glucose, insulin, and leptin were found to be decreased and pancreatic lipase inhibition were increased. Arq zeera showed more potential antiobesity effect than orlistat. According to our present findings, arq zeera and its main components possessed potent antiobesity effect on high fat diet -induced obese rats and excreted anti-obesity effect partly via hypolipidemic, hypoglycemic, hypoinsulinemic, hypoleptinemic and pancreatic lipase inhibition action.

Effects of Berberine on Acute Necrotizing Pancreatitis and Associated Lung Injury.

OBJECTIVES: We set out to examine whether berberine (BBR) might affect the severity of pancreatitis and pancreatitis-associated lung injury in choline-deficient ethionine-supplemented (CDE) diet-induced severe acute pancreatitis. METHODS: Severe acute pancreatitis was induced by feeding a CDE diet for 3 days. Berberine was administered intraperitoneally during CDE diet. Mice were killed on days 1, 2, and 3 after the onset of CDE diet. The severity of pancreatitis was assessed by evaluating changes to the pancreas and lung and survival rate. Blood, pancreas, and lung were harvested for further examination. Furthermore, the regulating mechanisms of BBR were evaluated on the pancreas. RESULTS: Administration of BBR significantly inhibited histological damage to the pancreas and lung and decreased serum level of amylase and lipase, myeloperoxidase activity, cytokine production, and the mortality rate. Furthermore, administration of BBR inhibited activation of nuclear factor kappa B, c-Jun N-terminal kinases, and p38 in the pancreas during CDE diet. CONCLUSIONS: These findings suggest that BBR attenuates the severity of pancreatitis by inhibiting activation of nuclear factor kappa B, c-Jun N-terminal kinase, and p38 and that BBR could be used as a beneficial agent to regulate AP.

Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury.

AIM: To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction (SJD) in rats with acute pancreatitis (AP) for protecting against multiple organ injury. METHODS: An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group (CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD (CG + SJD) and a model group treated with SJD (MG + SJD), both of which were orally administered with SJD (5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male Sprague-Dawley rats were randomly divided into a CG, an AP model group (MG), and an SJD treated AP group (SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination. RESULTS: The MG + SJD displayed significantly shorter mean residence time (MRT) and higher clearance (CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve (AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α levels in the MG were higher than those in the CG (P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG (P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG (P < 0.05). CONCLUSION: AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro- and anti- inflammatory responses, which might guide the clinical application of SJD for AP treatment.

Low-methoxyl lemon pectin attenuates inflammatory responses and improves intestinal barrier integrity in caerulein-induced experimental acute pancreatitis.

SCOPE: Acute pancreatitis (AP) is a common clinical acute abdominal disease. The intestinal injury associated with AP will aggravate the condition retroactively. This study investigates whether the low-methoxyl pectin (LMP) isolated from lemon could attenuate AP and associated intestinal injury. METHODS AND RESULTS: Experimental AP was induced in BALB/c mice by caerulien (CAE) hyperstimulation. Nutritional prophylactic group was pre-fed with 5% LMP supplemented forage 3 days before AP induction. We found that LMP supplementation attenuated the severity of AP as evidenced by reduced serum amylase and lipase levels, pancreatic edema and myeloperoxidase activity. The protective effect was also confirmed by histological examination of pancreatic damage. LMP suppressed the production of pancreatic proinflammatory cytokines including TNF-α, IL-1ß, and IL-6. Moreover, LMP supplementation restored AP-associated disruption of intestinal barrier integrity as evidenced by upregulation of tight junction modulatory proteins occludin, zonula occludens (ZO)-1, antimicrobial peptides ß-defensin-1 (DEFB1) and CRAMP as well as increase in SCFAs production. LMP supplemented mice with AP exhibited suppressed intestinal inflammation as shown by decreased ileal and colon cytokine production compared with CAE group. CONCLUSION: Our results support dietary LMP supplementation as an effective nutritional intervention for AP and associated intestinal injury.

Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary Pancreatitis in An Experimental Rat Model.

Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. MATERIALS AND METHODS: Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. RESULTS: Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. CONCLUSIONS: These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.

The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disease that has an increasing incidence worldwide. AP is associated with high morbidity and mortality rates ranging 15-40% in its severe form. Oxidative stress plays an important role in pancreatic acinar cell injury in case of AP. Melatonin (Mel) is proven to have both antioxidant and anti-inflammatory effects. The aim of the work was to investigate the protective role of Mel against L-arginine (L-arg)-induced AP in adult male albino rats. MATERIALS AND METHODS: Thirty-six adult male albino rats were used in this study. Animals were divided into four groups; Control group (Group A; n = 6), Mel group (Group B; n = 6), L-arg group (Group C; n = 12) receiving two doses of L-arg injection with 1 h interval in-between, and L-arg+Mel group (Group D; n = 12) receiving Mel 1 h after each L-arg injection. 24 h after the second L-arg injection, the serum levels of amylase (AM), lipase (LP), interleukin-6 (IL-6) and tumour necrotic factor-alpha (TNF-α) were determined. Then, pancreatic specimens were processed for histological and immunohistochemical staining with vascular endothelial growth factor (VEGF) and the area percentage of VEGF and collagen content were measured by digital image analysis. RESULTS: Microscopic examination revealed that animals received L-arg only (Group C) showed loss of the pancreatic lobular architecture with marked fibrosis, acinar degeneration, inflammatory reaction and marked oedema with vascular congestion. Also, L-arg-induced AP caused a significant elevation of the serum levels of AM, LP, IL-6. All these histo-pathological and serological parameters were markedly improved by Mel administration. CONCLUSIONS: Melatonin exhibits strong therapeutic effects in the course of AP. Hence, the use of Mel as adjuvant treatment in AP is recommended.

