Effect of different ratios of phytogenic feed additives on growth performance, nutrient digestibility, intestinal barrier integrity, and immune response in weaned pigs challenged with a pathogenic Escherichia coli.

This study was conducted to investigate the effects of supplementing different ratios of phytogenic feed additives (PFA) to weaned pigs challenged with pathogenic Escherichia coli on growth performance, nutrient digestibility, intestinal barrier integrity, and immune response, and to determine the optimal mixing ratio for post-weaning diarrhea (PWD) prevention. A total of 48 4-wk-old weaned pigs with initial body weight of 8.01 ± 0.39 kg were placed in individual metabolic cages, and then randomly assigned to eight treatment groups. The eight treatments were as follows: a basal diet without E. coli challenge (negative control, NC), a basal diet with E. coli challenge (positive control, PC), PC with supplementing 0.1% mixture of 20% bitter citrus extract (BCE), 10% microencapsulated blend of thymol and carvacrol (MEO), and 70% excipient (T1), PC with supplementing 0.1% mixture of 10% MEO, 20% premixture of grape seed and grape marc extract, green tea, and hops (PGE), and 60% excipient (T2), PC with supplementing 0.1% mixture of 10% BCE, 10% MEO, 10% PGE, and 70% excipient (T3), PC with supplementing 0.1% mixture of 20% BCE, 20% MEO, and 60% excipient (T4), PC with supplementing 0.1% mixture of 20% MEO, 20% PGE, and 60% excipient (T5), and PC with supplementing 0.1% mixture of 10% BCE, 20% MEO, 10% PGE, and 60% excipient (T6). The experiments progressed in 16 days, including 5 days before and 11 days after the first E. coli challenge (day 0). In the E. coli challenge treatments, all pigs were orally inoculated by dividing a total of 10 mL of E. coli F 18 for three consecutive days from day 0 postinoculation (PI). Compared with the PC group, the PFA2 and PFA6 groups significantly increased (P < 0.05) feed efficiency and decreased (P < 0.05) diarrhea during the entire period. At day 11 PI, the PFA6 group significantly improved (P < 0.05) gross energy digestibility compared to the PFA1 group. The PFA6 group significantly decreased (P < 0.05) tumor necrosis factor α (TNF-α) and interleukin-6 in serum and increased (P < 0.05) the villus height to crypt depth ratio (VH:CD). The PFA2 significantly decreased (P < 0.05) the relative protein expression of calprotectin in the ileum. In conclusion, improvements in growth performance, diarrhea reduction, and immunity enhancement are demonstrated when 10% BCE, 20% MEO, 10% PGE, and 60% excipient are mixed.

Phytogenic feed additives (PFA) include various herbs and spices, such as essential oils and polyphenols. Flavonoids and polyphenols contained in PFA are generally known to have antioxidant and antibacterial actions and based on this, PFA is considered an alternative to antibiotics in the swine industry. Pathogenic Escherichia coli infection is one of the most important causes of post-weaning diarrhea (PWD) in pigs. PWD causes intestinal damage, which leads to severe diarrhea, reduced growth performance, and mortality in weaned pigs, resulting in significant financial loss to the swine industry. Therefore, this study was conducted to investigate the effects of supplementing different ratios of PFA to weaned pigs challenged with E. coli and determine the optimal mixing ratio for PWD prevention. Our study results showed that growth performance was improved when supplementing a mixture of 10% bitter citrus extract (BCE), 20% microencapsulated blend of thymol and carvacrol (MEO), 10% premixture of grape seed and grape marc extract, green tea, and hops (PGE), and 60% excipient. Also, the effect of improving the immune response and intestinal morphology was shown. In conclusion, a mixture of 10% BCE, 20% MEO, 10% PGE, and 60% excipients is considered the optimal mixing ratio.

Phytogenic feed additives alleviate pathogenic Escherichia coli-induced intestinal damage through improving barrier integrity and inhibiting inflammation in weaned pigs.

