ABSTRACT
Non-small cell lung cancer is recognized as the deadliest cancer across the globe. In some areas, it is more common in women than even breast and cervical cancer. Its rise, vaulted by smoking habits and increasing air pollution, has garnered much attention and resource in the medical field. The first lung cancer treatments were developed more than half a century ago. Unfortunately, many of the earlier chemotherapies often did more harm than good, especially when they were used to treat genetically unsuitable patients. With the introduction of personalized medicine, physicians are increasingly aware of when, how, and in whom, to use certain anti-cancer agents. Drugs such as tyrosine kinase inhibitors, anaplastic lymphoma kinase inhibitors, and monoclonal antibodies possess limited utility because they target specific oncogenic mutations, but other drugs that target mechanisms universal to all cancers do not. In this review, we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors (
ABSTRACT
Clostridium perfringens is considered one of the main causative agents of superacute enterocolitis, usually fatal in the equine species, due to the action of the ß toxin, and is responsible for causing severe myonecrosis, by the action of the α toxin. The great importance of this agent in the equine economy is due to high mortality and lack of vaccines, which are the main form of prevention, which guarantee the immunization of this animal species. The aim of this study was to evaluate three different concentrations (100, 200 and 400µg) of C. perfringens α and ß recombinant toxoids in equine immunization and to compare with a group vaccinated with a commercial toxoid. The commercial vaccine was not able to stimulate an immune response and the recombinant vaccine was able to induce satisfactory humoral immune response in vaccinated horses, proving to be an alternative prophylactic for C. perfringens infection.(AU)
Clostridium perfringens é considerado um dos principais agentes causadores de enterocolites superagudas, geralmente fatais na espécie equina, devido à ação da toxina ß, além de ser responsável por causar quadros graves de mionecrose, pela ação da toxina α. A grande importância desses agentes na equinocultura, deve-se a elevada mortalidade e a inexistência de vacinas, principal forma de prevenção, que garantam a imunização dessa espécie animal. O objetivo deste trabalho foi avaliar três diferentes concentrações (100, 200 e 400µg) dos toxóides recombinantes α e ß de C. perfringens na imunização de equinos, bem como comparar com um grupo vacinado com um toxóide comercial. A vacina comercial não se mostrou capaz de estimular uma resposta imune e a vacina recombinante foi capaz de induzir resposta imune humoral satisfatória em equinos vacinados, provando ser uma alternativa profilática para infecção por C. Perfringens.(AU)
Subject(s)
Animals , Toxoids , Enterocolitis, Pseudomembranous/veterinary , Vaccines, Synthetic/therapeutic use , Clostridium perfringens/immunology , Gas Gangrene/veterinary , Horses , Immunization/veterinaryABSTRACT
Objective To evaluate the role of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in remote ischemic preconditioning-induced reduction of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods Sixty-eight healthy male C57BL/6 mice,aged 6-8 weeks,weighing 22-26 g,were divided into 4 groups (n =17 each) using a random number table:control group (group C),ALI group,remote ischemic preconditioning group (group RIPC) and brusatol plus remote ischemic preconditioning group (group B+RIPC).Normal saline 100 μl was intratracheally instilled in group C.ALI was induced by intratracheal instillation of LPS 5 mg/kg in group ALI.Mice in group RIPC were subjected to 6 cycles of 5-min ischemia followed by 5-min reperfusion in the right hindlimbs using a tourniquet,and 1 h later the model of ALI was established.Nrf2 inhibitor brusatol 2 mg/kg (in 100 μl of 1％ dimethyl sulfoxide) was intraperitoneally injected every other day for 10 days prior to establishment of the ALI model in group B.Brusatol 2 mg/kg was intraperitoneally injected every other day for 10 days prior to establishment of the ALI model,and remote ischemic preconditioning was performed at 1 h before establishment of the ALI model in group B+RIPC.Seven mice in each group were selected at 24 h after establishment of the ALI model,and bronchoalveolar lavage fluid (BALF) was collected for determination of protein concentrations and neutrophil count.Mice were then sacrificed and lungs were removed for determination of lung water content,myeloperoxidase (MPO) activity,contents of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α),and expression of Nrf2,HO-1 and high-mobility group box 1 protein (HMGB1) in lung tissues (by Western blot) and for examination of pathological changes (with a light microscope).Results Compared with group C,the lung water content,MPO activity,contents of IL-1β and TNF-α,and neutrophil count and protein concentrations in BALF were significantly increased,and the expression of Nrf2,HO-1 and HMGB1 was up-regulated in group ALI (P＜ 0.05).Compared with group ALI,the lung water content,MPO activity,contents of IL-1β and TNF-α,and neutrophil count and protein concentrations in BALF were significantly decreased,the expression of Nrf2 and HO-1 was up-regulated,and the expression of HMGB1 was down-regulated (P＜0.05),and the pathological changes were significantly attenuated in group RIPC.Compared with group RIPC,the lung water content,MPO activity,contents of IL-1β and TNF-α,and neutrophil count and protein concentrations in BALF were significantly increased,the expression of Nrf2 and HO-1 was down-regulated,and the expression of HMGB1 was up-regulated (P＜0.05),and the pathological changes were aggravated in group B+RIPC.Conclusion The activation of Nrf2/HO-1 signaling pathway is involved in remote ischemic preconditioning-induced reduction of LPS-induced ALI in mice.
