L-Glutamine is better for treatment than prevention in exhaustive exercise.

Introduction: Glutamine is known as the richest nonessential amino acid in the human body. The intake of glutamine is not only beneficial to nutrition but also reported to enhance inflammation reducing bioactivity in exercise. Although studies have demonstrated that glutamine is beneficial for exercise, the optimal intake timing remains unclear. This study examined whether the effects of glutamine on tissue damage and physiology differ between intake timings. Methods: Rats were divided into without L-glutamine supplementation (vehicle), with L-glutamine before exhaustive exercise (prevention), and with L-glutamine after exhaustive exercise (treatment) groups. Exhaustive exercise was induced by treadmill running and L-glutamine was given by oral feeding. The exhaustive exercise began at a speed of 10 miles/min and increased in increments of 1 mile/min, to a maximum running speed of 15 miles/min with no incline. The blood samples were collected before exhaustive exercise, 12 h and 24 h after exercise to compare the creatine kinase isozyme MM (CK-MM), red blood cell count and platelet count. The animals were euthanized on 24 h after exercise, and tissue samples were collected for pathological examination and scored the severity of organ injury from 0 to 4. Results: The CK-MM was elevated gradually after exercise in the vehicle group; however, CK-MM was decreased after L-glutamine supplementation in the treatment group. The treatment group had higher red blood cell count and platelet count than the vehicle and prevention group after exercise. In addition, the treatment group had less tissue injury in the cardiac muscles, and kidneys than prevention group. Conclusion: The therapeutic effect of L-glutamine after exhaustive exercise was more effective than preventive before exercise.

Clam Extract Decreases Nasal Symptoms and Improves Sleep Quality after Septoturbinoplasty.

Context: Nasal septal deviation (NSD) causes nasal blockage, which results in lower sleep quality among patients. A high percentage of patients still suffer from nasal symptoms as a result of the inflammatory response that occurs with septoturbinoplasty. Freshwater clams are a common food with an anti-inflammatory effect and have been used for promoting liver function for patients in China. Objectives: The study intended to evaluate the effects of clam extract (CE) in reducing inflammatory response, alleviating nasal blockage, and improving sleep quality for NSD patients after septoturbinoplasty. Design: The study was a randomized, controlled pilot that used a prospective design. Setting: The study took place at the Cheng Hsin General Hospital in Taipei, Taiwan. Participants: Participants were 52 patients with NSD at a clinic at the hospital. Intervention: Patients were randomly assigned to 2 groups: (1) an intervention group that received CE capsules and (2) a control group that received empty capsules that were identical in appearance to the CE capsules. Participants received the treatments 3 times a day for 2 weeks after septoturbinoplasty. Outcome Measures: Participants were assessed for nasal-symptom severity, wound inflammation, serum concentration of tumor necrosis factor alpha (TNF-α), and sleep quality. All outcome measures were undertaken at baseline, on various days during the study depending on the measure, and postintervention on day 14 for wound assessment and sleep quality. Results: After the septoturbinoplasty, the intervention group had lower nasal-symptom severity, wound inflammatory response, TNF-α concentration, and sleep disruption than those in the control group (P < .05). Conclusions: After septoturbinoplasty, CE can reduce nasal-symptom severity and inflammatory response and also improve patients' sleep quality. The anti-inflammatory effects of CE indicate that it can be considered to be an adjuvant therapy to improve sleep quality after surgery.

Stromal-vascular fraction and adipose-derived stem cell therapies improve cartilage regeneration in osteoarthritis-induced rats.

This study aimed to evaluate the effects of the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) on cartilage injury in an osteoarthritis (OA) rat model. Sodium iodoacetate (3 mg/50 µL) was used to induce OA in the left knee joint of rats. On day 14 after OA induction, 50 µL of SVF (5 × 106cells), ADSCs (1 × 106 cells), or 0.9% normal saline (NS) was injected into the left knee-joint cavity of each group. The macroscopic view and histological sections revealed that the articular cartilage in the NS group was damaged, inflamed, uneven and thin, and had hyperchromatic cell infiltration. Notably, the cartilage surface had recovered to nearly normal and appeared smooth and bright on day 14 in the SVF and ADSC groups. Additionally, the white blood cell counts in the SVF and ADSC groups were higher than those in the NS group on day 14. Plasma IL-1ß levels on days 7 and 14 were reduced in the SVF and ADSC groups. These results indicated that both SVF and ADSC treatments may assist in articular cartilage regeneration after cartilage injury. Cell therapy may benefit patients with OA. However, clinical trials with humans are required before the application of SVF and ADSC treatments in patients with OA.

Protective Effect of Calcitriol on Organ Damage Induced by 5-Fluorouracil Treatment.

