Clinical trials for Chagas disease: etiological and pathophysiological treatment.

Chagas disease (CD) is caused by the flagellate protozoan Trypanosoma cruzi. It is endemic in Latin America. Nowadays around 6 million people are affected worldwide, and 75 million are still at risk. CD has two evolutive phases, acute and chronic. The acute phase is mostly asymptomatic, or presenting unspecific symptoms which makes it hard to diagnose. At the chronic phase, patients can stay in the indeterminate form or develop cardiac and/or digestive manifestations. The two trypanocide drugs available for the treatment of CD are benznidazole (BZ) and nifurtimox (NFX), introduced in the clinic more than five decades ago. WHO recommends treatment for patients at the acute phase, at risk of congenital infection, for immunosuppressed patients and children with chronic infection. A high cure rate is seen at the CD acute phase but better treatment schemes still need to be investigated for the chronic phase. There are some limitations within the use of the trypanocide drugs, with side effects occurring in about 40% of the patients, that can lead patients to interrupt treatment. In addition, patients with advanced heart problems should not be treated with BZ. This is a neglected disease, discovered 114 years ago that still has no drug effective for their chronic phase. Multiple social economic and cultural barriers influence CD research. The high cost of the development of new drugs, in addition to the low economical return, results in the lack of investment. More economic support is required from governments and pharmaceutical companies on the development of more research for CD treatment. Two approaches stand out: repositioning and combination of drugs, witch drastically decrease the cost of this process, when compared to the development of a new drug. Here we discuss the progress of the clinical trials for the etiological and pathophysiological treatment for CD. In summary, more studies are needed to propose a new drug for CD. Therefore, BZ is still the best option for CD. The trials in course should clarify more about new treatment regimens, but it is already possible to indicate that dosage and time of treatment need to be adjusted.

Current progress in the treatment of nonarteritic anterior ischemic optic neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Nonarterial anterior ischemic optic neuropathy(NAION)is a group of common optic nerve diseases that seriously endanger visual function. It is resulted from insufficient perfusion of the posterior ciliary artery, which causes acute ischemia, structural and functional disorders of the optic nerve, and ultimately leads to hypopsia and even vision loss. The etiology and pathogenesis of this disease is complex. It is nowadays considered that multiple factors including local anatomy, risk of systemic vascular cause this disease together, which result in no clear, unified and recognized treatment. Early detection, diagnosis and treatment are of great significance in the prognosis of NAION. Possible therapeutic methods include etiological treatment, drug therapy, traditional Chinese medicine(TCM)treatment, combined medication, optic nerve sheath decompression, adjuvant treatments and exosomes. With the continuous development and application of various anti-NAION drugs in recent years, a variety of therapeutic methods have been proposed, especially with the exosomes as the research focus. In order to better treat NAION with improvement of the cure rate and guidance for clinical work, this paper mainly reviews the progress in the treatment of NAION in recent years.

Neural network analysis of the correlation between malnutrition-induced stomatitis and vitamin B12 and folic acid / 口腔疾病防治

Objective@# A model was built by neural network analysis to study the relationship between different degrees of vitamin B12 and folic acid deficiency and malnutrition-induced stomatitis.@*Methods@# Data from 30 healthy volunteers and 30 patients with malnutrition-induced stomatitis were collected. The distribution of lesions, the number of affected sites and clinical manifestations were recorded, and the severity was scored. The levels of vitamin B12 and folic acid in the peripheral blood of the two groups were simultaneously measured. The SPSS software was used to analyze the correlation between vitamin B12 and folic acid levels in the peripheral blood of patients with malnutrition-induced stomatitis and healthy volunteers, and the MATLAB software package was used to analyze the data via a neural network.@*Results@#The levels of vitamin B12 and folic acid significantly correlated with the grade of malnutrition-induced stomatitis. Simultaneous B12 and folic acid deficiency linearly correlated with the occurrence and severity of malnutrition-induced stomatitis. Based on this correlation, a thermogram model of malnutrition-induced stomatitis was constructed.@*Conclusion@# Malnutrition-induced stomatitis is closely related to vitamin B12 and folic acid deficiency. Their synergistic effect may promote the occurrence and development of malnutrition-induced stomatitis. The construction of the malnutrition-induced stomatitis model aids the targeted etiological treatment of patients with moderate and severe deficiency to prevent malnutrition-induced stomatitis.

Mice Intragastric Infected with Insect and Blood Trypomastigotes of Trypanosoma cruzi IV: Differences and Similarities on the Evolution Profile and Response to Etiological Treatment.