ABSTRACT
Objective To study the effect of early enteral nutrition ( EN ) on the serum endotoxin and intestinal permeability in patients with severe acute pancreatitis ( SAP ) .Methods Seventy patients with SAP were selected as study objects ,and they were divided into parenteral nutrition ( PN) group and EN group according to the random number table method ,with 35 cases in each group.The PN group was given PN intervention ,while the EN group was given EN intervention .The levels of serum endotoxin and the ratio of the excretion rates of urinary lactulose and mannitol excretion before and after 1 week and 2 weeks of intervention , and the levels of inflammatory factors before and after treatment were measured .Results Before intervention ,the levels of serum endotoxin and the ratio of the excretion rates of urinary lactulose and mannitol excretion had no statistically significant differences between the two groups (t=0.274,P=0.452;t=0.035,P=0.885).After 1 week and 2 weeks of intervention,the levels of serum endotoxin and the ratio of the excretion rates of urinary lactulose and mannitol excretion in the EN group were significantly lower than those in the PN group (t=9.024,10.761,P=0.000,0.000;t=6.935,8.358,P=0.000, 0.000).After treatment,the levels of TNF -α,IL-1β,IL-6 and IL-8 in the EN group were significantly lower than those in the PN group (t=12.674,10.318,9.754,8.307,P=0.000,0.000,0.000,0.002).Conclusion EN has significant influence on the serum endotoxin and intestinal permeability in patients with SAP ,and compared with PN,EN can promote the clearance of serum endotoxin ,reduce the permeability of intestinal mucosa ,and it is worth promoting.
ABSTRACT
The risk factors of Clostridium difficile infections increased in recent years , such as the underlying disease, hospitalization duration, age, the use of antibiotics, the use of proton pump inhibitors and so on.The rate of Clostridium difficile infection and recurrence are still high despite the appear of new antibiotics such as rifaximin, nitazoxanide, tigecycline, ramoplanin, fidaxomicin, and non-antimicrobial such as drugs toxin neutralizer chamber , biological therapeutic agents , fecal transplantation , systemic antibody method , intravenous immunoglobulin and so on.The vaccine is the most ideal way of prevention and treatment of Clostridium difficile infection.The research in Clostridium difficile vaccine lasted for nearly 20 years.Except the monoclonal antibody vaccine and toxoid vaccine against toxin A and toxin B have achieved better results in the human , some recombinant vaccines against the toxin receptor and the key pathogenic factor of Clostridium difficile also achieved good effect in animal.
ABSTRACT
Myocarditis is an inflammatory disease of the myocardium caused by various infectious or noninfectious triggers. Although viral infections are important causes of myocarditis, some drugs or toxins can also cause myocarditis. We report a case of life-threatening fulminant myocarditis which followed an extensive coffee diet program. Despite medical treatment, the patient was not able to maintain hemodynamic stability. She was supported by extracorporeal membrane oxygenation and completely recovered 3 months later.
Subject(s)
Humans , Coffee , Diet , Extracorporeal Membrane Oxygenation , Hemodynamics , Myocarditis , Myocardium , ToxoidsABSTRACT
The effect of injection of one cc. Clostridium tetani toxoid, one week after a clinical cure of malaria, and repeated after three weeks, was tried on patients who had contracted malaria elsewhere in the Philippines, but who had settled in Manila ( non-endemic area.) Observation was carried on until the first appearance of relapse for a period of one year for each case. The percentage of relapse in the experimental groups did not vary from those of the corresponding control groups. The results show that Clostridium tetani toxoid does not exert any anti-relapse activity in malaria, contrary to the claim of Dr. E.Y. Garcia.(Summary)