Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. For...Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.展开更多
The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and...The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.展开更多
This paper focuses on women as victims of violence as shown in films. Seven German films were selected for the analysis, namely Die Fremde （2010） by Feo Aladag, Die Frau des Polizisten （2013） by Philip Groning, Fe...This paper focuses on women as victims of violence as shown in films. Seven German films were selected for the analysis, namely Die Fremde （2010） by Feo Aladag, Die Frau des Polizisten （2013） by Philip Groning, Festung （2011） by Kirsi Liimatainen, Reeperbahn （2016） by Timo Rose, Schneeland （2005） by Hans W. GeiBendorfer, Der Brand （2010） by Brigitte Berteleund and L＇amour （2000） by Philip Groning. There were three main research questions： （1） What kinds of violence against women are represented in selected German films; （2） Why do the women in these films become victims of violence; and （3） How do the women in these films find solutions to the problem？ There are four forms of violence in the analyzed films： physical violence, psychological violence, sexual violence, and witnessed violence. Physical violence is found in all the films, however, witnessed violence appears only in two films with young female characters. The other two kinds of violence are also found in most of the films. The reasons why women become victims of violence are weakness, love, poverty and carelessness. All of these factors appear in different types of women. Furthermore, the female characters in the films react differently to violence. Some women flee from their abusers because they fear or cannot fight with them. In other cases, they accept the violence with patience, or they take revenge on their offenders to get justice or stop the violence.展开更多
文摘Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.
基金supported in part by NIH grant AI054715 to C.C.B.
文摘The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.
文摘This paper focuses on women as victims of violence as shown in films. Seven German films were selected for the analysis, namely Die Fremde （2010） by Feo Aladag, Die Frau des Polizisten （2013） by Philip Groning, Festung （2011） by Kirsi Liimatainen, Reeperbahn （2016） by Timo Rose, Schneeland （2005） by Hans W. GeiBendorfer, Der Brand （2010） by Brigitte Berteleund and L＇amour （2000） by Philip Groning. There were three main research questions： （1） What kinds of violence against women are represented in selected German films; （2） Why do the women in these films become victims of violence; and （3） How do the women in these films find solutions to the problem？ There are four forms of violence in the analyzed films： physical violence, psychological violence, sexual violence, and witnessed violence. Physical violence is found in all the films, however, witnessed violence appears only in two films with young female characters. The other two kinds of violence are also found in most of the films. The reasons why women become victims of violence are weakness, love, poverty and carelessness. All of these factors appear in different types of women. Furthermore, the female characters in the films react differently to violence. Some women flee from their abusers because they fear or cannot fight with them. In other cases, they accept the violence with patience, or they take revenge on their offenders to get justice or stop the violence.
