Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced chronic injury in rats

Abstract

Context: Bovine pancreatic trypsin inhibitor (BPTI) has been reported to relieve liver ischemia-reperfusion-induced injury in rats.

Objective: This study was designed to determine whether the recombinant BPTI (rBPTI) can prevent the chronic liver injury induced by CCl₄ in rats.

Materials and methods: Fifty male Wistar rats were divided into five groups. Rats were treated with 40% CCl₄ at a dose of 2?ml/kg body weight twice a week subcutaneously for 12 weeks. In the 8th week, they were administered intraperitoneally with rBPTI (80 MU/kg), BPTI (80 MU/kg) or hepatocyte growth-promoting factor (pHGF; 100?mg/kg) daily for the next 4 weeks.

Results: rBPTI significantly prevented the disruption of liver function of alanine aminotransferase (ALT; 172.7?±?18.16 versus 141.2?±?15.28, p?=?0.003), aspartate aminotransferase (AST; 225.10?±?36.54 versus 170.06?±?27.14, p?=?0.007) and hydroxyproline (Hyp; 1.14?±?0.27 versus 0.62?±?0.17, p?=?0.001). rBPTI significantly decreased the level of thiobarbituric acid reactive substances (TBARS; 1.15?±?0.16 versus 0.87?±?0.15, p?=?0.003) and increased the activities of superoxide dismutase (SOD; 6.07?±?0.95 versus 7.75?±?1.12, p?=?0.007). rBPTI reduced the production of cytokines of IL-1β and TGF-β. The hepatocyte necrosis, fibrosis, fatty degeneration and inflammatory cell infiltration were ameliorated by rBPTI administration.

Conclusion: This study demonstrated that rBPTI exerted a hepatoprotective effect on chronic liver fibrosis induced by CCl₄, which suggests that rBPTI may have the potential application for chronic liver injury induced by drugs metabolism and toxic substances.     

Sulfur mustard exposure and mental health in survivors of Iran–Iraq war with severe lung injuries

To evaluate mental health status of the survivors with sulfur mustard (SM) induced severe lung injury (n?=?291), Iranian standardized symptom checklist 90-revised (SCL90-R) questionnaire was used. The global severity index (GSI) was compared with the cutoff point of Iranian general population (0.4). About (32.9%, n?=?96) had a positive history of previous psychiatric problems. Additional war-related injuries was observed in (89.4%, n?=?261). The mean GSI (1.74?±?0.74) significantly was higher compared to standardized Iranian cutoff point (p?p?相似文献   

Effectiveness of heparin eye drops in paraquat-induced ocular injury

Purpose: To evaluate the efficacy of heparin eye drops in the treatment of paraquat-induced ocular surface injury.

Design and methods: In this retrospective study, we included 25 patients (31 eyes) with paraquat-induced ocular surface injury, who attended the Affiliated Hospital of Weifang Medical University between October 2008 and October 2013. The patients were split into two groups according to whether or not received heparin eye drops. The clinical data were compared between the two groups, i.e. clinical histories, results of examinations, treatments and outcomes.

Results: Eleven patients (group A, 15 eyes) received prompt irrigation with 0.9% saline every two hours, 0.1% pranoprofen eye drops four times a day, 20% autologous serum every two hours, recombinant bovine basic fibroblast growth factor eye-gel two times a day, oral vitamin C 2.0?g and prednisone 30?mg daily. Fourteen patients (group B, 16 eyes) received additional treatment with heparin eye drops. Ten eyes in group A and seven eyes in group B developed a pseudomembrane on the ocular surface at significantly different rate (mean?±?SD) of 1.20?±?1.01 and 0.43?±?0.51, respectively (t?=?2.66, p?=?0.01). Seven eyes among 10 had a pseudomembrane reoccurred in group A while none had a pseudomembrane reoccurred in group B (Fisher’s exact test, p?=?0.01). No significant differences were seen in the duration of epithelial recovery between the two groups: 15.13?±?5.13 days in group A and 16.81?±?5.56 days in group B (t?=?0.87, p?=?0.39). After the treatment, mild corneal opacity and pannus were observed in five patients of group A and four patients of group B, without any significant difference between the two groups (p?=?0.70).

Conclusions: The paraquat-induced ocular surface injury observed in this case series was characterized by the formation of conjunctival pseudomembrane with good prognosis and mild complications. Heparin eye drops reduce the occurrence, especially the reoccurrence of pseudomembrane. Further studies are warranted.     

