Background: The chronic pain can disturb physical, psychological, and social performances. Analgesic agents are widely used but some antidepressants (ADs) showed analgesia also. Bupropion is using for smoke cessation but it can change morphine withdrawal signs such as pain. This study tested the acute systemic effect of bupropion on formalin induced pain behavior in rats. Methods: Wistar male healthy rats were divided into 7 groups (control, sham, and 5 treated groups with 10, 30, 90, 120, and 200 mg/kg of bupropion, i.p.). The bupropion injected 3 hours prior to formalin induced pain behavior. Formalin (50 ${\mu}l$, 2.5%) was injected subcutaneously in dorsal region of right hindpaw in all animals. Nociceptive signs were observed continuously on-line and off-line each minute. Common pain scoring was used for pain assessment. Results: The analysis of data by one-way ANOVA showed that bupropion can reduce pain scores in the second phase but not in first phase. Bupropion decreased the licking/biting duration significantly in first and second phase of formalin test. Conclusions: The results showed that bupropion has analgesic effects at systemic application. The change of second phase of the pain behavior was significant and it revealed that central mechanisms involve in bupropion analgesia.
Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases.
In perennial ginseng plantations, the effective control of various diseases is one of the most critical factors for increasing yields. Enhancing the resistance to disease through induced systemic resistance (ISR) and anti-microbial activity of beneficial soil bacteria, is currently considered to be a potential promising approach to integrate pathogen management for sustainable agriculture. However, the effective in vitro culture systems for testing ISR in ginseng plants have been rarely reported. In this study, I have successfully developed an in vitro germ-free culture system of Panax ginseng seedling for diverse purposes. With this useful system, we also tested BTH-induced priming effects against Botrytis cinerea and Colletotrichum panacicola. Compared to the drain method for enhancing ISR effects to ginseng seedlings, the direct method of spraying leaves somewhat increased the defense activity to these major fungal pathogens. Consistently, the expression of pathogen related PgPR10 and PgCAT were greatly and rapidly enhanced in the BTH-treated ginseng seedlings by treatment with C. panacicola. Our results revealed that the in vitro culture system can be used for developing eco-friendly and versatile bio-control agents for harmful diseases in ginseng cultivation.
Objectives: This study examined the safety of tattoo ink by analyzing the phenol contents in tattoo inks and its risk assessment of selected phenol. Methods: A sample of 30 tattoo inks was purchased, the phenol contents were analyzed, and a risk assessment on dermal exposure from tattooing was carried out. Hazard identification was collected from toxicity data on systemic effects caused by dermal exposure to phenol, and the most sensitive toxicity value was adopted. Exposure assessment ($Exposure_{phenol}$) was calculated by applying phenol contents and standard exposure factors, while dose-response assessment was based on the collected toxicity data and skin absorption rate of phenol, assessment factors (AFs) for derived no-effect level ($DNEL_{demal}$). In addition, the risk characterization was calculated by comparing the risk characterization ratio (RCR) with $Exposure_{phenol}$ and $DNEL_{dermal}$ Results: The phenol concentration in the 30 products was from 1.4 to $649.1{\mu}g/g$. The toxicity value for systemic effects of phenol was adopted at 107 mg/kg. $Exposure_{phenol}$ in tattooing was from 0.000087 to 0.040442 mg/kg. $DNEL_{dermal}$ was calculated at 0.0072 mg/kg (=toxicity value 107 mg/kg ${\div}$ AFs 650 ${\times}$ skin absorption rate 4.4%). Thirteen out of 30 products showed an RCR between 1.02 and 5.62. The RCR of all red inks was above 1. Conclusions: Phenol was detected in all of the 30 tattoo inks, and the RCR of 13 products above 1 indicates a high level of risk concern, making it necessary to prepare safety management standards for phenol in tattoo inks.
Purpose: This study evaluated the systemic and local effects of doxycycline (DOX) and low-intensity laser (LIL) treatment as adjuvants to scaling and root planing (SRP) in the treatment of experimental periodontitis in rats. Methods: The sample consisted of 180 male rats (Rattus norvegicus albinus, Wistar), of which 30 did not receive induction of periodontal disease (negative control [NC] group) and 150 received induction of periodontal disease in the lower first molar. After 7 days, the ligature was removed, and the animals were divided into the following groups: NT (no treatment), SRP (SRP), DOX (SRP and DOX irrigation), LIL (SRP and laser irradiation), and DOX+LIL (SRP, DOX, and LIL). The animals were euthanized at 7, 15, and 30 days; thereafter, biochemical, radiographic, histological, and immunohistochemical analyses were performed. Results: In the intragroup analysis, lower concentrations of α-1-glycoprotein acid (α-1-Ga) and complement 3 (C3) were observed in the DOX+LIL group than in all other groups at all time points, as well as lower levels of complement 4 (C4) at 15 and 30 days (P<0.001). Less bone loss was observed in the DOX, LIL, and DOX+LIL groups than in the NC and SRP groups at all time points (P<0.001). There was a smaller number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the DOX+LIL group than in the other groups at all time points (P<0.001). Positive correlations were observed between the systemic levels of α-1-Ga, C3, and C4 and the number of TRAP-positive cells. Conclusions: The combination of DOX with LIL as SRP adjuvants was effective both systemically and locally for the treatment of experimental periodontitis in rats.
Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.
Background: This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic breast cancer as first or second line chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with breast cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In first line pemetrexed based regimens, 10 clinical studies which including 513 patients with advanced breast cancer were considered eligible for inclusion. For second line pemetrexed based chemotherapy, 5 clinical studies which including 281 patients with advanced breast cancer were considered eligible. Systemic analysis suggested that, in all patients, pooled RR was 32.6% (167/513) in pemetrexed based first line regimens, and 13.9 % (39/281) in pemetrexed based second line regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia in pemetrexed based first line treatment; and lymphopenia, neutropenia, leukopenia, as well as anemia in second line chemotherapy. One treatment related death occurred with pemetrexed based second line treatment. Conclusion: This systemic analysis suggests that pemetrexed based first line regimens are associated with a reasonable response rate and acceptable toxicity, however with low response rate for treating patients with metastatic breast cancer when is used in the second line.
Background: The multitude of the therapeutic usefulness of intra-articular injection of hyaluronate on oateoarthritis of the knee is still in question. The objective of this systemic review was to elucidate both the therapeutic efficacy and the safety of intra-articular administration of hyaluronic acid for degenerative osteoarthritis of the knee joints. Methods: I searched MEDLINE and Korea Medical Database (KMbase) from January 1990 to April 2007 using a combination search terms for knee osteoarthritis and hyaluronic acid and a filter for randomized controlled trials. I extracted data on pain at rest, and during or just after movement, on joint function, and on adverse events. Results: Ten trials that reported usable quantitative information on any of the predefined end points were identified and included in the systemic review. Intra-articular injection of hyaluronic acid can decrease symptoms of osteoarthritis of the knee. The study revealed significant improvements in pain and functional outcomes with few adverse effects. However, there was significant between-study heterogeneity in the estimates of the efficacy of hyaluronic acid. Sub-group analysis showed that lower methodological quality such as a single-blind or single-center design resulted in higher estimates hyaluronic acid efficacy, and that patients older than sixty years of age and those with the most advanced radiographic stage of osteoarthritis were less likely to benefit from intra-articular injection of hyaluronic acid. Conclusion: According to the currently available evidence, intra-articular hyaluronic acid has been proven clinically effective for the patients bearing the knee osteoarthritis with NSAID-induced GI troubles or inapplicable to any surgery, and may be associated with lower risk of adverse events.
Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers ($IL-1{\alpha}$, $IL-1{\beta}$, IL-8 and $TNF-{\alpha}$) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.
Periodontal inflammation increases the risk of tooth loss, particularly in cases where there is an associated loss of alveolar bone and periodontal ligament (PDL). Histological and morphometric evaluation of periodontal inflammation is difficult. Especially, the lengths of the periodontal ligament and interdental alveolar bone space have not been quantified. A quantitative imaging procedure applicable to an animal model would be an important clinical study. The purpose of this study was to quantify the loss of alveolar bone and periodontal ligament by evaluation with micro-computed tomography (micro-CT). Another purpose was to investigate differences in infections with systemic E. coli LPS and TNF-${\alpha}$ on E. coli lipopolysaccharide (LPS) in loss of alveolar bone and periodontal ligament model on mice. This study showed that linear measurements of alveolar bone loss were represented with an increasing trend of the periodontal ligament length and interdental alveolar process space. The effects of systemic E. coli LPS and TNF-${\alpha}$ on an E. coli LPS-induced periodontitis mice model were investigated in this research. Loss of periodontal ligament and alveolar bone were evaluated by micro-computed tomography (micro-CT) and calculated by the two- and three dimensional microstructure morphometric parameters. Also, there was a significantly increasing trend of the interdental alveolar process space in E. coli LPS and TNF-${\alpha}$ on E. coli LPS compared to PBS. And E. coli LPS and TNF-${\alpha}$ on E. coli LPS had a slightly increasing trend of the periodontal ligament length. The increasing trend of TNF-${\alpha}$ on the LPS-induced mice model in this experiment supports the previous studies on the contribution of periodontal diseases in the pathogenesis of systemic diseases. Also, our findings offer a unique model for the study of the role of LPS-induced TNF-${\alpha}$ in systemic and chronic local inflammatory processes and inflammatory diseases. In this study, we performed rapidly quantification of the periodontal inflammatory processes and periodontal bone loss using micro-computed tomography (micro-CT) in mice.
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