BACKGROUND: This study was conducted to investigate the effects of each phytogenic feed additive (PFA; PFA1, bitter citrus extract; PFA2, a microencapsulated blend of thymol and carvacrol; PFA3, a mixture of bitter citrus extract, thymol, and carvacrol; PFA4, a premixture of grape seed, grape marc extract, green tea, and hops; PFA5, fenugreek seed powder) on the growth performance, nutrient digestibility, intestinal morphology, and immune response in weaned pigs infected with Escherichia coli (E. coli). RESULTS: A total of 63 4-week-old weaned pigs were placed in individual metabolic cages and assigned to seven treatment groups. The seven treatments were as follows: 1) NC; basal diet without E. coli challenge, 2) PC; basal diet with E. coli challenge, 3) T1; PC + 0.04% PFA1, 4) T2; PC + 0.01% PFA2, 5) T3; PC + 0.10% PFA3, 6) T4; PC + 0.04% PFA4, 7) T5; PC + 0.10% PFA5. The experiments lasted in 21 d, including 7 d before and 14 d after the first E. coli challenge. In the E. coli challenge treatments, all pigs were orally inoculated by dividing a total of 10 mL of E. coli F18 for 3 consecutive days. The PFA-added groups significantly increased (P < 0.05) average daily gain and feed efficiency and decreased (P < 0.05) the fecal score at d 0 to 14 post-inoculation (PI). Tumor necrosis factor α was significantly lower (P < 0.05) in the PFA-added groups except for T1 in d 14 PI compared to the PC treatment. The T3 had a higher (P < 0.05) immunoglobulin G and immunoglobulin A concentration compared to the PC treatment at d 7 PI. Also, T3 showed significantly higher (P < 0.05) villus height:crypt depth and claudin 1 expression in ileal mucosa, and significantly down-regulated (P < 0.05) the expression of calprotectin compared to the PC treatment. CONCLUSIONS: Supplementation of PFA in weaned pigs challenged with E. coli alleviated the negative effects of E. coli and improved growth performance. Among them, the mixed additive of bitter citrus extract, thymol, and carvacrol showed the most effective results, improving immune response, intestinal morphology, and expression of tight junctions.

Stimbiotic supplementation modulated intestinal inflammatory response and improved boilers performance in an experimentally-induced necrotic enteritis infection model.

BACKGROUND: Two experiments were conducted to establish an optimal NE challenge model and evaluate the efficacy of stimbiotic (STB) supplementation in necrotic enteritis (NE) challenged broilers. In Exp. 1, a total of 120 Arbor Acres (AA) broilers (45.0 ± 0.21 g) were randomly assigned to 6 treatments in a 3 × 2 factorial arrangement. Vaccine treatments included non-challenge (0), × 10 the recommended dose (× 10) or × 20 the recommended dose (× 20) by the manufacturer. Clostridium perfringens (CP) treatments were non-challenge (No) or 3 mL of 2.2 × 107 CFU CP challenge (Yes). In Exp. 2, a total of 72 AA broilers (40.17 ± 0.27 g) were randomly assigned to 6 treatments in a 3 × 2 factorial arrangement. Dietary treatments included non-additive (CON), 100 mg/kg STB (STB) and 100 mg/kg STB on top of a typical commercial blend including an essential oil, probiotics, and enzyme (CB). Challenge treatments included non-NE challenge (No) and NE challenge (Yes) as established in Exp. 1. RESULTS: In Exp. 1, CP and vaccine challenge decreased (P < 0.05) body weight (BW), body weight gain (BWG) and feed intake (FI), and increased (P < 0.05) the number of broilers with diarrhea and intestinal lesions. The oral administration of × 20 recommended dose of vaccines coupled with 3 mL of 2.2 × 107 CFU CP resulted in (P < 0.01) a significantly increased incidence of wet litter and intestinal lesions. Thus, this treatment was chosen as the challenge model for the successful inducement of NE in Exp. 2. In Exp. 2, the NE challenge negatively affected (P < 0.01) growth performance, ileal morphology, immunoglobulin contents in blood, caecal microbiota in the caecum, footpad dermatitis, intestinal lesion scores, tumour necrosis factor (TNF-α) and endotoxin in the serum compared with the non-NE challenged birds. The supplementation of STB and CB in diets enhanced (P < 0.05) growth performance, intestinal microbiota, and blood profiles by stimulating ileal morphology (VH and VH:CD) and propionate production in the cecum, and there were no differences in measured variables between STB and CB supplemented birds. CONCLUSION: Overall, these results indicate that STB supplementation was able to reduce the inflammatory response and improve the performance of NE challenged birds, and the supplementation of STB alone was as effective as a typical commercial blend containing a number of other additives.

