Therapeutic Effect Of Oral Administration Research Articles

P0193 Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice

Abstract Background Ulcerative colitis (UC) belongs inflammatory disease with chronic and relapsing characterizations and increased-cancer risk. CX5461 has been demonstrated the important roles in autoimmune disease, immunological rejection, and macrophage-mediated vascular inflammation. However, whether CX5461 can serve as UC therapeutic drug remains unclear. The objective of this study is to investigate the therapeutic effect of oral administration of SFELNVs@CX5461 on DSS-induced colitis and its possible molecular mechanism. Methods SFELNVs were extracted and the morphology were charactered. The preparation of SFELNVs@CX5461 were electroporated and the loading efficiency of SFELNVs@CX5461 were calculated. We conducted the experiments using SFELNV, CX5461 and SFELNVs@CX5461 respectively. Proliferation and apoptosis of RAW264.7 cells were detected by flow cytometry according to the kits. C57BL/6 mice (8 weeks, 18-20g) were induced by 3% DSS in drinking water for a week to establish the colitis model. Then, DSS-induced C57BL/6 colitis mice models were orally administrated with SFELNVs@CX5461 (n=5, 80mg/kg) and SFELNVs (n=5, 80mg/kg) for 5 days. The body weight, consistency of stool, and rectal bleeding were measured each day. Finally, after sacrificing the mice, colons and main organs were obtained for the qPCR, HE, and IHC. Results Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, Oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, Oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 enhanced the treatment efficacy of mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1β, and IL-6) expression and promoting M2 macrophage infiltration. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe and effective UC therapy. Conclusion In summary, SFELNVs@CX5461 represents a therapeutic strategy to UC with excellent biocompatibility due to the ability to enhance anti-inflammatory effects in vitro and in vivo to alleviate UC.

Lactiplantibacillus plantarum P101 Ameliorates TiO2 NP-Induced Bone Injury in Young Rats by Remodeling the Gut Microbiota and Inhibiting the Production of Pro-Inflammatory Cytokines.

To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO2 NPs), and explore the potential mechanism. Four-week-old male rats were orally administration to TiO2 NPs and supplemented with P101 2hours later for 4weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota. Our results showed that TiO2 NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO2 NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO2 NPs. This study showed that the mechanism by which P101 alleviates bone damage caused by TiO2 NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response.

Better therapeutic effect of oral administration of GS441524 compared with GC376

FIP is a fatal feline disease caused by FIPV. Two drugs (GS441524 and GC376) target FIPV and have good therapeutic effect when administered by subcutaneous injection. However, subcutaneous injection has limitations compared with oral administration. Additionally, the oral efficacy of the two drugs has not been determined. Here, GS441524 and GC376 were shown to efficiently inhibit FIPV-rQS79 (recombination virus with a full-length field type I FIPV and the spike gene replaced with type II FIPV) and FIPV II (commercially available type II FIPV 79–1146) at a noncytotoxic concentration in CRFK cells. Moreover, the effective oral dose was determined via the in vivo pharmacokinetics of GS441524 and GC376. We conducted animal trials in three dosing groups and found that while GS441524 can effectively reducing the mortality of FIP subjects at a range of doses, GC376 only reducing the mortality rate at high doses. Additionally, compared with GC376, oral GS441524 has better absorption, slower clearance and a slower rate of metabolism. Furthermore, there was no significant difference between the oral and subcutaneous pharmacokinetic parameters. Collectively, our study is the first to evaluate the efficacy of oral GS441524 and GC376 using a relevant animal model. We also verified the reliability of oral GS441524 and the potential of oral GC376 as a reference for rational clinical drug use. Furthermore, the pharmacokinetic data provide insights into and potential directions for the optimization of these drugs.

Therapeutic effects of oral administration of lytic Salmonella phages in a mouse model of non-typhoidal salmonellosis.

