No information is available regarding the utilization of iron (Fe) from different Fe sources at a targettissue level. To detect differences in Fe metabolic utilization among Fe sources, the effect of intravenouslyinje...No information is available regarding the utilization of iron (Fe) from different Fe sources at a targettissue level. To detect differences in Fe metabolic utilization among Fe sources, the effect of intravenouslyinjected Fe on growth performance, hematological indices, tissue Fe concentrations and Fe-containingenzyme activities and gene expressions of Fe-containing enzymes or protein in broilers was investigated.On d 22 post-hatching, a total of 432 male chickens were randomly allotted to 1 of 9 treatments ina completely randomized design. Chickens were injected with either a 0.9% (wt/vol) NaCl solution(control) or a 0.9% NaCl solution supplemented with Fe sulphate or 1 of 3 organic Fe sources. The 3organic Fe sources were Fe chelates with weak (Fe-MetW), moderate (Fe-ProtM) or extremely strong (Fe-ProtES) chelation strength. The 2 Fe dosages were calculated according to the Fe absorbabilities of 10%and 20% every 2 d for a duration of 20 d. Iron injection did not affect (P > 0.05) ADFI, ADG or FCR duringeither 1 to 10 d or 11 to 20 d after injections. Hematocrit and Fe concentrations in the liver and kidney ond 10 after Fe injections, and Fe concentrations in the liver or pancreas and ferritin heavy-chain (FTH1)protein expression level in the liver or spleen on d 20 after Fe injections increased (P≤0.05) as injectedFe dosages increased. When the injected Fe level was high at 20% Fe absorbability, the chickens injectedwith Fe-ProtES had lower (P < 0.001) liver or kidney Fe concentrations and spleen FTH1 protein levelsthan those injected with Fe-MetW or Fe-ProtM on d 20 after injections. And they had lower (P < 0.05)liver cytochrome C oxidase mRNA levels on d 20 after injections than those injected with Fe-MetW or Fesulphate. The results from this study indicate that intravenously injected Fe from Fe-ProtES was the least utilizable and functioned in the sensitive target tissue less effectively than Fe from Fe sulfate, Fe-MetW or Fe-ProtM.展开更多
BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use o...BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.展开更多
Over the years, it was getting attention to hepatitis C virus (HCV) and human immu-nodeficiency virus (HIV) infection among injected drug users (IDUs) in Taiwan. This study investigated the frequency of risky behavior...Over the years, it was getting attention to hepatitis C virus (HCV) and human immu-nodeficiency virus (HIV) infection among injected drug users (IDUs) in Taiwan. This study investigated the frequency of risky behaviors for HCV carriers and IDUs who were HIV carriers in methadone maintenance treatment program. The subjects, intravenously injected heroin abusers, were collected from a special methadone maintenance treatment clinic. The survey included characteristics of participants, sexual activity and attitude towards condom usage. The total number of subjects was 151. Data were analyzed using the statistical package SPSS 15.0. The analytical methods included descriptive analysis, Fisher’s exact test, and the logistic regression model. The study showed that 82% of intravenously injected heroin abusers were hepatitis C virus (HCV)-positive, and 44.4% were hepatitis B virus (HBV)-positive;89.5% of HIV-positive heroin abusers were type C hepatitis positive. Only 21.2% of these intra-venously injected heroin abusers always used a condom, and 39.7% never used a condom during sexual activity. Logistic regression analysis showed smoking, sharing syringes needles, HBV status and condom use status were four main risk factors on HIV infection. Sharing or using contaminated syringes needles was the main cause of HIV, HBV, and HCV infection in the drug addiction group. Since our government has the policy of providing a methadone maintenance treatment program, the spread of HIV is under control, but knowledge about HIV and safe sex education still needs improvement.展开更多
AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyt...AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyte-like cells. Liver fibrosis in SD rats was induced with carbon tetrachloride. Following hepatocyte induction in vitro, 4',6-diamidino- 2-phenylindole (DAPI)-labeled MSCs were transplanted by intravenous, intrahepatic, and intraperitoneal injection. Histopathological staining, immunohistochemistry, and biochemical analysis were used to compare the morphological and functional liver regeneration among different MSC injection modalities. The expression differences of interleukins, growth factor, extracellular matrix, matrix metalloproteinases, and tissue inhibitor of metalloproteinase were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) andenzyme linked immunosorbent assay (ELISA). RESULTS: Four days after exposure to hepatocyte differentiation medium, MSCs that did not express hepatocyte markers could express α-fetoprotein, albumin, and cytokeratin 18. The results of histopathological staining, immunohistochemistry, and biochemical analysis indicated that intravenous injection is more effective at rescuing liver failure than other injection modalities. DAPI-labeled cells were found around liver lobules in all three injection site groups, but the intravenous group had the highest number of cells. PCR and ELISA analysis indicated that interleukin-10 (IL-10) was highest in the intravenous group, whereas il1β, il6, tnfα and tgfβ, which can be regulated by IL10 and are promoters of liver fibrosis, were significantly lower than in the other groups. CONCLUSION: MSC administration is able to protect against liver fibrosis. Intravenous injection is the most favorable treatment modality through promotion of IL10 expression.展开更多
AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of colitis.METHODS:MSCs were isolated from C57BL/6 mouse adipose tissue.MSC c...AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of colitis.METHODS:MSCs were isolated from C57BL/6 mouse adipose tissue.MSC cultures were analyzed according to morphology,cellular differentiation potential,and surface molecular markers.Experimental acute colitis was induced in C57BL/6 mice by oral administration of2%dextran sulfate sodium(DSS)in drinking water ad libitum from days 0 to 7.Colitis mice were treated with1×106 MSCs via intraperitoneal or intravenous injection on days 2 and 5.The disease activity index was determined daily based on the following parameters:weight loss,stool consistency and presence of blood in the feces and anus.To compare morphological and functional differences in tissue regeneration between different MSC injection modalities,mice were euthanized on day 8,and their colons were examined for length,weight,and histopathological changes.Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit.Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated d UDPbiotin nick end labeling assay.RESULTS:Intravenous infusion of MSCs was more effective than intraperitoneal treatment(P<0.001)in reducing the clinical and histopathologic severity of colitis,which includes weight loss,diarrhea and inflammation.An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells.This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)];and by the up-regulation of anti-inflammatory cytokines(IL-10 and IL-4).Intravenous transplantation alsoinduced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs,which did not occur with intraperitoneal transplantation(P=0.006).An increase in apoptotic T cells was observed after intravenous,but not intraperitoneal,MSC infusion,suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation(P=0.027).CONCLUSION:Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.展开更多
AIM:To investigate the therapeutic efficacy of short- term, multiple daily dosing of intravenous interferon (IFN) in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS:IFN-β was intrave...AIM:To investigate the therapeutic efficacy of short- term, multiple daily dosing of intravenous interferon (IFN) in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS:IFN-β was intravenously administered at a total dose of 102 million international units (MIU) over a period of 28 d in 26 patients positive for HBeAg and HBV-DNA. IFN-beta was administered at doses of 2 MIU and 1 MIU on d 1, 3 MIU twice daily from d 2 to d 7, and 1 MIU thrice daily from d 8 to d 28. Patients were followed up for 24 wk after the end of treatment. RESULTS:Six months after the end of the treatment, loss of HBV-DNA occurred in 13 (50.0%) of the 26 patients, loss of HBeAg in 9 (34.6%), development of anti-HBe in 10 (38.5%), HBeAg seroconversion in 8 (30.8%), and normalization of alanine aminotransferase (ALT) levels in 11 (42.0%). CONCLUSION:This 4-wk long IFN-β therapy, which was much shorter than conventional therapy lasting 12 wk or even more than 1 year, produced therapeutic effects similar to those achieved by IFN-α or pegylated- IFN-α (peg-IFN). Fewer adverse effects, greater efficacy, and a shorter treatment period led to an improvement in patients’ quality of life. IFN-β is administered intravenously, whereas IFN-α is administered intramuscularly or subcutaneously. Because both interferons are known to bind to an identical receptor and exert antiviral effects through intracellular signal transduction, the excellent results of IFN-β found in this study may be attributed to the multiple doses allowed by the intravenous route.展开更多