Effects of different Bacillus licheniformis and Bacillus subtilis ratios on nutrient digestibility, fecal microflora, and gas emissions of growing pigs.

The objective of this study was to evaluate the effects of different mixing ratios of Bacillus licheniformis and Bacillus subtilis in diets on nutrient digestibility, fecal microflora, and odor gas emissions of growing pigs. A total of four crossbred ([Landrace × Yorkshire] × Duroc) barrows with average body weight (BW) of 41.2 ± 0.7 kg were randomly allotted four diets over four periods in a 4 × 4 Latin square design. Treatments were as follows: Control (CON, basal diet), CON + 0.2% probiotic complex (L4S6, B. licheniformis and B. subtilis at a 4:6 ratio), CON + 0.2% probiotic complex (L5S5, B. licheniformis and B. subtilis at a 5:5 ratio), CON + 0.2% probiotic complex (L6S4, B. licheniformis and B. subtilis at a 6:4 ratio). Dietary probiotic supplementation showed higher crude protein (CP) digestibility values and lower Escherichia coli counts in fecal samples than the CON group (p < 0.05). There was no significant difference in NH3 or H2S emission until day 3. The positive effect of H2S and NH3 emissions was detected earlier with the L4S6 and L5S5 compared to the L6S4, which had a lower ratio of B. subtilis. Both the L4S6 and L5S5 probiotic complexes significantly decreased the fecal H2S and NH3 emission in days 4 and 6 (p < 0.05). On day 7, all probiotic complexes decreased (p < 0.05) H2S and NH3 emissions than the CON group. Our results agreed that the dietary supplementation of Bacillus licheniformis and Bacillus subtilis complexes in growing pigs can significantly improve CP digestibility and reduce fecal E. coli counts, NH3 and H2S emissions. Notably, the higher mixing ratio of Bacillus subtilis in probiotic supplementation is more effective in reducing the odor of manure.

Effect of insect protein and protease on growth performance, blood profiles, fecal microflora and gas emission in growing pig.

Two experiments were conducted to determine the effect of Hermetia illucens larvae (HIL) as protein and protease on growth performance, blood profiles, fecal microflora, and gas emission in growing pig. In experiment 1, the seventy-two crossbred growing pigs ([Landrace × Yorkshire] × Duroc) with an initial body weight (BW) of 27.98 ± 2.95 kg were randomly allotted to one of four dietary treatments (3 pigs per pen and 6 replicates pen per treatments). The experimental design was a 2 × 2 factorial arrangement of treatments evaluating two diets (Poultry offal diets and HIL diets) without or with supplementing protease. The poultry offal in basal diet has been replaced by HIL. In experiment 2, the four crossbred growing pigs ([Landrace × Yorkshire] × Duroc) with an initial BW of 28.2 ± 0.1 kg were individually accepted in stainless steel metabolism cages. The dietary treatments included: 1) PO- (PO-; poultry offal diet), 2) PO+ (PO- + 0.05% protease), 3) HIL- (3% PO of PO- diet was replacement 3% HIL), 4) HIL+ (HIL- + 0.05% protease). In experiment 1, From weeks 0 to 2, average daily gain (ADG) and feed efficiency (G:F) were significantly increased in the PO diet group compared with the HIL group. From weeks 2 to 4, ADG and G:F were higher for protease group than for non-protease group. At weeks 2 and 4, the PO diet group had lower blood urea nitrogen (BUN) levels than HIL diet group. In experiment 2, crude protein (CP) and nitrogen (N) retention were decreased by HIL diet at weeks 2 and 4. The fecal microflora and gas emission were not affected by HIL and protease. The HIL diet showed lower CP digestibility than PO diet and total essential amino acids digestibility tended to higher in PO diet than HIL diet. In summary, the present study revealed that replacement of the PO protein with the HIL protein and the additive of protease in growing pig diets during the overall experimental period had no negative effect.