Chemotherapy is a major therapeutic strategy for patients with cancer. Owing to the severe inflammatory response of chemotherapy, patients experience extreme discomfort during treatment, and this may interrupt treatment completion. The vitamin D3 has a role in anti-inflammation, but no study has explored whether vitamin D3 has beneficial effects on patients undergoing chemotherapy. In this study, we investigated the effect of calcitriol (Vit-D) on inflammatory responses during 5-fluorouracil (5-FU) treatment. Rats were divided into five groups and treated with 1:1 dilution of 5-FU with equal amount of 0.9% saline, 1:3 dilution of 5-FU with 0.9% saline threefold dilution, 5-FU, Vit-D, or 5-FU + Vit-D. A single dose of 15 mg/kg of 5-FU was intravenously administered for 4 h, and the blood biochemical substances and inflammatory cytokines were assessed after the intervention. The 5-FU group had higher AST, ALT, LDH, and CPK levels than those in the 5-FU + Vit-D group. The 5-FU + Vit-D group had a lower TNF-α value than the 5-FU. The IL-6 levels in the 5-FU + Vit-D group were also significantly lower than those in 5-FU. Calcitriol administration during 5-FU therapy can alleviate the production of inflammatory cytokines and liver damage.

Antimicrobial and anti-inflammatory potential of Angelica dahurica and Rheum officinale extract accelerates wound healing in Staphylococcus aureus-infected wounds.

Wound infection is a serious clinical problem, and the most common infection-causing bacteria are Staphylococcus aureus and Pseudomonas aeruginosa. Angelica dahurica and Rheum officinale extract (ARE) was reported to accelerate excisional wound healing in rats. In this study, we investigated the therapeutic effects of ARE on bacterial-infected wounds. Thirty Sprague-Dawley rats were divided into three groups: normal saline (NS), ARE, and biomycin ointment (BO). Full-thickness dorsal excisions in all the rats were infected with 108 colony-forming units of S. aureus; the treatments were applied once daily for 7 days. Results showed that the residual wound area in ARE group was smaller than those in NS and BO groups. TBCs on wound sites gradually decreased in ARE and BO groups. The body temperature and plasma inflammatory cytokines (TNF-α, IL-6) levels increased after bacterial infection at 24 h in all groups. After treatment, BT and inflammatory cytokines levels decreased in ARE group. Histological observations showed ARE group exhibited earlier scab formation, denser dermal granulation tissue, thicker epidermis, and more angiogenesis markers than the other groups. In conclusion, ARE accelerated wound healing in S. aureus-infected wounds. We proposed ARE exhibited potential antimicrobial and anti-inflammatory effects and stimulated angiogenesis, thus improving healing in infected wounds.

Effective Treatment of Bovine Mastitis with Intramammary Infusion of Angelica dahurica and Rheum officinale Extracts.

Mastitis in dairy cattle is a highly prevalent infectious disease, causing considerable economic loss worldwide. In this study, we used Angelica dahurica and Rheum officinale extracts (designated as Yi-Xiong-Tang, YXT) for mastitis treatment. California mastitis test (CMT) was performed and 67 mastitis udder quarters were identified among 179 lactating dairy cows. These 67 mastitis udder quarters were subjected to treatments by intramammary infusion of YXT twice a day for three consecutive days. The mastitis indicators including clots, lactate dehydrogenase (LDH), TNF-α, IL-6, IL-8, and total viable count of bacteria (TVC) in milk were examined before and after the YXT treatment to evaluate its effectiveness. Levels of mastitis indicators from mastitis udder quarters were elevated. After YXT treatment, normal levels of these indicators were restored: TVC, 2.10 × 104 - 9.20 × 106 CFU/mL; clots, 6.56 ± 0.43 mg/mL; LDH, 181.0 ± 18.55 U/L; TNF-α, 0.02 ± 0.02 ng/mL; IL-6, 41.4 ± 11.46 pg/mL; and IL-8, 1.85 ± 0.60 pg/mL. Compared with the antibiotic therapy, YXT treatment has a shorter treatment course and might have lower probability for the causative agents to develop drug resistance because YXT is in fact a cocktail containing multiple active ingredients.

Heat adaptation from regular hot water immersion decreases proinflammatory responses, HSP70 expression, and physical heat stress.

Hot-water immersion (HWI) is a type of thermal therapy for treating various diseases. In our study, the physiological responses to occasional and regular HWI have been explored. The rats were divided into a control group, occasional group (1D), and regular group (7D). The 1D and 7D groups received 42°C during 15mins HWI for 1 and 7 days, respectively. The blood samples were collected for proinflammatory cytokines examinations, the heart, liver and kidney were excised for subsequent IHC analysis to measure the level of heat shock protein 70 (HSP70). The results revealed that the body temperature increased significantly during HWI on Day 3 and significantly declined on Days 6 and 7. For the 7D group, body weight, heart rate, hematocrit, platelet, osmolarity, and lactate level were lower than those in the 1D group. Furthermore, the levels of granulocyte counts, tumor necrosis factor-α, and interleukin-6 were lower in the 7D group than in the 1D group. The induction of HSP70 in the 1D group was higher than in the other groups. Physiological responses to occasional HWI are disadvantageous because of heat stress. However, adaptation to heat from regular HWI resulted in decreased proinflammatory responses and physical heat stress.