Acute non-typhoidal salmonellosis (NTS) caused by a Gram-negative bacterium Salmonella enterica serovar Typhimurium (S. Tm) is one of the most common bacterial foodborne diseases worldwide. Bacteriophages (phages) can specifically target and lyse their host bacteria, including the multidrug-resistant strains, without collateral damage to other bacteria in the community. However, the therapeutic use of Salmonella phages in vivo is still poorly investigated. Salmonella phages ST-W77 and SE-W109 have previously been shown by our group to be useful for biocontrol properties. Here, we tested whether phages ST-W77 and SE-W109 can reduce Salmonella invasion into cultured human cells and confer a therapeutic benefit for acute NTS in a mammalian host. Human colonocytes, T84 cells, were treated with phages ST-W77, SE-W109, and its combination for 5 min before S. Tm infection. Gentamicin protection assays demonstrated that ST-W77 and SE-W109 significantly reduced S. Tm invasion and inflammatory response in human colonocytes. Next, streptomycin-pretreated mice were orally infected with S. Tm (108 CFU/mouse) and treated with a single or a combination of ST-W77 and SE-W109 (1010 PFU/mouse for 4 days) by oral feeding. Our data showed that phage-treated mice had lower S. Tm numbers and tissue inflammation compared to the untreated mice. Our study also revealed that ST-W77 and SE-W109 persist in the mouse gut lumen, but not in systemic sites. Together, these data suggested that Salmonella phages ST-W77 and SE-W109 could be further developed as an alternative approach for treating an acute NTS in mammalian hosts.

Display of quintuple glucagon-like peptide 1 (28-36) nonapeptide on Bacillus subtilis spore for oral administration in the treatment of type 2 diabetes.

To develop an oral delivery system of glucagon-like peptide 1 (GLP-1) (28-36) for treating type-2 diabetes, B.S-GLP-1(28-36), a recombinant Bacillus subtilis spores transformed with a plasmid vector encoding five consecutive GLP-1 (28-36) nonapeptides with an enterokinase site was constructed. GLP-1(28-36) nonapeptide was successfully expressed on the surface of B. subtilis spores and validated by Western blot and immunofluorescence. The therapeutic effect of oral administration of B.S-GLP-1(28-36) spores was evaluated in type 2 diabetic model mice. The efficacy of recombinant spores was examined for a period of 13weeks after oral administration in diabetic mice. At the end of the sixth week, diabetic mice with oral administration of BS-GLP-1(28-36) spores showed decreased blood glucose levels from 2·4×10- 2 moll-1 to 1·7×10- 2 moll-1 . By the ninth week, the mean fasting blood glucose level in the experimental group was significantly lower than that in the control group 30min after injection of pyruvate. At the end of the 10th week of oral administration, the blood glucose of the experimental group was significantly lower than that of the control group after intraperitoneal injection of glucose. By the 12th week, fasting blood glucose level and fasting insulin level were measured in all mice, the results showed that the recombinant spores increased the insulin sensitivity of mice. The results of pathological observation showed that the recombinant spores also had a certain protective effect on the liver and islets of mice, and the content of GLP-1(28-36) in the pancreas of the experimental group was increased. The results of this study revealed that GLP-1(28-36) nonapeptides can reduce blood glucose and play an important role in the treatment of type 2 diabetes.

Oral Administration of the p75 Neurotrophin Receptor Modulator, LM11A-31, Improves Erectile Function in a Mouse Model of Cavernous Nerve Injury