The Effect of Lifestyle Changes on Blood Pressure Control among Hypertensive Patients.

BACKGROUND: Hypertension is highly prevalent among patients who visit primary care clinics. Various factors and lifestyle behaviors are associated with effective blood pressure control. We aimed to identify factors and lifestyle modifications associated with blood pressure control among patients prescribed antihypertensive agents. METHODS: This survey was conducted at 15 hospital-based family practices in Korea from July 2008 to June 2010. We prospectively recruited and retrospectively assessed 1,453 patients prescribed candesartan. An initial evaluation of patients' lifestyles was performed using individual questions. Follow-up questionnaires were administered at 4, 8, and 12 weeks. We defined successful blood pressure control as blood pressure <140 mm Hg systolic and <90 mm Hg diastolic. RESULTS: Of the 1,453 patients, 1,139 patients with available data for initial and final blood pressures were included. In the univariate analysis of the change in performance index, weight gain (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.52 to 3.11; P<0.001), physical inactivity (OR, 1.195; 95% CI, 1.175 to 3.387; P=0.011), and increased salt intake (OR, 1.461; 95% CI, 1.029 to 2.075; P=0.034) were related to inadequate blood pressure control. Salt intake also showed a significant association. Multivariate ORs were calculated for age, sex, body mass index, education, income, alcohol consumption, smoking status, salt intake, comorbidity, and family history of hypertension. In the multivariate analysis, sex (OR, 3.55; 95% CI, 2.02 to 6.26; P<0.001), salt intake (OR, 0.64; 95% CI 0.43 to 0.97; P=0.034), and comorbidity (OR, 1.82; 95% CI, 1.23 to 2.69; P=0.003) were associated with successful blood pressure control. CONCLUSION: Weight gain, physical inactivity, and high salt intake were associated with inadequate blood pressure control.

Roots extracts of Adenophora triphylla var. japonica improve obesity in 3T3-L1 adipocytes and high-fat diet-induced obese mice.

OBJECTIVE: To investigate the anti-obesity activity and the action mechanism of the roots of Adenophora triphylla var. japonica extract (ATE) in high-fat diet (HFD)-induced obese mice and 3T3-L1 adipocytes. METHODS: The roots of Adenophora triphylla were extracted with 70% ethanol. To demonstrate the compounds, linoleic acid was analyzed by using gas chromatography; and the anti-obesity effects and possible mechanisms of ATE were examined in 3T3-L1 adipocytes and HFD-induced obese mice. RESULTS: Treatment with ATE inhibited the lipid accumulation without cytotoxicity in 3T3-L1 adipocytes. Furthermore, 200 and 400 mg/kg ATE treatment significantly decreased the body weight gain, white adipose tissues (WATs) weight and plasma triglyceride level, while 100 and 200 mg/kg ATE treatment increased the plasma high-density lipoprotein cholesterol level in the HFD-induced obese mice, as compared with the HFD group. Treatment with 200 and 400 mg/kg ATE also lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in liver. ATE treatment showed significantly lower expression level of adipogenesis-related proteins, such as peroxisome proliferator-activated receptor γ, fatty acid binding protein (aP2), fatty acid synthase in 3T3-L1 adipocytes; and furthermore, decreased peroxisome proliferator-activated receptor γ, aP2, fatty acid synthase, sterol regulatory element binding protein-1c, and lipoprotein lipase mRNA expression levels in WAT of the HFD-induced obese mice. CONCLUSIONS: These results suggested that the ATE has an anti-obesity effect, which may be elicited by regulating the expression of adipogenesis and lipogenesis-related genes and proteins in adipocytes and WAT of the HFD-induced obese mice.