Effects of Angelica dahurica and Rheum officinale Extracts on Excisional Wound Healing in Rats.

The main objective of wound treatments is to restore the functional skin properties and prevent infection. Traditional Chinese medicine provides alternative anti-inflammatory, antimicrobial, and wound healing therapies. Both Angelica dahurica extract (AE) and Rheum officinale extract (RE) possess antimicrobial activity. In this study, AE and RE were applied in wound treatment to investigate their healing effects. Thirty Sprague-Dawley rats with dorsal full-thickness skin excision were divided into normal saline (NS), AE, RE, AE plus RE (ARE), and Biomycin (BM) groups. The treatment and area measurement of wounds were applied daily for 21 days. Wound biopsies and blood samples were obtained for histology examinations and cytokine analysis. Results showed that wound contraction in ARE group was significantly higher than that in NS and BM groups (P < 0.05). Histological analysis showed that more inflammatory cell infiltration, collagen fibers, and myofibroblasts were observed in ARE treated group than those in NS group on days 3-5. In ARE group, plasma IL-6 levels were elevated during days 3-5 (P > 0.05), and plasma TGF-ß1 levels were significantly lower than those in the NS group on days 3-4 (P < 0.05). In conclusion, ARE accelerates wound healing during inflammation and proliferation phases.

The inhibitory effect of 7,7″-dimethoxyagastisflavone on the metastasis of melanoma cells via the suppression of F-actin polymerization.

7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus × media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2). Moreover, DMGF did not influence tube formation but inhibited the migration of endothelial cells. Furthermore, animal models were used to monitor the effects of DMGF on tumor metastasis, and all models showed that DMGF significantly suppressed the metastatic behaviors of B16F10 cells, including intravasation, colonization, and invasion of the lymphatic duct. In addition, DMGF could also reduce the densities of the blood vessels in the tumor area in vivo. Further investigation of the molecular mechanisms of anti-metastatic activity revealed that DMGF can down-regulate the levels of key modulators of the Cdc42/Rac1 pathway to interfere in F-actin polymerization and suppress the formation of lamellipodia by reducing the phosphorylation of CREB. These data suggested that DMGF presents anti-metastatic activities in B16F10 melanoma cells. Here, we demonstrated that DMGF can inhibit the metastasis of highly invasive melanoma cancer cells through the down-regulation of F-actin polymerization. Considering these findings, DMGF may be further developed to serve as a chemoprevention drug for patients with metastatic melanoma.

Prophylactic acetylsalicylic acid attenuates the inflammatory response but fails to protect exercise-induced liver damage in exercised rats.

This study evaluated the effects of acetylsalicylic acid (ASA) on exercise-induced inflammatory response, muscle damage, and liver injury in rats. Wistar-Kyoto (WKY) rats were divided into six groups: control (C), exercise (E), C+20mg ASA, E+20mg ASA, C+100mg/kg ASA, and E+100mg ASA groups. ASA or a vehicle was orally administered through gavage 1h before a treadmill test. Upon trial completion, blood was drawn at 1, 12, and 24h for biochemical analysis, and livers were excised at 24h for a histological assessment. Our results revealed that 100mg/kg ASA significantly reduced interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in the E groups; however, the IL-10 level was considerably increased. Moreover, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and histological hepatic damage increased significantly in the E+100mg ASA group compared with the corresponding changes in the E group. These results suggest that the prophylactic administration of particularly high-dose ASA alleviates exercise-induced inflammatory response but exacerbates liver injury.

Vitamin D3 Reduces Tissue Damage and Oxidative Stress Caused by Exhaustive Exercise.

Exhaustive exercise results in inflammation and oxidative stress, which can damage tissue. Previous studies have shown that vitamin D has both anti-inflammatory and antiperoxidative activity. Therefore, we aimed to test if vitamin D could reduce the damage caused by exhaustive exercise. Rats were randomized to one of four groups: control, vitamin D, exercise, and vitamin D+exercise. Exercised rats received an intravenous injection of vitamin D (1 ng/mL) or normal saline after exhaustive exercise. Blood pressure, heart rate, and blood samples were collected for biochemical testing. Histological examination and immunohistochemical (IHC) analyses were performed on lungs and kidneys after the animals were sacrificed. In comparison to the exercise group, blood markers of skeletal muscle damage, creatine kinase and lactate dehydrogenase, were significantly (P < 0.05) lower in the vitamin D+exercise group. The exercise group also had more severe tissue injury scores in the lungs (average of 2.4 ± 0.71) and kidneys (average of 3.3 ± 0.6) than the vitamin D-treated exercise group did (1.08 ± 0.57 and 1.16 ± 0.55). IHC staining showed that vitamin D reduced the oxidative product 4-Hydroxynonenal in exercised animals from 20.6% to 13.8% in the lungs and from 29.4% to 16.7% in the kidneys. In summary, postexercise intravenous injection of vitamin D can reduce the peroxidation induced by exhaustive exercise and ameliorate tissue damage, particularly in the kidneys and lungs.