BackgroundRadical prostatectomy for prostate cancer can not only induce cavernous nerve injury (CNI), but also causes cavernous hypoxia and cavernous structural changes, which lead to a poor response to phosphodiesterase 5 inhibitors. AimTo investigate the therapeutic effect of oral administration of LM11A-31, a small molecule p75 neurotrophin receptor (p75NTR) ligand and proNGF antagonist, in a mouse model of bilateral CNI, which mimics nerve injury–induced erectile dysfunction after radical prostatectomy. Methods8-week-old male C57BL/6 mice were divided into sham operation and CNI groups. Each group was divided into 2 subgroups: phosphate-buffered saline and LM11A-31 (50 mg/kg/day) being administered once daily starting 3 days before CNI via oral gavage. 2 weeks after CNI, we measured erectile function by electrical stimulation of the bilateral cavernous nerve. The penis was harvested for histologic examination and Western blot analysis. The major pelvic ganglia was harvested and cultured for assays of ex vivo neurite outgrowth. OutcomesIntracavernous pressure, neurovascular regeneration in the penis, in vivo or ex vivo functional evaluation, and cell survival signaling were measured. ResultsErectile function was decreased in the CNI group (44% of the sham operation group), while administration of LM11A-31 led to a significant improvement of erectile function (70% of the sham operation group) in association with increased neurovascular content, including cavernous endothelial cells, pericytes, and neuronal processes. Immunohistochemical and Western blot analyses showed significantly increased p75NTR expression in the dorsal nerve of CNI mice, which was attenuated by LM11A-31 treatment. Protein expression of active PI3K, AKT, and endothelial nitric oxide synthase was increased, and cell death and c-Jun N-terminal kinase signaling was significantly attenuated after LM11A-31 treatment. Furthermore, LM11A-31 promoted neurite sprouting in cultured major pelvic ganglia after lipopolysaccharide exposure. Clinical ImplicationsLM11A-31 may be used as a strategy to treat erectile dysfunction after radical prostatectomy or in men with neurovascular diseases. Strengths & LimitationsUnlike biological therapeutics, such as proteins, gene therapies, or stem cells, the clinical application of LM11A-31 would likely be relatively less complex and low cost. Our study has some limitations. Future studies will assess the optimal dosing and duration of the compound. Given its plasma half-life of approximately 1 hour, it is possible that dosing more than once per day will provide added efficacy. ConclusionSpecific inhibition of the proNGF-p75NTR degenerative signaling via oral administration of LM11A-31 represents a novel therapeutic strategy for erectile dysfunction induced by nerve injury.Yin GN, Ock J, Limanjaya A, et al. Oral Administration of the p75 Neurotrophin Receptor Modulator, LM11A-31, Improves Erectile Function in a Mouse Model of Cavernous Nerve Injury. J Sex Med 2021;18:17–28.

1076-P: A 12-Week Treatment with Ciclosporin A Improves Insulin Secretion in Patients with Adult-Onset Autoimmune Diabetes: An Open-Label, Single-Arm, Pilot Study

Objectives: Adult-onset autoimmune diabetes, defined as having latent autoimmune diabetes in adults (LADA), is characterized by a less intensive autoimmune process, in which a lymphocytic infiltration of the exocrine pancreas is involved. immunosuppressive agents may have potential therapeutic benefit. This is a pilot study examining the therapeutic effects of ciclosporin A on insulin secretion in patients with LADA. Methods: The study was an open label, single arm, pilot trial. A total of 18 patients (12 men and 6 women with mean age of 40.6 yrs old) diagnosed with LADA were prospectively evaluated. All patients underwent insulin treatment at least for 3 months without any oral anti-hyperglycemic agent. All patients were prescribed ciclosporin A (50mg/day) for 12 weeks. Serum C-peptide concentrations were measured at baseline and 3 months after ciclosporin A intervention. We also evaluated total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Cre) before and after ciclosporin A treatment. The primary outcome of the study was the change in serum C-peptide concentrations. Results: A total of 17 patients completed the study. One patient was withdrawn at day 32 due to discontinuation of medication. Serum fasting C-peptide concentrations significantly increased from 0.12 ng/ml up to 0.32 ng/ml (P<0.001). After 12-week ciclosporin A intervention, there was no significant difference on TBIL (14.65 vs. 12.83umol/L, P>0.05), DBIL (4.70 vs. 4.65 umol/L, P>0.05), AST (17.41 vs. 17.82 U/L, p>0.05), ALT (18.19 vs. 18.08 U/L, p>0.05), or Cre (67.40 vs. 67.53 umol/L, P>0.05) compared with the corresponding baseline levels. Conclusions: This pilot study demonstrates the potential therapeutic effects of oral administration of ciclosporin A for patients with LADA. Larger, controlled studies are needed to verify the findings. Disclosure L. Zhang: None. W. Meng: None. S. Chen: None. Y. Yang: None. J. Wang: None. Y. Dong: None.

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Ulcerative colitis (UC) is a chronic and etiologically refractory inflammatory gut disorder. Although berberine, an isoquinoline alkaloid, has been revealed to exert protective effects on experimental colitis, the underlying molecular mechanism in chronic intestinal inflammation remains ill-defined. This study was designed to uncover the therapeutic efficacy and immunomodulatory role of berberine in chronic UC. Therapeutic effects of oral administration of berberine were investigated in dextran sodium sulfate (DSS)-induced murine chronic UC and the underlying mechanisms were further identified by si-OSMR transfection in human intestinal stromal cells. Berberine significantly attenuated the experimental symptoms and gut inflammation of chronic UC. Berberine treatment could also maintain the intestinal barrier function and rectify tissue fibrosis. In accordance with infiltrations of antigen-presenting cells (APCs), innate lymphoid cells (ILCs), and activated NK cells in colonic lamina propria, increased expression of OSM and OSMR were observed in the inflamed tissue of chronic UC, which were decreased following berberine treatment. Moreover, berberine inhibited the overactivation of human intestinal stromal cells through OSM-mediated JAK-STAT pathway, which was obviously blocked upon siRNA targeting OSMR. The research provided an infusive mechanism of berberine and illustrated that OSM and OSMR intervention might function as the potential target in chronic UC.