Effects of exenatide versus sitagliptin on postprandial glucose,insulin and glucagon secretion,gastric emptying,and caloric intake: a randomized,cross-over study

ABSTRACT

Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients.

Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33?±?5?kg/m²; HbA_1c: 8.5?±?1.2%; 2-h PPG: 245?±?65?mg/dL. Patients received exenatide (5?µg BID for 1 week, then 10?µg BID for 1 week) or sitagliptin (100?mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581).

Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133?±?6?mg/dL versus 208?±?6?mg/dL, p?<?0.0001 (evaluable, N?=?61). Switching from exenatide to sitagliptin increased 2-h PPG by +73?±?11?mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by ?76?±?10?mg/dL. Postprandial glucose parameters (AUC, C_ave, C_max) were lower with exenatide than sitagliptin (p?<?0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (?15?±?4?mg/dL vs. ?19?±?4?mg/dL, p?=?0.3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50?±?0.26, p?=?0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88?±?0.03, p?=?0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90?±?0.04, p?=?0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56?±?0.05, p?<?0.0001). Exenatide reduced total caloric intake compared to sitagliptin (?134?±?97?kcal vs. +130?±?97?kcal, p?=?0.0227, N?=?25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature.

Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.     

Effects of calcitriol on bone mineral density in patients treated with esomeprazole

Context: Proton pump inhibitor (PPI) increases the risk of decrease in bone mineral density (BMD). However, whether calcitrol improves this situation is unknown.

Objective: The current study investigates the effects of calcitriol on BMD in patients with esomeprazole therapy.

Materials and methods: Three hundred and eighty-six participants with gastrointestinal ulcerations were enrolled and randomly assigned into controlled and supplemented groups. Participants in the controlled group were prescribed esomeprazole (20?mg/qd), while the supplemented group was prescribed esomeprazole (20?mg/qd) and calcitriol (2.5?μg/qd). BMD, serum levels of calcium, carboxy-terminal collagen crosslinks (CTX), and alkaline-phosphatase (ALP) were assessed.

Results: (1) No significant between-group difference of age, gender, smoking, previous glucocorticoid use and hemoglobin level was found; (2) after 10.6?±?0.8?d of PPI therapy, BMD T score in the controlled group was slightly increased compared with initial (?1.25?±?0.08 versus ?1.28?±?0.06, p?=?0.084), while there was no change in the supplemented group (?1.25?±?0.05 versus ?1.26?±?0.03, p?=?0.308); (3) during study termination, calcium level in the supplemented group was slightly higher than the controlled group (2.05?±?0.03?mmol/L versus 2.01?±?0.05?mmol/L, p?=?0.073), while no significant differences of CTX (366.57?±?43.71?pg/mL versus 373.15?±?50.23?pg/mL, p?=?0.036) and ALP were found among these two groups (50.47?±?9.32?U/L versus 52.23?±?10.45?U/L, p?=?0.075).

Conclusion: Patients with gastrointestinal ulcerations with esomeprazole therapy, calcitriol supplement showed no efficacy on BMD changes.     

Role of GABAB receptors and p38MAPK/NF-κB pathway in paclitaxel-induced apoptosis of hippocampal neurons

Context: The effects of the anticancer drug paclitaxel on learning and memory are rarely studied.

Objective: This study investigated changes in GABA_B receptor expression during paclitaxel-induced apoptosis of hippocampal neurons and the role of the p38MAPK/NF-κB pathway in this process.

Materials and methods: Hippocampal neurons isolated from neonatal Sprague–Dawley rats were divided into six groups: Control (C), SB (10?µL of 10-µmol/L SB203580), SN (53?µg/mL SN50), N (1?µmol/L paclitaxel), SB?+?N (10?µmol/L SB203580?+?1?µmol/L paclitaxel) and SN?+?N (53?µg/mL SN50?+?1?µmol/L paclitaxel). Cells in different groups were treated with corresponding agents for 24?h at 37?°C. The apoptosis rate and protein levels of GABA_B1 receptors and NF-κB p65 were evaluated. Rat models of neuropathic pain was induced by paclitaxel and were divided into four groups such as N, B?+?N, SN?+?N and SN?+?B?+?N groups. Rats in the N group received intrathecal injections of normal saline solution. Rats in the B?+?N group received intrathecal injections of 10?μL baclofen (0.05?μg/μL). Rats in the SN?+?N and SN?+?B?+?N groups received intrathecal injections of SN50 and SN50 plus baclofen, respectively. Spatial learning and memory were evaluated in rat models based on the escape latency and the number of crossings over the platform and protein levels of GABA_B1 receptors, NF-κB, IL-1β and TNFα were measured by immunohistochemistry assay and western blot.