BACKGROUND Detergent poisoning mostly occurs through oral ingestion(>85%),ocular exposure(<15%),or dermal exposure(<8%).Reports of detergent poisoning through an intravenous injection are extremely rare.In ad...BACKGROUND Detergent poisoning mostly occurs through oral ingestion(>85%),ocular exposure(<15%),or dermal exposure(<8%).Reports of detergent poisoning through an intravenous injection are extremely rare.In addition,there are very few cases of renal toxicity directly caused by detergents.Here,we report a unique case of acute kidney injury caused by detergent poisoning through an accidental intravenous injection.CASE SUMMARY A 61-year-old man was intravenously injected with 20 mL of detergent by another patient in the same room of a local hospital.The surfactant and calcium carbonate accounted for the largest proportion of the detergent.The patient complained of vascular pain,chest discomfort,and nausea,and was transferred to our institution.After hospitalization,the patient’s serum creatinine level increased to 5.42 mg/dL,and his daily urine output decreased to approximately 300 mL.Renal biopsy findings noted that the glomeruli were relatively intact;however,diffuse acute tubular injury was observed.Generalized edema was also noted,and the patient underwent a total of four hemodiafiltration sessions.Afterward,the patient’s urine output gradually increased whereas the serum creatinine level decreased.The patient was discharged in a stable status without any sequelae.CONCLUSION Detergents appear to directly cause renal tubular injury by systemic absorption.In treating a patient with detergent poisoning,physicians should be aware that the renal function may also deteriorate.In addition,timely renal replacement therapy may help improve the patient’s prognosis.展开更多
High-performance liquid chromatographic (HPLC) analysis of fluorouracil (5-FU) content of the blood and colon of rabbits is described. There was no marked difference in the plasma 5-FU level and blood concentration ti...High-performance liquid chromatographic (HPLC) analysis of fluorouracil (5-FU) content of the blood and colon of rabbits is described. There was no marked difference in the plasma 5-FU level and blood concentration time curve following intravenous (I. V.) (ear vein) or intraarterial (I.A.) (inferior mesenteric artery) injection of 5-FU 15 mg/kg. However, the distribution of 5-FU in the colon after IA. administration was quite different that after I.V. administration. At 10, 20 and 30 minutes, the 5-FU content in the colon was shown to be 31-, 17- and 14-fold higher with I.A. than with I.V.. Colonic tissue AUCo-480 min. was 2453 and 690 min/mg/ml respectively (p<0.05). It is suggested that to inject 5-FU into selected arteries to treat advanced colorectal cancer may be more useful than I.V. administration.展开更多
Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remai...Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v.and oral routes.展开更多
Graphene oxide(GO)displays promising properties for biomedical applications including drug delivery and cancer therapeutics.However,GO exposure also raises safety concerns such as potential side effects on health.He...Graphene oxide(GO)displays promising properties for biomedical applications including drug delivery and cancer therapeutics.However,GO exposure also raises safety concerns such as potential side effects on health.Here,the biological effects of GO suspended in phosphate buffered saline(PBS)with or without 1% nonionic surfactant Tween 80 were investigated.Based on the ex vivo experiments,Tween 80 significantly affected the interaction between GO and peripheral blood from mice.GO suspension in PBS tended to provoke the aggregation of diluted blood cells,which could be prevented by the addition of Tween 80.After intravenous administration,GO suspension with or without 1% Tween 80 was quickly eliminated by the mononuclear phagocyte system.Nevertheless,GO suspension without Tween 80 showed greater accumulation in lungs than that containing 1% Tween 80.In contrast,less GO was found in livers for GO suspension compared to Tween 80 assisted GO suspension.Organs including hearts,livers,lungs,spleens,kidneys,brains,and testes did not reveal histological alterations.The indexes of peripheral blood showed no change upon GO exposure.Our results together demonstrated that Tween 80 could greatly alter GO's biological performance and determine the pattern of its biodistribution in mice.展开更多