Therapeutic Effect of Oral Administration and External Therapy of Traditional Chinese Medicine on Cervical Tuberculous

Objective: To analyze the clinical effect and value of oral administration and external therapy of traditional Chinese medicine for treatment of cervical tuberculous lymphadenopathy. Methods: A total of 56 patients with cervical tuberculous lymphadenopathy admitted to our hospital from January 1 to January 2018 were recruited. By using double-blind method, the patients were divided into control group (n=28) and experimental group (n=28). Control group comprised of patients with conventional anti-tuberculosis treatment, while the experimental group comprised of patients treated with oral administration and external therapy of traditional Chinese medicine. Total effective rate, incidence of complication and level of T lymphocyte subsets were compared between the two groups of cervical tuberculous lymphadenopathy patients. Results: Post-treatment data of total effective rate, complication rate, CD3+, CD4+, CD8+, CD4+/CD8+ of the experimental group were compared with the control group. P<0.05; statistical analysis showed statistical significance. Post-treatment data of CD3+, CD4+, CD8+, CD4+/CD8+ of both control and experimental groups were compared with pre-treatment data. P<0.05; statistical analysis showed statistical significance. Conclusion: Oral administration and external therapy of traditional Chinese medicine possesses significant effect in treatment of cervical tuberculous lymphadenopathy.

1147-P: Effect of Short-Term Ciclosporin A Treatment on Insulin Secretion in Patients with Adult-Onset Autoimmune Diabetes: An Open-Label, Single-Arm, Pilot Study in China

Adult-onset autoimmune diabetes, defined as having latent autoimmune diabetes in adults (LADA), is characterized by a less intensive autoimmune process, in which a lymphocytic infiltration of the exocrine pancreas is involved. Immunosuppressive agents may have potential therapeutic benefit. This is a pilot study examining the therapeutic effects of oral administration of ciclosporin A on insulin secretion in patients with LADA. The study was an open label, single arm, pilot trial. A total of 12 patients (8 men and 4 women with mean age of 40.2 years old) diagnosed with LADA were prospectively evaluated. All patients underwent insulin treatment at least for 3 months without any oral anti-hyperglycemic agent. Serum C-peptide concentrations were measured at baseline and after ciclosporin A intervention. We also evaluated clinical parameters including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Cre) before and after ciclosporin A treatment. The primary outcome of the study was the change in serum C-peptide concentrations. A total of 12 patients completed the study. No patient was withdrawn. Serum fasting C-peptide concentrations significantly increased from 0.10 ng/ml up to 0.32 ng/ml, following treatment with ciclosporin A (50mg/day) for 4 weeks (P<0.001). After 4-week ciclosporin A intervention, there was no significant difference on TBIL (14.33 vs. 13.70 umol/L, P=0.59), DBIL(4.31 vs. 4.63 umol/L, P=0.48), AST(16.83 vs. 18.50 U/L, p=0.09), ALT(17.17 vs. 18.16 U/L, p=0.35), or Cre (67.17 vs. 66.01 umol/L, P=0.25) compared with the corresponding baseline levels. This pilot study demonstrates the potential therapeutic effects of oral administration of ciclosporin A for patients with LADA. No significant adverse effects of the drug were observed. Larger, controlled studies are needed to verify the results. Disclosure L. Zhang: None. J. Wang: None. N. Wang: None. Y. Yang: None. X. Yin: None. Y. Dong: None.