Efficacy of the mineral oil and hyaluronic acid mixture eye drops in murine dry eye.

PURPOSE: To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE). METHODS: Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining. RESULTS: There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group. CONCLUSIONS: The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE.

Higher order aberrations of the corneal surface after laser subepithelial keratomileusis.

PURPOSE: To evaluate the changes of higher order aberrations (HOAs) before and after laser subepithelial keratomileusis (LASEK) and to analyze the influence of tear film instability on HOAs of the corneal surface after LASEK. METHODS: In this cross-sectional study, 31 patients who underwent LASEK were divided into dry eye (16 patients, 32 eyes) and non-dry eye groups (15 patients, 30 eyes). Uncorrected distance visual acuity, spherical equivalent refraction, ablation depth, tear film parameters and Ocular Surface Disease Index (OSDI) questionnaire scores were evaluated in both groups. Total HOA root mean square (RMS), third-order coma, third-order trefoil and fourth-order spherical aberration (SA) of the corneal surface immediately and at 10 seconds after blinking were measured before and after surgery. RESULTS: The total HOA RMS, coma, trefoil and SA significantly increased after LASEK compared with preoperative values in both groups. In the dry eye group, total HOA RMS, coma and trefoil significantly increased except for SA at 10 seconds after blinking compared with those measured immediately after blinking. In addition, the changes of total HOA RMS, coma and trefoil were negatively correlated with tear film break-up time (R = -0.420, -0.473 and -0.439, respectively), but positively correlated with OSDI score (R = 0.433, 0.499 and 0.532, respectively). In the non-dry eye group, there were no significant differences between HOAs measured at 10 seconds after blinking and those measured immediately after blinking. CONCLUSIONS: The HOAs including coma, trefoil and SA significantly increased after LASEK. The tear film instability in the dry eye can be associated with more deterioration of the optical quality after LASEK, due to more significant increase of total HOA RMS, coma and trefoil.

Effect of hypotonic 0.18% sodium hyaluronate eyedrops on inflammation of the ocular surface in experimental dry eye.

PURPOSE: To investigate the efficacy of hypotonic 0.18% sodium hyaluronate (SH) eyedrops in a mouse model of experimental dry eye (EDE). METHODS: EDE was induced in C57BL/6 mice by a subcutaneous scopolamine injection and an air draft. The mice were divided into 4 groups according to topical treatment regimens: EDE control, isotonic 0.5% carboxymethycellulose (CMC), isotonic 0.1% SH, and hypotonic 0.18% SH. Tear volume, corneal smoothness, and corneal staining scores were measured at 5 and 10 days of EDE. Multiplex immunobead assay, immunohistochemistry, and flow cytometry for proinflammatory cytokines, chemokines, and inflammatory molecules were performed at 10 days of EDE. RESULTS: The 0.18% SH group had a significantly lower corneal smoothness and staining scores than the 0.5% CMC and 0.1% SH groups at 10 days of EDE (P<0.05). The 0.18% SH group showed significantly low levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, monokine induced by interferon-γ, and interferon-γ-inducible protein 10 compared with the other groups (P<0.05). The mean percentages of CD4(+)CXCR3(+), CD40(+), and CD44(+) cells in the conjunctiva were significantly lower in the 0.18% SH group than in the other groups (P<0.05). In addition, the 0.1% SH group showed lower levels of TNF-α and IL-1ß and percentages of CD40(+) and CD44(+) cells than the EDE and 0.5% CMC groups. CONCLUSIONS: Hypotonic 0.18% SH eyedrops are more effective in improving ocular surface irregularity and staining and decreasing inflammatory cytokines, chemokines, and cells on the ocular surface compared with isotonic 0.5% CMC or 0.1% SH eyedrops in the treatment of EDE.