Aliskiren ameliorates chlorhexidine digluconate-induced peritoneal fibrosis in rats.

BACKGROUND: Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of aliskiren on chlorhexidine digluconate-induced PF in rats. MATERIALS AND METHODS: The PF was induced in Sprague-Dawley rats by daily administration of 0.5 mL 0.1% chlorhexidine digluconate in normal saline via PD tube for 1 week. Rats received daily intravenous injections of low-dose aliskiren (1 mg kg(-1)) or high-dose aliskiren (10 mg kg(-1)) for 1 week. After 7 days, conventional 4.25% Dianeal (30 mL) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. RESULTS: There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D(4)/P(4) urea level was reduced, the D(4)/D(0) glucose level, serum and dialysate transforming growth factor-beta1 (TGF-beta1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PS group compared with the vehicle group. Aliskiren decreased the serum and dialysate TGF-beta1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-beta1, alpha-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. Moreover, high-dose aliskiren had better protective effects against PF than low dose in rats. CONCLUSIONS: Aliskiren protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-beta1 production.

Bio-inspired arene cis-dihydroxylation by a non-haem iron catalyst modeling the action of naphthalene dioxygenase.

Reported in this paper is the first example of a biomimetic iron complex, ([Fe(II)(TPA)(NCMe)(2)](2+) (TPA = tris(2-pyridylmethyl)amine), that catalyses the cis-dihydroxylation of an aromatic double bond, mimicking the action of the non-haem iron enzyme naphthalene dioxygenase and shedding light on its possible mechanism of action.

Targeting the tumor-associated folate receptor with an 111In-DTPA conjugate of pteroic acid.

The cell membrane folate receptor is a potential molecular target for tumor-selective drug delivery. To probe structural requirements for folate receptor targeting with low molecular weight radiometal chelates, specifically the role of the amino acid fragment of folic acid (pteroylglutamic acid) in mediating targeting selectivity, the amide-linked conjugate pteroyl-NHCH(2)CH(2)OCH(2)CH(2)OCH(2)CH(2)NH-DTPA was prepared by a three-step procedure from pteroic acid, 2,2'-(ethylenedioxy)-bis(ethylamine), and t-Bu-protected DTPA. This conjugate, 1-{2-[2-[(2-(biscarboxymethyl-amino)ethyl)-carboxymethyl-amino]ethyl]-carboxymethyl-amino}-acetylamino-3,6-dioxa-8-pteroylamino-octane (1), was employed for synthesis of the corresponding (111)In(III) radiopharmaceutical. Following intravenous administration to athymic mice, the (111)In complex of 1 was found to selectively localize in folate receptor-positive human KB tumor xenografts and to afford prolonged tumor retention of the (111)In radiolabel (5.4 +/- 0.8, 5.6 +/- 1.1, and 3.6 +/- 0.6% of the injected dose per gram of tumor at 1, 4, and 24 h, respectively). The observed tumor localization was effectively blocked by co-administration of folic acid with the (111)In-1 complex, consistent with a folate receptor-mediated targeting process. In control studies, tumor targeting with this pteroic acid conjugate appears as effective as that seen using (111)In-DTPA-folate, a radiopharmaceutical that has progressed to clinical trials for detection of folate receptor-expressing gynecological tumors.

Folate-receptor-targeted radionuclide imaging agents.

The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including delivery of radiolabeled folate-chelate conjugates for diagnostic imaging. This review surveys the growing literature on tumor imaging with radionuclide agents targeted to the folate receptor. Successful folate-receptor targeting has been reported, both in vitro and in vivo, using a variety of radionuclides that are suitable for clinical diagnostic imaging (67Ga, 111In, 99mTc, 66Ga, and 64Cu). While none of these agents has, to date, been demonstrated to have clinical efficacy as a diagnostic tool, existing data indicates that it is feasible to noninvasively assess (at least qualitatively) tissue folate receptor levels by external radionuclide imaging.

The folate receptor as a molecular target for tumor-selective radionuclide delivery.

The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including radiolabeled folate-chelate conjugates for diagnostic imaging. We review here some background on the folate receptor as tumor-associated molecular target for drug delivery, and briefly survey the literature on tumor-targeting with radiolabeled folate-chelate conjugates.