Investigation of the efficiency and safety of tilmicosin phosphate in treating experimental mycoplasmal infections in pigs

In order to evaluate the in vivo therapeutic effect of oral administration of tilmicosin phosphate on mycoplasmal pneumonia in swine and its safety for the infected swine, the model of mycoplasmal pneumonia disease in swine was established by artificial infection, and indices such as efficiency, cure rate, death rate, the score of lung lesion, and the routine blood tests, blood biochemistry, and routine urine tests of tested swine were determined. The results showed that all of the dosage groups of 100 mg/L, 80 mg/L, 60 mg/L of 10% tilmicosin phosphate soluble powder demonstrated distinct therapeutic effects on mycoplasmal pneumonia in pigs, significantly reducing the scores of lung lesions in diseased pigs, and that the treatment effect of 60-80 mg/L tilmicosin phosphate soluble powder was equivalent to that of 10% tilmicosin soluble powder. Administration of 10% tilmicosin phosphate soluble powder improved the weight gain of the diseased swine. Treatment of infected pigs with 60?100 mg/L of 10% tilmicosin phosphate soluble powder did not seem to influence the routine blood tests, biochemical index, and routine urine tests, and is therefore safe for diseased swine. In conclusion, administration of 10% tilmicosin phosphate soluble powder is effective and safe to treat artificially infected swine with mycoplasmal pneumonia.

Therapeutic Effects of Bifidobacterium Longum Kacc 91563 on Dncb-Induced Atopic Dermatitis-Like Skin Lesions in Nc / Nga Mice

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe itch. This study was designed to evaluate the therapeutic effects of oral administration of Bifidobacterium longum, KACC 91563 (BLK) on 2, 4-dinitrochlorobenzene (DNCB) - induced AD-like skin lesions in NC / Nga mice. Three doses of BLK (333, 1667, and 3334 mg / kg / day, 7 times a week) were orally administrated to mice with DNCB-induced AD. The therapeutic effect of BLK was assessed by measuring skin AD score, scratching behavior, serum IgE levels, as well as the expression of COX-2, TNF-α, IL-4, IL-10, and IL-12 by immunohistochemistry. AD score, scratching frequency, serum IgE level, COX-2, TNF-α, IL-4, IL-10, and IL-12 increased in mice with DNCB-induced AD. BLK alleviated AD-like symptoms such as skin severity of AD score and scratching behaviors. In addition, BLK reduced IgE, COX-2, and TNF-α, IL-4, IL-10, and IL-12 expression. These results suggest that oral administration of BLK has beneficial therapeutic effects for AD patients.

Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study

BackgroundGlutathione plays crucial roles in the detoxification and antioxidant systems of cells and has been used to treat acute poisoning and chronic liver diseases by intravenous injection. This is a first study examining the therapeutic effects of oral administration of glutathione in patients with nonalcoholic fatty liver disease (NAFLD).MethodsThe study was an open label, single arm, multicenter, pilot trial. Thirty-four NAFLD patients diagnosed using ultrasonography were prospectively evaluated. All patients first underwent intervention to improve their lifestyle habits (diet and exercise) for 3 months, followed by treatment with glutathione (300 mg/day) for 4 months. We evaluated their clinical parameters before and after glutathione treatment. We also quantified liver fat and fibrosis using vibration-controlled transient elastography. The primary outcome of the study was the change in alanine aminotransferase (ALT) levels.ResultsTwenty-nine patients finished the protocol. ALT levels significantly decreased following treatment with glutathione for 4 months. In addition, triglycerides, non-esterified fatty acids, and ferritin levels also decreased with glutathione treatment. Following dichotomization of ALT responders based on a median 12.9% decrease from baseline, we found that ALT responders were younger in age and did not have severe diabetes compared with ALT non-responders. The controlled attenuation parameter also decreased in ALT responders.ConclusionsThis pilot study demonstrates the potential therapeutic effects of oral administration of glutathione in practical dose for patients with NAFLD. Large-scale clinical trials are needed to verify its efficacy.Trial registrationUMIN000011118 (date of registration: July 4, 2013).

Protection effect of intracellular melanin from Lachnum YM156 and Haikunshenxi capsule combination on adenine-induced chronic renal failure in mice

This study aimed to elucidate the therapeutic effects of oral administration of intracellular melanin from Lachnum YM156 (LIM) on chronic renal failure (CRF) in mice. The cytotoxicity of LIM was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. CRF was induced in mice by chronic dietary adenine intake. We have used this intervention to explore the effects of oral treatment with LIM (100 and 200 mg kg-1) in CRF mice. The treatment with LIM alone and a combination of Haikunshenxi capsule (HC) add LIM increased the concentration levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and glutathione reductase (GSH), reduced malonaldehyde (MDA) in the nephridial tissues and also reduced the nephridial levels of tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), and interleukin (IL)-6, and the activities of inducible nitric oxide synthase (iNOS). Interestingly, the HC and LIM combination produced a higher therapeutic effect than HC alone. The mechanism of the reported salutary effects of LIM in adenine-induced CRF is associated with amelioration of the adenine induced inflammation and oxidative stress. The present findings recommend that LIM is a useful natural product which can be used to enhance the protection function of HC in CRF mice.