The objective of the study was to compare the concentration of lidocaine in different body fluids/tissues after subarachnoid space and intravenous administrations of a lethal dose of lidocaine.Totally 18 dogs were use...The objective of the study was to compare the concentration of lidocaine in different body fluids/tissues after subarachnoid space and intravenous administrations of a lethal dose of lidocaine.Totally 18 dogs were used in the experiment.Six dogs were given subarachnoid anesthesia,another were given an intravenous injection of a dose of 75 mg/kg weight of lidocaine hydrochloride in 5 min and the last 6 dogs were used as the blank control dogs and given a subarachnoid space injection or a femoral artery injection of the same volume of sodium chloride.As soon as its vital signs disappeared,each dog was dissected and the specimen,such as brain,cerebrospinal fluid(CSF)in lateral ventricle,CSF in subarachnoid space,spinal cord(cervical spinal cord,thoracic spinal cord,lumbar spinal cord,and waist spinal cord),heart,lung,liver,spleen,kidney,bile,urine,heart blood,peripheral blood,muscle in injection location,and muscle in no injection location,were collected for analysis of lidocaine immediately.Analysis was performed with gas chromatography‑mass spectrometry(GC‑MS).From the maximum to the minimum,the order of lidocaine concentration detected in the subarachnoid space‑administered dogs was as follows:CSF in subarachnoid space,waist spinal cord,thoracic spinal cord,CSF in lateral ventricle,lumbar spinal cord,cervical spinal cord,lung,kidney,muscle in injection location,heart,brain,spleen,heart blood,liver,peripheral blood,bile,muscle in no injection location,and urine.The order of lidocaine concentration detected in the intravenously administered dogs was as followed:Kidney,heart,lung,spleen,brain,liver,peripheral blood,bile,heart blood,cervical spinal cord,thoracic spinal cord,muscle in injection location,lumbar spinal cord,muscle in no injection location,CSF in subarachnoid space,urine,and CSF in lateral ventricle.The maximum concentration of lidocaine was detected in the subarachnoid space CSF of subarachnoid space‑administered dead dogs,while in intravenously injected dead dogs,the maximum concentration of lidocaine was detected in the kidney.Our study provides some useful data for the forensic identification of epidural anesthesia accidents to decide the way the lidocaine enters the body.展开更多
基金the National Natural Science Foundation of China(project number 31672440,Beijing,China)the Research Program of State Key Laboratory of Animal Nutrition(project number 2004DA125184G1606,Beijing,China)+1 种基金the Agricultural Science and Technology Innovation Program(ASTIP-IAS09,Beijing,China)the China Agriculture Research System of MOF and MARA(project number CARS-41,Beijing,China).
文摘No information is available regarding the utilization of iron (Fe) from different Fe sources at a targettissue level. To detect differences in Fe metabolic utilization among Fe sources, the effect of intravenouslyinjected Fe on growth performance, hematological indices, tissue Fe concentrations and Fe-containingenzyme activities and gene expressions of Fe-containing enzymes or protein in broilers was investigated.On d 22 post-hatching, a total of 432 male chickens were randomly allotted to 1 of 9 treatments ina completely randomized design. Chickens were injected with either a 0.9% (wt/vol) NaCl solution(control) or a 0.9% NaCl solution supplemented with Fe sulphate or 1 of 3 organic Fe sources. The 3organic Fe sources were Fe chelates with weak (Fe-MetW), moderate (Fe-ProtM) or extremely strong (Fe-ProtES) chelation strength. The 2 Fe dosages were calculated according to the Fe absorbabilities of 10%and 20% every 2 d for a duration of 20 d. Iron injection did not affect (P > 0.05) ADFI, ADG or FCR duringeither 1 to 10 d or 11 to 20 d after injections. Hematocrit and Fe concentrations in the liver and kidney ond 10 after Fe injections, and Fe concentrations in the liver or pancreas and ferritin heavy-chain (FTH1)protein expression level in the liver or spleen on d 20 after Fe injections increased (P≤0.05) as injectedFe dosages increased. When the injected Fe level was high at 20% Fe absorbability, the chickens injectedwith Fe-ProtES had lower (P < 0.001) liver or kidney Fe concentrations and spleen FTH1 protein levelsthan those injected with Fe-MetW or Fe-ProtM on d 20 after injections. And they had lower (P < 0.05)liver cytochrome C oxidase mRNA levels on d 20 after injections than those injected with Fe-MetW or Fesulphate. The results from this study indicate that intravenously injected Fe from Fe-ProtES was the least utilizable and functioned in the sensitive target tissue less effectively than Fe from Fe sulfate, Fe-MetW or Fe-ProtM.