Results: The neuronal apoptosis rate was significantly increased in N (49.16?±?3.12)%, SB?+?N (31.18?±?3.02)% and SN?+?N (28.47?±?3.75)% groups, accompanied by increased levels of GABA_B1 receptors and NF-κB p65 (p?p?B1:9.0?±?1.6, NF-κB p65:29.6?±?2.4, IL-1β: 30.4?±?3.4, TNFα: 31.0?±?3.4), B?+?N, SN?+?N and SN?+?B?+?N groups evidently increased levels of GABA_B1 receptor (B?+?N:SN?+?N:SN?+?B?+?N?=?19.4?±?2.1:20.8?±?1.9:28.0?±?1.9) but significantly decreased levels of NF-κB p65 (B?+?N:SN?+?N:SN?+?B?+?N?=?21.2?±?1.5:18.6?±?2.1:12.6?±?1.5), IL-1β (B?+?N:SN?+?N:SN?+?B?+?N?=?22.0?±?1.0:19.6?±?1.8:14.6?±?1.5) and TNF α (B?+?N:SN?+?N:SN?+?B?+?N?=?23.0?±?1.6:22.2?±?0.8:16.6?±?1.7). Similar findings were found in western blot analysis.

Discussions and conclusions: Paclitaxel may reduce cognitive function in rats through the p38MAPK/NF-κB pathway and GABA_B1 receptors.     

Accelerated corneal collagen cross-linking for progressive keratoconus

Purpose: To evaluate the efficacy of accelerated corneal cross-linking (CXL) procedure for progressive keratoconus.

Materials and methods: Twenty-three eyes of 23 patients undergone accelerated CXL procedure were evaluated preoperatively and postoperatively at 1st, 3rd and 6th month for uncorrected distant visual acuity (UDVA), best corrected distant visual acuity (CDVA), spherical error, cylindrical error, spherical equivalent (SE), keratometric values and thinnest corneal thickness (TCT) values with corneal topography by Scheimpflug camera and endothelial cell density (ECD).

Results: The mean UDVA was improved from 0.97?±?0.41 logarithm of minimal angle of resolution (logMAR) to 0.76?±?0.45 logMAR at the 6th month after CXL (p?=?0.332). The mean CDVA was improved from 0.49?±?0.30 logMAR to 0.34?±?0.22 logMAR at the 6th month after CXL (p?=?0.026). The mean sphere was decreased from ?4.47?±?4.1 diopter (D) to ?3.79?±?3.86?D and the mean cylinder was decreased from ?5.60?±?2.2?D to ?4.55?±?1.98?D and the mean SE was decreased from ?7.22?±?4.48?D to ?6.36?±?4.34?D at the 6th month after CXL (p?=?0.128, p?=?0.002 and p?=?0.045, respectively). Flat keratometry, steep keratometry, mean keratometry and maximum keratometry were significantly reduced at the 6th month after CXL (p?=?0.025, p?p?=?0.004 and p?=?0.03, respectively). TCT and ECD were not changed significantly the 6th month after CXL (p?=?0.135 and p?=?0.082, respectively).

Conclusion: Accelerated CXL procedure was effective to stabilize progression of keratoconus with significant reduction in topographic keratometric values and significant increase in CDVA in 6 months.     

Effect of intravitreal injection of dexamethasone implant on corneal endothelium in macular edema due to retinal vein occlusion

Objective: To evaluate the effects of dexamethasone (DEX) implant (Ozurdex®) on corneal endothelium in patients with retinal vein occlusion complicated with macular edema.

Materials and methods: Patients (n?=?31) received 1–3 intravitreal DEX implants in one eye. Measurements were intraocular pressure (IOP) at baseline and 1, 3, and 6 months after the first intravitreal injection and corneal specular microscopy and central corneal thickness (CCT) at baseline and 1 and 6 months. We analyzed endothelial cell density (ECD), coefficient of variation of cell size (CV), and percentage of hexagonality.