Therapeutic effect of tyndallized Lactobacillus rhamnosus IDCC 3201 on atopic dermatitis mediated by down-regulation of immunoglobulin E in NC/Nga mice.

The therapeutic effect of oral administration of Lactobacillus rhamnosus IDCC 3201 tyndallizate (RHT3201) on atopic dermatitis (AD)-like skin lesions in NC/Nga mice were investigated. After induction of dermatitis in NC/Nga mice with house-dust mite extract, each group was fed RHT3201 with 1 × 10(8) , 1 × 10(9) , or 1 × 10(10) cells orally once a day for 8 weeks. Dermatitis scores and frequency of scratching were improved by oral feeding with RHT3201. In contrast to the control group, RHT3201-fed mice showed significantly down-regulated mast cell numbers and serum immunoglobulin E (IgE) concentrations had significantly less IL4 in their axillary lymph node cells. The therapeutic effect of RHT3201 was found to be dose-dependent. These findings indicate that RHT3201 has potential for treating AD.

Oral administration of PDX1 confers protection against insulitis in the non-obese diabetic (NOD) mice

Type 1 diabetes is a T cell-mediated organ-specific autoimmune disease. Antigen-specific immune intervention allows the selective targeting of autoreactive T cell, while leaving the remainder of the immune system intact. However, immune intervention for type 1 diabetes has not yielded perfect results clinically. In our paper published previously, we asked whether pancreatic duodenal home box 1 (PDX1) is a target of anti-islet autoimmunity in type 1 diabetes. In this experiment, we assessed the therapeutic effect of oral administration of PDX1 on diabetes development of 4-week-old non-obese diabetic (NOD) mice. The results indicate that PDX1 immunization is an effective intervention strategy for delaying the onset of diabetes in NOD mice in association with: 1) reduced insulitis; 2) suppression of destructive autoreactive T cells; 3) augmentation of regulatory T cells; 4) a shift in cytokine production. The present observations suggest that immunization with PDX1 modulates immune cell responses in NOD mice, raising the possibility that it is beneficial in ameliorating autoimmune destruction of beta-cells and delaying type 1 diabetes development clinically.

Oral administration of carbonic anhydrase I ameliorates murine experimental colitis induced by Foxp3−CD4+CD25− T cells

IBDs are thought to involve uncontrolled innate and adaptive immunity against intestinal self-antigens and bacterial antigens. Mouse CA I is a major cecal bacterial antigen in fecal extracts and is implicated in the pathogenesis of IBD. We show here that oral tolerization to CA I induced antigen-specific protection from intestinal inflammation in a murine model. Oral administration of CA I but not irrelevant antigen (KLH) ameliorated CD4(+)CD25(-) T cell transfer murine colitis and DSS-induced murine colitis. Next, we investigated the mechanisms involved in the therapeutic effects of oral administration, such as induction of ALDH1a2, transcription factors, cytokines, CD103(+)CD11c(+) DCs, and generation of Tregs. Oral administration of CA I induced ALDH1a2 mRNA expression in the MLN and colon. When compared with PBS-treated mice, CA I-treated mice had higher Foxp3(+)CD4(+)CD25(+) Treg and CD103(+)CD11c(+) DC numbers in the MLN and colon; had higher TGF-β production in the MLN and colon; had lower RORγt mRNA expression in the MLN and colon; and had lower IL-17 mRNA expression and production in the MLN. These results demonstrate that oral administration of CA I induced antigen-specific immune tolerance by generating Foxp3(+)CD4(+)CD25(+) Tregs and inhibiting Th17 cells in a murine colitis model, thus suggesting that oral tolerization with CA I is an effective therapeutic strategy for IBD regulation.