Histological changes after treatment for localized fat deposits with phosphatidylcholine and sodium deoxycholate.

Phosphatidylcholine (PPC) and sodium deoxycholate (DC) injections have been used cosmetically to reduce localized fat, but to date, few studies have addressed the histological effect of human fat tissue following injections of PPC and DC. We injected PPC and DC mixed with normal saline into the patient's abdominal area. Examinations of postinjection tissue revealed marked changes within the subcutaneous fat. We observed important microscopic evidence of substitution of fat by fibrosis, marked inflammatory infiltration with microabscess formation in the dermis, and septal and lobular panniculitis with thick fibrous septa. Fat necrosis with microcalcification and cyst formation were observed in the subcutaneous fat. Fibroid necrosis with extravasation was noted in the small vessels around fat necrosis. Therefore, careful use of PPC and DC is recommended when patients want to cosmetically reduce localized fat.

Achieving recommended low density lipoprotein cholesterol goals and the factors associated with target achievement of hypercholesterolemia patients with rosuvastatin in primary care.

OBJECTIVE: Hypercholesterolemia is a major risk factor for cardiovascular disease and requires continuous management. The role of primary physicians in this regard is important, yet the factors associated with successful lipid lowering treatments in primary clinics have not been clearly identified. We aimed to evaluate the rate of successful hypercholesterolemia treatment in Korean primary care, and to identify the factors associated with achieving low density lipoprotein cholesterol (LDL-C) targets. METHODS: We prospectively recruited and retrospectively assessed 1851 Korean patients with hypercholesterolemia who visited family physicians and were prescribed rosuvastatin for the first time. LDL-C lowering targets, defined according to NCEP ATP III guidelines, were evaluated at 6 months after the first prescription. The factors associated with achieving these targets were also assessed. RESULTS: Overall, 87.6% of our participants attained their LDL-C goals. In multiple logistic regression analysis, good adherence to medication was strongly associated with the achievement of target LDL-C levels, whereas higher cardiovascular risk factors including diabetes (in both sexes), low high density lipoprotein, and current smoking status (in males), and hypertension (in females) were related to LDL-C target level failures. CONCLUSION: Our observations of the short period for hypercholesterolemia in Korean primary care has revealed that the rate of achieving target LDL-C levels was high in these patients, whereas patients at higher risk for cardiovascular disease tended to have lower LDL-C achievement outcomes. Primary care physicians should pay more attention to patients showing higher cardiovascular risk and stress the need for good adherence and management regimens in these individuals.

Therapeutic effect of topical adiponectin in a mouse model of desiccating stress-induced dry eye.

PURPOSE: To investigate the therapeutic effect of topical adiponectin in a mouse model of experimental dry eye (EDE). METHODS: EDE was created by desiccating stress in 6- to 8-week old female C57BL/6 mice. Eye drops consisting of 0.0001%, 0.001%, or 0.01% adiponectin, or balanced salt solution (BSS), were applied in EDE. Tear volume and corneal irregularity score were measured at 5 and 10 days after treatment. Levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monokine induced by interferon-γ (MIG) were measured in the conjunctiva and lacrimal gland using a multiplex immunobead assay at 10 days. Periodic acid-Schiff staining, immunohistochemistry, and flow cytometry were also performed. RESULTS: Mice treated with 0.001% or 0.01% adiponectin showed a significant improvement in tear volume and corneal irregularity compared with the EDE control and BSS-treated groups. A significant decrease in the levels of IL-1ß, IL-6, TNF-α, IFN-γ, and MIG and staining intensity of TNF-α was observed in the 0.001% and 0.01% adiponectin-treated groups, compared with the other groups, in the conjunctiva and lacrimal gland. In the 0.001% and 0.01% adiponectin-treated groups, the density of conjunctival goblet cells was higher and the number of CD4+CXCR3+ T cells was lower than in the other groups. However, there were no significant differences in all parameters between the 0.0001% adiponectin and control groups. CONCLUSIONS: Topical application of adiponectin can markedly improve clinical signs and decrease inflammation in the ocular surface and lacrimal gland of EDE, suggesting that adiponectin eye drops may be used as a therapeutic agent for dry eye disease.