文摘BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.
文摘Over the years, it was getting attention to hepatitis C virus (HCV) and human immu-nodeficiency virus (HIV) infection among injected drug users (IDUs) in Taiwan. This study investigated the frequency of risky behaviors for HCV carriers and IDUs who were HIV carriers in methadone maintenance treatment program. The subjects, intravenously injected heroin abusers, were collected from a special methadone maintenance treatment clinic. The survey included characteristics of participants, sexual activity and attitude towards condom usage. The total number of subjects was 151. Data were analyzed using the statistical package SPSS 15.0. The analytical methods included descriptive analysis, Fisher’s exact test, and the logistic regression model. The study showed that 82% of intravenously injected heroin abusers were hepatitis C virus (HCV)-positive, and 44.4% were hepatitis B virus (HBV)-positive;89.5% of HIV-positive heroin abusers were type C hepatitis positive. Only 21.2% of these intra-venously injected heroin abusers always used a condom, and 39.7% never used a condom during sexual activity. Logistic regression analysis showed smoking, sharing syringes needles, HBV status and condom use status were four main risk factors on HIV infection. Sharing or using contaminated syringes needles was the main cause of HIV, HBV, and HCV infection in the drug addiction group. Since our government has the policy of providing a methadone maintenance treatment program, the spread of HIV is under control, but knowledge about HIV and safe sex education still needs improvement.
基金Supported by Millitary Medicine and Health Foundation of China, No. 08Z030
文摘AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyte-like cells. Liver fibrosis in SD rats was induced with carbon tetrachloride. Following hepatocyte induction in vitro, 4',6-diamidino- 2-phenylindole (DAPI)-labeled MSCs were transplanted by intravenous, intrahepatic, and intraperitoneal injection. Histopathological staining, immunohistochemistry, and biochemical analysis were used to compare the morphological and functional liver regeneration among different MSC injection modalities. The expression differences of interleukins, growth factor, extracellular matrix, matrix metalloproteinases, and tissue inhibitor of metalloproteinase were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) andenzyme linked immunosorbent assay (ELISA). RESULTS: Four days after exposure to hepatocyte differentiation medium, MSCs that did not express hepatocyte markers could express α-fetoprotein, albumin, and cytokeratin 18. The results of histopathological staining, immunohistochemistry, and biochemical analysis indicated that intravenous injection is more effective at rescuing liver failure than other injection modalities. DAPI-labeled cells were found around liver lobules in all three injection site groups, but the intravenous group had the highest number of cells. PCR and ELISA analysis indicated that interleukin-10 (IL-10) was highest in the intravenous group, whereas il1β, il6, tnfα and tgfβ, which can be regulated by IL10 and are promoters of liver fibrosis, were significantly lower than in the other groups. CONCLUSION: MSC administration is able to protect against liver fibrosis. Intravenous injection is the most favorable treatment modality through promotion of IL10 expression.
基金Supported by Fundo de IncentivoàPesquisa e Eventos do Hospital de Clínicas de Porto Alegre and Coordenacao de Aperfeicoamento de Pessoal de Nível Superior
文摘AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of colitis.METHODS:MSCs were isolated from C57BL/6 mouse adipose tissue.MSC cultures were analyzed according to morphology,cellular differentiation potential,and surface molecular markers.Experimental acute colitis was induced in C57BL/6 mice by oral administration of2%dextran sulfate sodium(DSS)in drinking water ad libitum from days 0 to 7.Colitis mice were treated with1×106 MSCs via intraperitoneal or intravenous injection on days 2 and 5.The disease activity index was determined daily based on the following parameters:weight loss,stool consistency and presence of blood in the feces and anus.To compare morphological and functional differences in tissue regeneration between different MSC injection modalities,mice were euthanized on day 8,and their colons were examined for length,weight,and histopathological changes.Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit.Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated d UDPbiotin nick end labeling assay.RESULTS:Intravenous infusion of MSCs was more effective than intraperitoneal treatment(P<0.001)in reducing the clinical and histopathologic severity of colitis,which includes weight loss,diarrhea and inflammation.An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells.This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)];and by the up-regulation of anti-inflammatory cytokines(IL-10 and IL-4).Intravenous transplantation alsoinduced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs,which did not occur with intraperitoneal transplantation(P=0.006).An increase in apoptotic T cells was observed after intravenous,but not intraperitoneal,MSC infusion,suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation(P=0.027).CONCLUSION:Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.