Pancreatic functions in adolescents with beta thalassemia major could predict cardiac and hepatic iron loading: relation to T2-star (T2*) magnetic resonance imaging.

The aim of this study is to assess the correlation between cardiac and hepatic T2* MRI findings with the endocrine and exocrine pancreatic functions in known patients with ß-thalassaemia major (ß-TM). A total of 50 adolescent patients with ß-TM and 44 healthy controls were investigated via: serum amylase, lipase, triglyceride index, oral glucose tolerance test and T2* MRI, to assess iron content in the heart and liver. Diabetes was found in 20%, and 40% of patients had impaired fasting glucose (IFG). Cardiac T2* was less than 10 ms in 22% indicating heavy load with iron in cardiac tissues. There was a significant decrease in median serum amylase (63.5 vs 87.5 IU/L, p=0.003) and lipase (63 vs 90 IU/L, p=0.017) among patients in comparison with the control group. Patients with ß-TM and diabetes had lower serum amylase (32 vs 68 IU/L), lipase (28 vs 79 IU/L), cardiac and hepatic T2* MRI (7 vs 25.5 ms; 3 vs 6 ms, p<0.001 for all) than those without diabetes. Similar results were found among patients with IFG when compared with others (p<0.001 for all). Cardiac and hepatic T2* were inversely correlated to triglyceride index (r=-0.376, p=0.014 and r=-0.475, p=0.001, respectively) and positively correlated to amylase (r=0.791 and r=0.790) and lipase (r=0.784 and r=0.783; p<0.001 for all). The endocrine and exocrine pancreatic functions might become an equivalent predictor to cardiac and hepatic iron overload, especially in countries where MRI is not available or where it is expensive. The early occurrence of these abnormalities warrants more intensive chelation therapy.

Growth, immune, antioxidant, and bone responses of heat stress-exposed broilers fed diets supplemented with tomato pomace.

A study was conducted to investigate the effects of supplementation of dried tomato pomace (DTP) on growth performance, relative weights of viscera, serum biological parameters, antioxidant status, immune response, and bone composition of broilers exposed to a high ambient temperature. A total of 352 one-day-old male broiler chickens were randomly divided into four groups consisting of four replicates with 22 birds each. One group was reared under the thermoneutral zone and fed a corn-soybean meal basal diet. The other three groups were subjected to a cyclic heat stress from 29 to 42 days of age (34 ± 1 °C, 55 % RH, 5 h/day). These birds were fed corn-soybean meal basal diet or the same diet supplemented with 3 % DTP (420 mg lycopene/kg diet) or 5 % (708 mg lycopene/kg diet) of DTP. Blood samples were collected on days 28 and 42, and the birds were slaughtered at the same times. Supplementation of 5 % of DTP increased body weight and production index and decreased feed conversion ratio during 1-28 days of age. On day 28, the broilers supplemented with 5 % DTP had lower serum triglycerides and higher high-density lipoprotein (HDL) cholesterol concentration than those on the other dietary treatments. The activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were higher and the concentration of malondialdehyde (MDA) was lower in the broilers fed 5 % TP than those of the broilers fed other diets at 28 days of age. The effects of heat stress (HS) were impaired body weight, enhanced serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lipase, and MDA concentration while reducing the activities of GPx and SOD. Dried tomato pomace supplementation did not influence growth performance under HS but ameliorated the negative effects of HS on the serum enzyme activities, GPx activity, and lipid peroxidation. Heat stress did not change the relative weights of the lymphoid organs but reduced the total and IgG titers for secondary antibody response to sheep red blood cells and titer against Newcastle disease virus and increased the heterophil/lymphocyte ratio. The supplementation with 5 % of DTP completely alleviated the negative effects of HS on immune responses. The ash, Ca, and P contents of the tibia bone were decreased under HS. The ash and Ca contents of the tibia were not significantly different between thermoneutral and heat-stressed broilers supplemented with 5 % DTP. In conclusion, dietary supplementation of DTP, particularly 5 % DTP, to broiler diet attenuated the detrimental effects of HS on the activities of serum enzymes, oxidative status, immune response, and bone composition.

Assessment of prophylactic effect of Senna auriculata (L.) Roxb. leaves on alcohol-induced pancreatitis in rat model.