Results: Mean follow-up period was 9.7?±?3.3 months. Mean number of injections was 1.5?±?0.8. Mean IOP values were 15.6?±?2.6?mm Hg at baseline, 17.7?±?3.6?mm Hg at one month, 16.4?±?4.1?mm Hg at three months, and 16.0?±?2.7?mm Hg at six months. There was a significant difference in mean IOPs at one month and six months (p?=?0.008). There were no significant differences in mean ECD (p?=?0.375), CV (p?=?0.661), percentage of hexagonality (p?=?0.287), and CCT (p?=?0.331).

Conclusion: Although intravitreal injection of 0.7?mg DEX causes moderate elevation of IOP, it does not seem to have detrimental effects on corneal endothelium at six months.     

24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain

ABSTRACT

Background: Collagen hydrolysate is a nutritional supplement that has been shown to exert an anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis.

Objective: To investigate the effect of collagen hydrolysate on activity-related joint pain in athletes who are physically active and have no evidence of joint disease.

Design and setting: A prospective, randomized, placebo-controlled, double-blind study was conducted at Penn State University in University Park, Pennsylvania. Parameters including joint pain, mobility, and inflammation were evaluated with the use of a visual analogue scale during a 24-week study phase.

Study participants: Between September 2005 and June 2006, 147 subjects who competed on a varsity team or a club sport were recruited. Data from 97 of 147 subjects could be statistically evaluated.

Intervention: One hundred and forty-seven subjects (72 male, 75 female) were randomly assigned to two groups: a group (n?=?73) receiving 25?mL of a liquid formulation that contained 10?g of collagen hydrolysate (CH-Alpha)^* and a group (n?=?74) receiving a placebo, which consisted of 25?mL of liquid that contained xanthan.

Main outcome measures: The primary efficacy parameter was the change in the visual analogue scales from baseline during the study phase in relation to the parameters referring to pain, mobility, and inflammation.

Results: When data from all subjects (n?=?97) were evaluated, six parameters showed statistically significant changes with the dietary supplement collagen hydrolysate (CH) compared with placebo: joint pain at rest, assessed by the physician (CH vs. placebo (–1.37?±?1.78 vs. –0.90?±?1.74 (?p?=?0.025)) and five parameters assessed by study participants: joint pain when walking (–1.11?±?1.98 vs. –0.46?±?1.63, p?=?0.007), joint pain when standing (–0.97?±?1.92 vs. –0.43?±?1.74, p?=?0.011), joint pain at rest (–0.81?±?1.77 vs. –0.39?±?1.56, p?=?0.039), joint pain when carrying objects (–1.45?±?2.11 vs. –0.83?±?1.71, p?=?0.014) and joint pain when lifting (–1.79?±?2.11 vs. –1.26?±?2.09, p?=?0.018). When a subgroup analysis of subjects with knee arthralgia (n?=?63) was performed, the difference between the effect of collagen hydrolysate vs. placebo was more pronounced. The parameter joint pain at rest, assessed by the physician, had a statistical significance level of p?=?0.001 (–1.67?±?1.89 vs. –0.86?±?1.77), while the other five parameters based on the participants’ assessments were also statistically significant: joint pain when walking (?p?=?0.003 (– 1.38?±?2.12 vs. – 0.54?±?1.65)), joint pain when standing (?p?=?0.015 (–1.17?±?2.06 vs. –0.50?±?1.68)), joint pain at rest with (?p?=?0.021 (–1.01 ±1.92 vs. –0.47?±?1.63)), joint pain when running a straight line (?p?=?0.027 (–1.50?±?1.97 vs. –0.80?±?1.66)) and joint pain when changing direction (?p?=?0.026 (–1.87?±?2.18 vs. –1.20?±?2.10)).

Conclusion: This was the first clinical trial of 24-weeks duration to show improvement of joint pain in athletes who were treated with the dietary supplement collagen hydrolysate. The results of this study have implications for the use of collagen hydrolysate to support joint health and possibly reduce the risk of joint deterioration in a high-risk group. Despite the study's size and limitations, the results suggest that athletes consuming collagen hydrolysate can reduce parameters (such as pain) that have a negative impact on athletic performance. Future studies are needed to support these findings.     

Effect of smoking on retina nerve fiber layer and ganglion cell-inner plexiform layer complex

Purpose: The aim of this study is to show the effects of smoking on retina layers, especially retina nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer complex (GCIPL).