Oral administration and external application of Chinese drugs combined with micro-invasive operation for the treatment of varicose ulcers in the lower extremities

To evaluate the clinical therapeutic effects of oral administration and external application of Chinese drugs combined with micro-invasive surgery for the treatment of varicose ulcers in the lower extremities (ecthyma). A total of 152 patients (163 limbs) suffering from varicose ulcers on the lower limbs were assigned to two groups according to the patients' willingness. The 102 cases (109 limbs) in the treatment group underwent the method of endovenous microwave closure of communicating veins combined with oral administration and external application of Chinese drugs before and after the operation. The 50 cases (54 limbs) in the control group, were treated with oral administration and external application of Chinese drugs only. Clinical manifestations, including the condition of ulcer healing, the improvement conditions of alogotrophy, edema and other symptoms, were observed before and after 3 months of treatment. The clinical healing rate, the ulcer healing time, and the ulcer recurrence rate, were compared between the two groups. All the patients were followed-up 3 months after treatment. The follow-up was carried out for 3 to 42 months (mean 30.5 months). In the treatment group, 99 patients (106 limbs) were clinically cured, and the clinical healing rate was 97.06%; the ulcer healing time was 9-101 days (average 31.25+/-8.28 days) and 3 cases (5 limbs) had recurrence; the ulcer recurrence rate was 5.81%. In the control group, 40 patients (43 limbs) were clinically cured, with a clinical healing rate of 80.00%; the ulcer healing time was 10-152 days (average 50.60+/-12.31 day) and 5 cases (7 limbs) recurred, with the ulcer recurrence rate being 20.59%. The effects in the treatment group were obviously better than those in the control group (P<0.01 or P<0.05). The oral administration and external application of Chinese drugs combined with micro-invasive surgery for the treatment of varicose ulcers in the lower extremities has a significant curative effect, with a higher clinical healing rate, shorter ulcer healing time and lower ulcer recurrence rate than either treatment alone.

Lactobacillus casei secreting alpha-MSH induces the therapeutic effect on DSS-induced acute colitis in Balb/c Mice.

The neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-alpha-MSH on the colitis, L. casei or L. casei-alpha-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-alpha-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45+/-0. 2 g; L. casei-alpha- MSH: 18.2+/-0.12 g), colitis score (DSS alone: 3.6+/-0.4; L. casei-alpha-MSH: 1.4+/-0.6), MPO activity (DSS alone: 42.7+/-4.5 U/g; L. casei-alpha-MSH: 10.25+/-0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappaB activation. The alpha-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

1207: The Therapeutic Effect of Oral Administration of L-Arginine on Bladder Dysfunction in Diabetic Rats

You have accessJournal of UrologyDiscussed Poster, Tuesday, May 24, 2005, 1:00 - 5:00 pm1 Apr 20051207: The Therapeutic Effect of Oral Administration of L-Arginine on Bladder Dysfunction in Diabetic Rats Kazumasa Torimoto, Hiroko Matsuyoshi, Yukio Hayashi, Hitoshi Masuda, Yoshihiro Matsumoto, Kiyohide Fujimoto, Yoshihiko Hirao, William C. de Groat, Michael B. Chancellor, and Naoki Yoshimura Kazumasa TorimotoKazumasa Torimoto More articles by this author , Hiroko MatsuyoshiHiroko Matsuyoshi More articles by this author , Yukio HayashiYukio Hayashi More articles by this author , Hitoshi MasudaHitoshi Masuda More articles by this author , Yoshihiro MatsumotoYoshihiro Matsumoto More articles by this author , Kiyohide FujimotoKiyohide Fujimoto More articles by this author , Yoshihiko HiraoYoshihiko Hirao More articles by this author , William C. de GroatWilliam C. de Groat More articles by this author , Michael B. ChancellorMichael B. Chancellor More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)35352-7AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1207: The Therapeutic Effect of Oral Administration of L-Arginine on Bladder Dysfunction in Diabetic Rats." The Journal of Urology, 173(4S), p. 327 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 327 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Kazumasa Torimoto More articles by this author Hiroko Matsuyoshi More articles by this author Yukio Hayashi More articles by this author Hitoshi Masuda More articles by this author Yoshihiro Matsumoto More articles by this author Kiyohide Fujimoto More articles by this author Yoshihiko Hirao More articles by this author William C. de Groat More articles by this author Michael B. Chancellor More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF downloadLoading ...