Effectiveness of topical infliximab in a mouse model of experimental dry eye.

PURPOSE: To investigate the efficacy of a topical anti-tumor necrosis factor-α agent, infliximab, in a mouse model of experimental dry eye (EDE). METHODS: EDE was induced in C57BL/6 mice, with or without topical treatment consisting of balanced salt solution or 0.001%, 0.01%, or 0.1% infliximab solutions. Tear volume and corneal smoothness were measured on days 5 and 10 after treatment. Levels of interleukin (IL)-1ß, IL-6, IL-17, and interferon γ (IFN-γ) were measured in the conjunctiva using a multiplex immunobead assay 10 days after treatment. Periodic acid-Schiff staining, immunohistochemistry, and flow cytometry were also performed 10 days after treatment. RESULTS: Mice treated with 0.01% or 0.1% infliximab showed a significant improvement in tear volume and corneal smoothness compared with controls. The 0.01% and 0.1% infliximab-treated groups showed decreased levels of conjunctival IL-1ß, IL-6, IL-17, and interferon γ and a decreased staining intensity of tumor necrosis factor-α. The density of conjunctival goblet cells was higher, whereas the number of CD4*CXCR3* T cells was lower, in the 0.01% and 0.1% infliximab-treated groups compared with the EDE and balanced salt solution control groups. However, there was no significant difference in all parameters between the 0.001% infliximab-treated group and control group. CONCLUSIONS: : Topical application of infliximab can improve tear production and ocular surface irregularity, decrease inflammatory cytokines and cells on the ocular surface, and increase conjunctival goblet cell density. These results suggest that topical infliximab eye drops at a concentration of 0.01% and 0.1% may be useful for the treatment of dry eye disease.

Clinical effect of a mixed solution of sodium hyaluronate and sodium carboxymethylcellulose during the transconjunctival approach for orbital wall reconstruction.

This study aimed to evaluate the anti-adhesive effect of a mixed solution of sodium hyaluronate and sodium carboxymethylcellulose (HACMC, Guardix-sol®) during the transconjunctival approach to orbital wall reconstruction. Eighty-seven patients who underwent orbital wall reconstruction by the transconjunctival approach were enrolled in this prospective study. We applied HACMC between the orbicularis oculi muscle and the orbital septum after surgery in 47 patients and did not use it in 40 patients. Lower lid retraction and marginal reflex distance 2 (MRD(2)) were measured to analyze the degree of postoperative adhesion at 1 week and 1, 3, and 6 months. The degree of MRD(2) showed clinically significant differences at postoperative 1 week and 1 month between the HACMC and control groups (p<0.05). Lower lid ectropion developed in two patients (5.0%) in the control group but did not occur in the HACMC group. In orbital wall reconstruction by the transconjunctival approach, the HACMC mixture solution is effective for preventing adhesion and lower lid ectropion during the early postoperative period.

The prevalence of osteoporosis in Korean adults aged 50 years or older and the higher diagnosis rates in women who were beneficiaries of a national screening program: the Korea National Health and Nutrition Examination Survey 2008-2009.

