OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neur...OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.展开更多
Background: Breast cancer remains an important medical challenge, despite sustained global efforts at its prevention and control. Various immunological factors are expressed in the serum during breast tumourigenesis, ...Background: Breast cancer remains an important medical challenge, despite sustained global efforts at its prevention and control. Various immunological factors are expressed in the serum during breast tumourigenesis, and can be of value in the surveillance of the disease. These serum bio-markers include pro-inflammatory cytokines since breast cancer is associated with chronic inflammation. In our locality with different racial/ethnic variations from Caucasian as well as environmental factors, there is scanty information on the value of these serum factors in screening and surveillance of breast cancer—hence the need for this study. Methodology: A total of 68 females (mean age = 48.7 ± 8.7 yrs) with clinically and pathologically confirmed breast cancer were recruited by self selection;representing breast cancer patients group. Due to small sample size they were further grouped into advanced stage breast cancer cases (N = 40) and early stage breast cancer cases (N = 28). Controls consisted of two groups: A—Patient control group (N = 21) comprised females with benign breast tumour (15 cases with fibroadenoma and 6 cases with fibrocystic disease) and group B—apparently healthy age/sex matched control group (N = 21). Pre-treatment samples were collected after which all patients underwent standard treatment modalities (neoadjuvant or adjuvant chemotherapy, radiotherapy, chemoradiation, and/or surgery;depending on the stage of presentation and thereafter post treatment samples were collected after 3 and 6 months respectively. Serum from the patients and controls were assayed immunoenzymatically for TNF-α and IL-1. Results: The results showed that at 6 months post-treatment stage, the mean values of IL-1 differed significantly (P > 0.05) when advanced stage breast cancer were compared with early stage and apparently healthy control groups respectively. Likewise at 6 months post-treatment stage, the TNF-α mean values differed significantly (P > 0.05) between advanced stage breast cancer and apparently healthy control. No significant differences in mean values were recorded across disease and treatment groups in both IL-1 and TNF-α at pre-treatment and 3 months post-treatment stages. Majority of the breast cancer patients studied were married (91%) and had children, of low income, never smoke cigarette, diagnosed at age above 46 years and presented at advanced stages of the disease. Results also showed that 78% of the cases did not have any history of cancer in their families. Also, 63% of the cases had body mass index values suggestive of obesity (>30 kg/m2). Conclusion: Results suggest that the use of serum levels of TNF-α and IL-1 in the diagnosis of breast cancer in our racial/ethnic environment is of limited clinical value. However it could be useful in disease surveillance in metastasis and relapse. Based on our findings, it could also be concluded that cigarette smoking and social sophistication are not among the risk factors to cancer in this part of the world, contrary to the situation in the advanced parts of the world.展开更多
文摘OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.
文摘Background: Breast cancer remains an important medical challenge, despite sustained global efforts at its prevention and control. Various immunological factors are expressed in the serum during breast tumourigenesis, and can be of value in the surveillance of the disease. These serum bio-markers include pro-inflammatory cytokines since breast cancer is associated with chronic inflammation. In our locality with different racial/ethnic variations from Caucasian as well as environmental factors, there is scanty information on the value of these serum factors in screening and surveillance of breast cancer—hence the need for this study. Methodology: A total of 68 females (mean age = 48.7 ± 8.7 yrs) with clinically and pathologically confirmed breast cancer were recruited by self selection;representing breast cancer patients group. Due to small sample size they were further grouped into advanced stage breast cancer cases (N = 40) and early stage breast cancer cases (N = 28). Controls consisted of two groups: A—Patient control group (N = 21) comprised females with benign breast tumour (15 cases with fibroadenoma and 6 cases with fibrocystic disease) and group B—apparently healthy age/sex matched control group (N = 21). Pre-treatment samples were collected after which all patients underwent standard treatment modalities (neoadjuvant or adjuvant chemotherapy, radiotherapy, chemoradiation, and/or surgery;depending on the stage of presentation and thereafter post treatment samples were collected after 3 and 6 months respectively. Serum from the patients and controls were assayed immunoenzymatically for TNF-α and IL-1. Results: The results showed that at 6 months post-treatment stage, the mean values of IL-1 differed significantly (P > 0.05) when advanced stage breast cancer were compared with early stage and apparently healthy control groups respectively. Likewise at 6 months post-treatment stage, the TNF-α mean values differed significantly (P > 0.05) between advanced stage breast cancer and apparently healthy control. No significant differences in mean values were recorded across disease and treatment groups in both IL-1 and TNF-α at pre-treatment and 3 months post-treatment stages. Majority of the breast cancer patients studied were married (91%) and had children, of low income, never smoke cigarette, diagnosed at age above 46 years and presented at advanced stages of the disease. Results also showed that 78% of the cases did not have any history of cancer in their families. Also, 63% of the cases had body mass index values suggestive of obesity (>30 kg/m2). Conclusion: Results suggest that the use of serum levels of TNF-α and IL-1 in the diagnosis of breast cancer in our racial/ethnic environment is of limited clinical value. However it could be useful in disease surveillance in metastasis and relapse. Based on our findings, it could also be concluded that cigarette smoking and social sophistication are not among the risk factors to cancer in this part of the world, contrary to the situation in the advanced parts of the world.