文摘AIM:To investigate the therapeutic efficacy of short- term, multiple daily dosing of intravenous interferon (IFN) in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS:IFN-β was intravenously administered at a total dose of 102 million international units (MIU) over a period of 28 d in 26 patients positive for HBeAg and HBV-DNA. IFN-beta was administered at doses of 2 MIU and 1 MIU on d 1, 3 MIU twice daily from d 2 to d 7, and 1 MIU thrice daily from d 8 to d 28. Patients were followed up for 24 wk after the end of treatment. RESULTS:Six months after the end of the treatment, loss of HBV-DNA occurred in 13 (50.0%) of the 26 patients, loss of HBeAg in 9 (34.6%), development of anti-HBe in 10 (38.5%), HBeAg seroconversion in 8 (30.8%), and normalization of alanine aminotransferase (ALT) levels in 11 (42.0%). CONCLUSION:This 4-wk long IFN-β therapy, which was much shorter than conventional therapy lasting 12 wk or even more than 1 year, produced therapeutic effects similar to those achieved by IFN-α or pegylated- IFN-α (peg-IFN). Fewer adverse effects, greater efficacy, and a shorter treatment period led to an improvement in patients’ quality of life. IFN-β is administered intravenously, whereas IFN-α is administered intramuscularly or subcutaneously. Because both interferons are known to bind to an identical receptor and exert antiviral effects through intracellular signal transduction, the excellent results of IFN-β found in this study may be attributed to the multiple doses allowed by the intravenous route.
文摘BACKGROUND Detergent poisoning mostly occurs through oral ingestion(>85%),ocular exposure(<15%),or dermal exposure(<8%).Reports of detergent poisoning through an intravenous injection are extremely rare.In addition,there are very few cases of renal toxicity directly caused by detergents.Here,we report a unique case of acute kidney injury caused by detergent poisoning through an accidental intravenous injection.CASE SUMMARY A 61-year-old man was intravenously injected with 20 mL of detergent by another patient in the same room of a local hospital.The surfactant and calcium carbonate accounted for the largest proportion of the detergent.The patient complained of vascular pain,chest discomfort,and nausea,and was transferred to our institution.After hospitalization,the patient’s serum creatinine level increased to 5.42 mg/dL,and his daily urine output decreased to approximately 300 mL.Renal biopsy findings noted that the glomeruli were relatively intact;however,diffuse acute tubular injury was observed.Generalized edema was also noted,and the patient underwent a total of four hemodiafiltration sessions.Afterward,the patient’s urine output gradually increased whereas the serum creatinine level decreased.The patient was discharged in a stable status without any sequelae.CONCLUSION Detergents appear to directly cause renal tubular injury by systemic absorption.In treating a patient with detergent poisoning,physicians should be aware that the renal function may also deteriorate.In addition,timely renal replacement therapy may help improve the patient’s prognosis.
文摘High-performance liquid chromatographic (HPLC) analysis of fluorouracil (5-FU) content of the blood and colon of rabbits is described. There was no marked difference in the plasma 5-FU level and blood concentration time curve following intravenous (I. V.) (ear vein) or intraarterial (I.A.) (inferior mesenteric artery) injection of 5-FU 15 mg/kg. However, the distribution of 5-FU in the colon after IA. administration was quite different that after I.V. administration. At 10, 20 and 30 minutes, the 5-FU content in the colon was shown to be 31-, 17- and 14-fold higher with I.A. than with I.V.. Colonic tissue AUCo-480 min. was 2453 and 690 min/mg/ml respectively (p<0.05). It is suggested that to inject 5-FU into selected arteries to treat advanced colorectal cancer may be more useful than I.V. administration.