Materials and methods: Participants smoking for more than 10 years at least 1 pack of cigarettes a day and a control group, both including participants between ages of 20 and 50 years with no other systemic or ocular diseases were studied. After normality tests, an independent sample t test was used to analyze the differences in age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), GCIPL and RNFL values between the groups.

Results: There were 44 participants in each group. There were 32 (62.5%) men and 12(37.5%) women in smokers and 36 (77.88%) men and 8 (22.22%) women in control group. Mean ages were 39.85?±?8.41 and 38.66?±?10.47 years, mean spherical equivalent (SE) values were ?0.15?±?0.4 and 0?±?0.29 dioptries in smokers and control groups, respectively. The IOP, AXL, GCIPL and RNFL values were 17.58?±?3.41?mmHg, 23.69?±?0.56?mm, 84.3?±?5.83?μm and 92.3?±?3.51?μm in the smokers group and 18.5?±?2.91?mmHg, 23.45?±?0.72?mm, 86.11?±?8.02?μm and 97.66?±?8.23?μm in the control group. The inferior, superior, nasal and temporal values of RNFL quadrants were 123.18?±?26.14, 117.05?±?5.51, 64.95?±?8.67 and 63.5?±?6.88?μm in the smokers group and 130.81?±?11.8, 123.55?±?11.03, 72.44?±?9.84 and 58.44?±?7.48?μm in the control group. There were no significant difference of age, sex, SE, IOP, AXL and GCIPL values between the smokers and control groups (p?>?0.05). The mean RNFL was significantly thinner in the smokers group compared to controls (p?=?0.03, independent t test). Inferior and superior quadrants of RNFL decreased in smokers group (p?=?0.01 and p?=?0.03, respectively) but temporal and nasal quadrants did not seem to be changed (p?=?0.96 and p?=?0.07, respectively).

Discussion: Smoking may affect RNFL thickness but not GCIPL.     

Swept-source optical coherence tomography analysis in asthmatic children under inhaled corticosteroid therapy

Purpose: To evaluate retinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), subfoveal choroidal thickness (SFCT), and central retinal thickness (CRT) in asthmatic children who were under inhaled corticosteroid treatment by using Swept-Source Optical Coherence Tomography (SS-OCT).

Material and methods: Fifty-three children were prospectively analyzed in the study. Group 1 included 31 asthmatic children and group 2 included 22 healthy children. Asthmatic children received a dose 250?μg daily of inhaled fluticasone propionate (Flexotide, GlaxoSmithKline, Middlesex, UK). Allergy parameters including, exposure to smoke, eosinophil count, percentage of eosinophils, immunoglobuline (Ig) E levels, number of asthma attacks, number of sensitivity to allergens and follow-up time were recorded. The RNFLT, GCLT, SFCT, and CRT were analyzed with SS-OCT and the data were compared between the groups.

Results: There were 13 girls (41.9%) and 18 boys (58.1%) in group 1 and 13 girls (59.1%) and 9 boys (40.9%) in group 2 (p?=?0.22). The mean age was 9.3?±?2.2 years in group 1 and 9.9?±?1.5 years in group 2 (p?=?0.08). The mean CRT (239.26?±?34.56 µm versus 226.82?±?26.23 µm, p?=?0.22) and mean SFCT (273.97?±?40.95 µm versus 280.41?±?32.78 µm, p?=?0.54) did not significantly differ between the groups. The superior, inferior, and average RNFLT were significantly lower in group 1 than group 2 (p?p?p?Conclusions: The SS-OCT revealed that asthmatic children under inhaled corticosteroid treatment have lower RNFLT than healthy subjects.     

In vitro glucuronidation of aprepitant: a moderate inhibitor of UGT2B7

Abstract

1.?Aprepitant, an oral antiemetic, commonly used in the prevention of chemotherapy-induced nausea and vomiting, is primarily metabolized by CYP3A4. Aprepitant glucuronidation has yet to be evaluated in humans. The contribution of human UDP-glucuronosyltransferase (UGT) isoforms to the metabolism of aprepitant was investigated by performing kinetic studies, inhibition studies and correlation analyses. In addition, aprepitant was evaluated as an inhibitor of UGTs.