For the prevention of osteoporotic fracture, adequate screening and treatment are important. However, there are few published data on diagnosis and treatment rates of osteoporosis in Asia. We used data from the fourth Korea National Health and Nutrition Examination Survey 2008-2009 to estimate the nationwide prevalence, physician diagnosis rate, and treatment rate of osteoporosis in adults aged 50 years and older. The bone mineral density (BMD) measurements of central skeletal sites (lumbar spine, femoral neck, and total hip) were obtained using dual-energy X-ray absorptiometry (DXA) (Discovery-W; Hologic Inc., Waltham, MA, USA). Diagnosis of osteopenia or osteoporosis was defined by the World Health Organization (WHO) T-score criteria. The prevalence of osteoporosis in adults aged 50 years or older was 35.5% in women and 7.5% in men. The prevalence of osteoporosis in Korea was similar to other East Asian countries but higher than that in Caucasians. Lumbar spine bone density T-scores tended to be lower than those of the femoral neck or hip. The estimated diagnosis rate was 26.2% (women 29.9%, men 5.8%) and the treatment rate was 12.8% (women 14.4%, men 4.0%). The physician diagnosis rate was significantly higher in females aged 66 to 68 years who were the beneficiaries of the national screening program than that in females of other ages (43.6% versus 28.1%, p < 0.05). The national screening program for osteoporosis may have contributed to an increased diagnosis rate in older Korean women. However, it was evident that treatment following a diagnosis of osteoporosis was still inadequate.

The influence of Sam-Chil-Geun (Panax notoginseng) on the serum lipid levels and inflammations of rats with hyperlipidemia induced by poloxamer-407.

PURPOSE: Atherosclerosis is characterized by the progressive deposition of lipids and inflammatory process. We attempted to develop a chemically-induced hyperlipidemic mice model, using poloxamer-407 and evaluated the lipid lowering and anti-inflammatory effect of P. notoginseng compared with that of atorvastatin, an antihyperlipidemic drug. MATERIALS AND METHODS: Male Wistar rats were randomly divided into 5 groups: control group without any intervention (normal), poloxamer 500 mg/kg i.p. (P), poloxamer plus atorvastatin 1.34 mg/kg p.o. (P + ST), poloxamer plus P. notogin-seng 40 mg/kg p.o. (P + NG40), and poloxamer plus P. notoginseng 100 mg/kg p.o. (P + NG100). After 3 weeks, we measured serum total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, interleukin (IL)-1, tumor necrosis factor (TNF)-alpha levels, and reports of cyclo-oxygenase (COX)-2 and intercellular adhesion molecule (ICAM) appearances in each group. RESULTS: After 3 weeks, serum cholesterol levels significantly decreased in P + ST and P + NG40 groups. Significant decrease of LDL level was only noted in the P + ST group. P + ST, P + NG40, and P + NG100 also had decreased serum triglyceride levels; however, P + ST and P + NG40 showed no statistical difference of the triglyceride lowering effect. The results of IL-1 and TNF-alpha and the appearance of COX-2 and ICAM were statistically not different in each group. CONCLUSION: P. notoginseng 40 mg/kg showed significantly lowering effects on serum total cholesterol and triglyceride levels. We suggest a well-designed study showing the effects of regulating blood lipids with combined administration of P. notoginseng and statin-drug.

Development of a rating system for digestive system impairments: Korean Academy of Medical Sciences Guideline.

A systematic and effective welfare system for people with digestive system impairments is required. In Korea, an objective and scientific rating guideline does not exist to judge the digestive system impairments. Whether the impairments exist or not and the degree of it need to be examined. Thus, with these considerations we need a scientific rating guideline for digestive system impairments to fit our cultural and social background. In 2007, a research team, for the development of rating impairment guidelines, was organized under the supervision of Korean Academy of Medical Sciences. The rating guidelines for digestive system impairments was classified into upper and lower gastrointestinal tracts impairments and liver impairment. We developed objective rating guidelines for the upper gastrointestinal tract, the impairment generated after surgery for the stomach, duodenum, esophagus, and for the lower gastrointestinal tract, the impairment generated after construction and surgery for colon, rectum, anus, and intestinal stomas. We tried to make the rating impairment guidelines to include science, objectivity, convenience, rationality, and actuality. We especially emphasized objectivity as the most important value. We worked to make it easy and convenient to use for both the subjects who received the impairment ratings and the doctors who will give the ratings.