基金supported by the National Natural Science Foundation of China(82072060 and 81571807,China)the Fundamental Research Funds for the Central Universities(XDJK2019TY002 and 2020CDJQY-A041,China)+1 种基金the Natural Science Foundation Project of Chongqing(cstc2020jcyjmsxm X0292,China)the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2018029,China)。
文摘Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v.and oral routes.
基金supported by the Knowledge Innovative Program of the Chinese Academy of Sciences (No.KZCX2-EW-404)the National Natural Science Foundation of China (No:21207152,20921063,21177151)
文摘Graphene oxide(GO)displays promising properties for biomedical applications including drug delivery and cancer therapeutics.However,GO exposure also raises safety concerns such as potential side effects on health.Here,the biological effects of GO suspended in phosphate buffered saline(PBS)with or without 1% nonionic surfactant Tween 80 were investigated.Based on the ex vivo experiments,Tween 80 significantly affected the interaction between GO and peripheral blood from mice.GO suspension in PBS tended to provoke the aggregation of diluted blood cells,which could be prevented by the addition of Tween 80.After intravenous administration,GO suspension with or without 1% Tween 80 was quickly eliminated by the mononuclear phagocyte system.Nevertheless,GO suspension without Tween 80 showed greater accumulation in lungs than that containing 1% Tween 80.In contrast,less GO was found in livers for GO suspension compared to Tween 80 assisted GO suspension.Organs including hearts,livers,lungs,spleens,kidneys,brains,and testes did not reveal histological alterations.The indexes of peripheral blood showed no change upon GO exposure.Our results together demonstrated that Tween 80 could greatly alter GO's biological performance and determine the pattern of its biodistribution in mice.
基金funded by the National Natural Science Foundation Council of China(No.81172906)the National Key Technology R&D Program of China(No.2012BAK02B02-2)International technology cooperation plan project in Shanxi Province(No.2012081053).
文摘The objective of the study was to compare the concentration of lidocaine in different body fluids/tissues after subarachnoid space and intravenous administrations of a lethal dose of lidocaine.Totally 18 dogs were used in the experiment.Six dogs were given subarachnoid anesthesia,another were given an intravenous injection of a dose of 75 mg/kg weight of lidocaine hydrochloride in 5 min and the last 6 dogs were used as the blank control dogs and given a subarachnoid space injection or a femoral artery injection of the same volume of sodium chloride.As soon as its vital signs disappeared,each dog was dissected and the specimen,such as brain,cerebrospinal fluid(CSF)in lateral ventricle,CSF in subarachnoid space,spinal cord(cervical spinal cord,thoracic spinal cord,lumbar spinal cord,and waist spinal cord),heart,lung,liver,spleen,kidney,bile,urine,heart blood,peripheral blood,muscle in injection location,and muscle in no injection location,were collected for analysis of lidocaine immediately.Analysis was performed with gas chromatography‑mass spectrometry(GC‑MS).From the maximum to the minimum,the order of lidocaine concentration detected in the subarachnoid space‑administered dogs was as follows:CSF in subarachnoid space,waist spinal cord,thoracic spinal cord,CSF in lateral ventricle,lumbar spinal cord,cervical spinal cord,lung,kidney,muscle in injection location,heart,brain,spleen,heart blood,liver,peripheral blood,bile,muscle in no injection location,and urine.The order of lidocaine concentration detected in the intravenously administered dogs was as followed:Kidney,heart,lung,spleen,brain,liver,peripheral blood,bile,heart blood,cervical spinal cord,thoracic spinal cord,muscle in injection location,lumbar spinal cord,muscle in no injection location,CSF in subarachnoid space,urine,and CSF in lateral ventricle.The maximum concentration of lidocaine was detected in the subarachnoid space CSF of subarachnoid space‑administered dead dogs,while in intravenously injected dead dogs,the maximum concentration of lidocaine was detected in the kidney.Our study provides some useful data for the forensic identification of epidural anesthesia accidents to decide the way the lidocaine enters the body.