2.?Glucuronidation of aprepitant was catalyzed by UGT1A4 (82%), UGT1A3 (12%) and UGT1A8 (6%) and K_ms were 161.6?±?15.6, 69.4?±?1.9 and 197.1?±?28.2?µM, respectively. Aprepitant glucuronidation was significantly correlated with both UGT1A4 substrates anastrazole and imipramine (r_s?=?0.77, p?<?0.0001 for both substrates; n?=?44), and with the UGT1A3 substrate thyroxine (r_s?=?0.58, p?<?0.0001; n?=?44).

3.?We found aprepitant to be a moderate inhibitor of UGT2B7 with a K_i of ～10?µM for 4-MU, morphine and zidovudine. Our results suggest that aprepitant can alter clearance of drugs primarily eliminated by UGT2B7. Given the likelihood for first-pass metabolism by intestinal UGT2B7, this is of particular concern for oral aprepitant co-administered with oral substrates of UGT2B7, such as zidovudine and morphine.     

Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea

Objective The present study aimed to compare the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and saxagliptin on 24?hour acute glucose fluctuations in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with a combination of metformin and sulfonylurea.

Research design and methods This was a 24 week, prospective, randomized, open-label, active-controlled study. Patients (N?=?73) with T2DM who had inadequate glycemic control (HbA1c 7.0%–10.0%) with a stable dosage of metformin plus gliclazide for more than 3 months were randomized to receive either vildagliptin 50?mg twice daily (BID, n?=?37) or saxagliptin 5?mg once daily (QD, n?=?36). Change in mean amplitude of glycemic excursions (MAGE) was assessed at the end of 24 weeks.

Results At baseline, the mean (±SD) age was 62.9?±?6.55 years, disease duration was 7.0?±?2.33 years, and HbA1c was 8.4?±?0.68%. After 24 weeks of treatment, the MAGE decreased from 5.81?±?1.16?mmol/L to 4.06?±?0.86?mmol/L (p<0.001) in the vildagliptin group and from 5.66?±?1.14?mmol/L to 4.79?±?1.25?mmol/L (p?=?0.003) in the saxagliptin group. The mean change in MAGE in the vildagliptin group was significantly greater than that in the saxagliptin group (1.74?±?0.48?mmol/L vs. 0.87?±?0.40?mmol/L, p<0.001). The mean change in HbA1c, from baseline to the study endpoint, in the vildagliptin and saxagliptin groups, was 1.22?±?0.40% and 1.07?±?0.36%, respectively, with no significant difference between the groups (p?=?0.091). The overall safety and tolerability of vildagliptin and saxagliptin were similar. The limitations of the study were a small number of patients and open-label administration of the study drug.

Conclusion Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese patients with T2DM.

Chinese clinical trial registration number ChiCTR-TRC-13003858.     

Enrichment of Bifidobacterium longum subsp. infantis ATCC 15697 within the human gut microbiota using alginate-poly-l-lysine-alginate microencapsulation oral delivery system: an in vitro analysis using a computer-controlled dynamic human gastrointestinal model

Abstract

This study evaluates alginate-poly-l-lysine-alginate Bifidobacterium longum subsp. infantis ATCC 15697-loaded microcapsules to enrich the human gut microbiota. The cell survival of alginate-poly-l-lysine-alginate microencapsulated B. infantis ATCC 15697 in gastric acid, bile, and through human gastrointestinal transit was investigated, as well as the formulation’s effect on the gut microbiota. Results show that microencapsulation increases B. infantis ATCC 15697 cell survival at pH1.0 (33.54?±?2.80% versus <1.00?±?0.00%), pH1.5 (41.15?±?2.06% versus <1.00?±?0.00%), pH2.0 (60.88?±?1.73% versus 36.01?±?2.63%), pH3.0 (75.43?±?1.23% versus 46.30?±?1.43%), pH4.0 (71.40?±?2.02% versus 47.75?±?3.12%) and pH5.0 (73.88?±?3.79% versus 58.93?±?2.26%) (p?<?0.05). In addition, microencapsulation increases cell survival at 0.5% (76.85?±?0.80% versus 70.77?±?0.64%), 1.0% (59.99?±?0.97% versus 53.47?±?0.58%) and 2.0% (53.10?±?1.87% versus 44.59?±?1.52%) (p?<?0.05) (w/v) bile. Finally, daily administration of alginate-poly-l-lysine-alginate microencapsulated B. infantis ATCC 15697 in a human gastrointestinal model induces a significant enrichment of B. infantis within the ascending (184.51?±?17.30% versus 53.83?±?17.82%; p?<?0.05), transverse (174.79?±?25.32% versus 73.17?±?15.30%; p?<?0.05) and descending (94.90?±?25.22% versus 46.37?±?18.93%; p?>?0.05) colonic microbiota.     