Aqueous leaf extract of Senna auriculata (L.) Roxb. syn. Cassia auriculata (SLEx) is known to possess potential antidiabetic and antioxidant properties. Based on the known correlation between exocrine pancreatic function and endocrine secretary capacity, here, we studied the prophylactic effect of the SLEx on alcohol induced pancreatitis in rats. To induce chronic pancreatitis, the rats were fed with unsaturated fat i.e. corn oil (2.5 mL/kg) along with high dose of ethanol (10.2 g/kg) for 4 wk, and was increased 0.6 g/kg after every 2 days for 1 wk and then 0.6 g/kg after every 4 days for a period of 4 wk. SLEx was orally administered to rats at dose of 400 mg/kg/day for 4 wk. At the end of 4th wk, pancreatic enzymes i.e., α-amylase, lipase, serum and pancreatic MDA levels were estimated. Pancreatic histopathological studies were also performed. The SLEx significantly reduced the serum levels of α-amylase and lipase along with significant suppression in serum and pancreatic tissue lipid peroxidation. Histomorphological studies did not show any fatty vacoules in acinar cells of SLEx-treated rats. However, vacoulation was seen in acini of pathogenic control rats. With the results, we conclude that Senna auriculata aqueous leaf extract has potential to reduce the ethanol-induced pathogenecity, and it possesses prophylactic effect on alcohol-induced pancreatitis. However, a long term trial is needed to ascertain its therapeutic potential for pancreatitis.

Retinoic Acid Ameliorates Pancreatic Fibrosis and Inhibits the Activation of Pancreatic Stellate Cells in Mice with Experimental Chronic Pancreatitis via Suppressing the Wnt/ß-Catenin Signaling Pathway.

Pancreatic fibrosis, a prominent feature of chronic pancreatitis (CP), induces persistent and permanent damage in the pancreas. Pancreatic stellate cells (PSCs) provide a major source of extracellular matrix (ECM) deposition during pancreatic injury, and persistent activation of PSCs plays a vital role in the progression of pancreatic fibrosis. Retinoic acid (RA), a retinoid, has a broad range of biological functions, including regulation of cell differentiation and proliferation, attenuating progressive fibrosis of multiple organs. In the present study, we investigated the effects of RA on fibrosis in experimental CP and cultured PSCs. CP was induced in mice by repetitive cerulein injection in vivo, and mouse PSCs were isolated and activated in vitro. Suppression of pancreatic fibrosis upon administration of RA was confirmed based on reduction of histological damage, α-smooth muscle actin (α-SMA) expression and mRNA levels of ß-catenin, platelet-derived growth factor (PDGF)-Rß transforming growth factor (TGF)-ßRII and collagen 1α1 in vivo. Wnt 2 and ß-catenin protein levels were markedly down-regulated, while Axin 2 expression level was up-regulated in the presence of RA, both in vivo and in vitro. Nuclear translation of ß-catenin was significantly decreased following RA treatment, compared with cerulein-induced CP in mice and activated PSCs. Furthermore, RA induced significant PSC apoptosis, inhibited proliferation, suppressed TCF/LEF-dependent transcriptional activity and ECM production of PSC via down-regulation of TGFßRII, PDGFRß and collagen 1α1 in vitro. These results indicate a critical role of the Wnt/ß-catenin signaling pathway in RA-induced effects on CP and PSC regulation and support the potential of RA as a suppressor of pancreatic fibrosis in mice.

Dachengqi Decoction Attenuates Inflammatory Response via Inhibiting HMGB1 Mediated NF-κB and P38 MAPK Signaling Pathways in Severe Acute Pancreatitis.

BACKGROUND/AIMS: Severe acute pancreatitis (SAP) is a sudden inflammation of the pancreas. The traditional Chinese medicine formula Dachengqi decoction (DCQD) is proven to be beneficial in the comprehensive treatment for pancreatitis patients in clinical practice. However, the molecular mechanism of DCQD on SAP remains unclear. High mobility group box 1(HMGB1) that functions as a damage-associated molecular pattern molecule (DAMP) has attracted much interest. METHODS: In this study, we used lipopolysaccharide (LPS) and cerulein to induce severe acute pancreatitis in C57BL/6 mice with subsequent administration with low, medium and high dose (2.3 g/kg, 7 g/kg and 21 g/kg, respectively) of DCQD. RESULTS: DCQD treatment improved the pathological score and decreased serum amylase and lipase in a dose-dependent manner. In addition, it suppressed the immune cell-induced secretion of HMGB1 and its translocation from the nucleus to the cytoplasm, thus repressing the expression of IL-6 and TNF-α. Further, pretreatment with DCQD decreased responses of TLRs, and suppressed the activation of NF-κB and p38 MAPK pathway. CONCLUSION: Decreasing the secretion of HMGB1 could reduce pro-inflammatory cytokines, which may help cutting down the risks of development from localized pathological changes to a systemic inflammatory response syndrome and even lead to multiple organ failure.