Exenatide effects on diabetes,obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years

ABSTRACT

Background: Exenatide, an incretin mimetic for adjunctive treatment of type 2 diabetes (T2DM), reduced hemoglobin A_1c (A1C) and weight in clinical trials. The objective of this study was to evaluate the effects of?≥?3 years exenatide therapy on glycemic control, body weight, cardiometabolic markers, and safety.

Methods: Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended, open-label clinical trial. Patients were randomized to twice daily (BID) placebo, 5?µg exenatide, or 10?µg exenatide for 30 weeks, followed by 5?µg exenatide BID for 4 weeks, then 10?µg exenatide BID for ≥3 years of exenatide exposure. Patients continued metformin and/or sulfonylureas.

Results: 217 patients (64% male, age 58?±?10 years, weight 99?±?18?kg, BMI 34?±?5?kg/m², A1C 8.2?±?1.0% [mean?±?SD]) completed 3 years of exenatide exposure. Reductions in A1C from baseline to week 12 (?1.1?±?0.1% [mean?±?SEM]) were sustained to 3 years (?1.0?±?0.1%; p?<?0.0001), with 46% achieving A1C?≤?7%. Exenatide progressively reduced body weight from baseline (?5.3?±?0.4?kg at 3 years; p?<?0.0001). Patients with elevated serum alanine aminotransferase (ALT) at baseline (n?=?116) had reduced ALT (?10.4?±?1.5?IU/L; p?<?0.0001) and 41% achieved normal ALT. Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline (?6.1?±?0.6?kg vs. ?4.4?±?0.5?kg; p?=?0.03), however weight change was minimally correlated with baseline ALT (r?=??0.01) or ALT change (r?=?0.31). Homeostasis Model Assessment B (HOMA-B), blood pressure, and aspartate aminotransferase (AST) all improved. A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n?=?151). Triglycerides decreased 12% (p?=?0.0003), total cholesterol decreased 5% (p?=?0.0007), LDL-C decreased 6% (p?<?0.0001), and HDL-C increased 24% (p <?0.0001). Exenatide was generally well tolerated. The most frequent adverse event was mild-to-moderate nausea. The main limitation of this study is the open-label, uncontrolled nature of the study design which does not provide a placebo group for comparison.

Conclusion: Adjunctive exenatide treatment for ≥3 years in T2DM patients resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.     

Effect of topiramate on choroidal thickness and anterior chamber parameters in the treatment of patients with migraine

Objective: To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine.

Methods: A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation.

Results: Mean age of the patients was 40.2?±?6.5?years. Mean CT at central fovea was 324?±?47?μm initially, 341?±?45?μm in the first month and 344?±?46?μm in the second month, thus first and second month measures were significantly higher than base values (p?p?=?0.001). Baseline ACD (3.66?±?0.22?mm) measures significantly decreased at the first month (3.63?±?0.22?mm) and second month (3.62?±?0.22?mm, p?=?0.009). Also, a significant reduction was detected in the first (36.2?±?4.9°) and second month (35.9?±?5.1°) ACA measures comparing with baseline (39.1?±?5.1°, p?=?0.05). A significant myopic shift was determined in the first and second month SphEq values (?0.08?±?0.6, ?0.10?±?0.6, respectively, p?=?0.05).

Conclusions: The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.     

Oxidative stress parameters and serum magnesium levels in patients with seasonal allergic conjunctivitis

Objective: To evaluate oxidative stress parameters and serum magnesium (Mg) levels in patients with seasonal allergic conjunctivitis (SAC) during the pollen season.

Methods: This observational cross-sectional study involved 35 patients with SAC without any other ocular and systemic diseases, and 38 consecutive, age- and sex-matched healthy subjects. Serum malondialdehyde (MDA), adjusted ischemia modified albumin (IMA), and Mg levels were quantified, and the results were compared between the groups.

Results: No significant differences were found between the groups with respect to age (p?=?0.416) and sex (p?=?0.362). Serum MDA and adjusted IMA levels of the subjects with SAC (69.54?±?7.71 μM and 0.74?±?0.39 ABSU) were significantly higher than the control group (64.61?±?5.89 μM and 0.57?±?0.19 ABSU) (p?=?0.002 and p?=?0.025, respectively). There was no significant difference for serum Mg levels between the groups (p?=?0.177).

Conclusion: We demonstrated higher levels of oxidative stress parameters in patients with SAC compared to the control group, which imply a possible role of oxidative stress in the pathogenesis of SAC.     

Spectral domain-optical coherence tomographic findings in patients with ankylosing spondylitis under anti-tumor necrosis factor-alpha therapy

Objective: To evaluate the effect of tumor necrosis factor-alpha (TNF-α) blockade on the thickness of the peripapillary retinal nerve fiber layer (RNFL), the ganglion cell-inner plexiform layers (GCIPL), and the macula in ankylosing spondylitis (AS) patients under anti-TNF-α therapy.

Materials and methods: Twenty-one patients with AS received etanercept, or adalimumab, or infliximab for at least 6 months. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were measured before and 6 months after the beginning of the treatment. Peripapillary RNFL, four regional fields (superior, inferior, nasal, and temporal), GCIPL, and macular thicknesses of the patients were analyzed by optical coherence tomography before the treatment, at 3 months and 6 months after the beginning of the treatment.

Results: The mean BASDAI, ESR, and CRP values were 5.2?±?1.5, 31.6?±?21.7, and 15.7?±?13.9, respectively, at the beginning of the treatment and 2.3?±?1.7, 21.3?±?15.1, and 10.1?±?10.3, respectively, 6 months after the beginning of treatment. There were significant differences among the mean BASDAI, ESR, and CRP values at the beginning of treatment and 6 months later (p?p?=?0.007, and p?=?0.009, respectively). There were no significant differences among peripapillary RNFL (p?=?0.24), four regional fields (p?=?0.98, p?=?0.23, p?=?0.09, p?=?0.47), GCIPL (p?=?0.25), or macular (p?=?0.33) thicknesses of the patients during anti-TNF-α treatment. In addition, the mean intraocular pressure levels throughout the follow-up did not show significant variation on repeated-measures ANOVA (p?=?0.77).

Conclusions: TNF-α blockade does not seem to influence RNFL, GCIPL, or macular thickness of patients with AS in the short term.     

Effect of oral photochemotherapy (8-methoxypsoralen + UVA) on the electrophysiologic function of retina

Context: Since we had observed electroretinographic (ERG) abnormalities in some patients undergoing photochemotherapy with normal eye examination, we decided to investigate the effects of this therapy on retinal function.

Objective: To investigate the effects of oral photochemotherapy (8-methoxypsoralen?+?Ultraviolet-A) on electrophysiologic function of retina.

Materials and methods: Patients with vitiligo, psoriasis or eczema were enrolled. Patients with any abnormal eye exam or a positive drug or family history for retinal disease were excluded. Baseline standard ERG was provided with the RETIport32 device. The second ERG was performed 6 months after the first and at least 1 week after the last photochemotherapy session (mean number of sessions: 45?±?11). The outcome measures were changes in rod response, standard combined response, single-flash cone response, 30-Hz flicker (N1-P1) and oscillatory potentials amplitudes.

Results: Forty patients were enrolled; 20 of them (mean age: 31.1?±?12 years) completed the study. The mean rod response b-wave amplitude decreased from 88.9?±?47.5 to 86.4?±?36.6 and standard combined response b-wave amplitude decreased from 266.52 to 261.85?µV (p?=?0.422 and p?=?0.968, respectively) and the standard combined response a-wave amplitude increased from 155.4?±?40.0 at baseline to 165.1?±?48.4 in the follow-up ERG (p?=?0.092). The mean single-flash cone response a-wave amplitude decreased insignificantly in the follow-up ERG trace (34.5?±?13.7 and 29?±?15.4, respectively, p?=?0.242). The mean single-flash cone response b-wave amplitude showed an insignificant increase (p?=?0.087). The amplitudes of 30-Hz flicker wave and oscillatory potentials did not change significantly in the follow-up ERG (p?=?0.551 and p?=?0.739, respectively).

Conclusion: Since no significant change in ERG traces was observed, oral photochemotherapy seems safe for retinal electrophysiologic function.