PURPOSE: Our goal was to analyze the outcome of infection and response to benznidazole (BZ) treatment in mice intragastrically inoculated with trypomastigotes forms of Trypanosoma cruzi from different origins. METHODS: Twenty-four Swiss mice were divided in two groups and inoculated, by gavage, with 1 × 104 blood trypomastigotes (BT) or insect-derived metacyclic trypomastigotes (IT) of AM14 strain (T. cruzi IV). Half of the animals of each group were treated with BZ (TBZ), from 10 to 30th days after the inoculation, and the other constituted the untreated control groups (NT). After the etiological treatment, all mice were immunosuppressed with cyclophosphamide for three weeks. Parasitological and molecular parameters, infectivity, cumulative mortality, and reactivation post-immunosuppression rates were obtained. RESULTS: Animals inoculated with BT showed lower pre-patent period and early day of the maximum parasitemia, as well as a higher maximum peak of parasitemia than the IT animals. However, both, BT and IT animals, did not respond to BZ treatment (0.0% of cure). CONCLUSION: We conclude that the infective form influences in the outcome of infection, but not the response to the etiological treatment in mice intragastrically infected with the T. cruzi IV strain studied.

Benznidazole: Hero or villain of cellular immune response in chronic Chagas disease patients?

Although the treatment of chronic Chagas disease (CCD) patients with Benznidazole (Bz) is still controversial, its use may prevent or delay the progression of the disease to the most severe forms. One of the main factors that can influence the effectiveness of the treatment is the possible cooperation between drug effect and the host immune response. Herein, we evaluated the immune response of peripheral blood mononuclear cells (PBMCs) infected with Trypanosoma cruzi and submitted to Bz treatment. Blood samples of CCD patients (n = 7) and non-infected individuals (n = 6) were drawn to obtain PBMCs. After cell culture, the supernatants were harvested and stored, and the cell analyzed by flow cytometer. The results showed that Bz positively regulated the molecular process of cell activation (CD80) and antigen presentation (HLA-DR), increased phagocytosis receptor and macrophage activation (CD64), and did not induce an exacerbated immune response. In conclusion, these results highlight the relevance of using Bz that, despite not being a true hero, it is also not a villain, as it presents a wide range of pharmacological/immunological response interactions, important for the immune balance in the clinical progression of CCD.

Progress in etiological treatment of non-viral severe liver diseases / 中华临床感染病杂志

Severe liver diseases have various etiology.Hepatitis B and hepatitis C are commonly seen in China.However,alcoholic liver disease, autoimmune liver disease (ALD) and other non-viral severe liver diseases have shown an upward trend in recent years.There are no special therapeutical methods for severe alcoholic liver disease so far, glucocorticoids and pentoxifylline are mainly used for etiological treatment.The autoimmune liver disease is still one of the remarkable problems in the filed of liver diseases;at present, immunosuppressive agents and corticosteroids are routinely used for this liver disease, study on transduction pathway of biological agents interfering signals is expected to be a new therapy for ALD.The Wilson's disease is treated by administrating in a staggered manner or alternate manner to avoid the overlap of adverse reactions, while cell transplantation therapy and gene therapy will be the direction of future research.In conclusion, effective therapy should be given with reference to detailed condition, so as to improve survival rate in patients with severe liver diseases.

Studies Progress Of Comprehensive Treatment Of Diabetic Peripheral Neuropathy / 中国药师

Diabetic peripheral neuropathy( DPN) is one of the most common chronic complications and the disabling one, which is related to chronic hyperglycemia and microvascular changes. Currently, the treatments of diabetic peripheral neuropathy contains glu-cose control,pain management,etiological treatment,prevention and remove risk factors. So we make a review on the progress on the treatment of DPN by now , providing a scientific basis to a advanced and effective program.

132 cases of gerontol delirium:a clinical study / 医学研究生学报

Objective To investigate clinical features , outcomes and prognosis gerontol delirium . Methods Patients with gerontol delirium diagnosed between January 2011 and January 2013 were identified by a retrospective review of records in the Nanjing General Hospital of Nanjing Military Command .Totally 132 patients were included , 59 females and 73 males, with a median age of 71.4 years (range 65-97).The diagnostic criteria were based on the DSM-Ⅳ and Delirium Rating Scale.Dementia, depression, mental retardation and other cognitive dysfunction were excluded .General condition of patients , etiology , clinical features , treatment and prognosis were all performed using the SPSS 20.0 for windows.A P value of <0.05 was considered as significant . Results Disturbance of consciousness were observed in all 132 patients.Old age, coma and serious infection in the course , endotracheal intuba-tion and(or) tracheotomy, a variety of basic diseases all come up with poor prognosis . Conclusion Delirium progresses quickly. Etiological treatment can help to control the conditions of delirium .

Twenty-one patients with thrombotic thrombocytopenic purpura:a clinical study / 中华急诊医学杂志

Objective To investigate clinical features, outcomes and laboratory findings of thrombotic thrombocytopenic purpura (TTP).Methods Patients with TTP admitted between April 2006 and January 2013 were identified by a retrospective review of records.Totally 21 patients were available,15 females and 6 males,with a median age of 46 years (ranged 18-66).The diagnostic criteria were defined by:(1)thrombocytopenia (<100 ×9 L-1)without other identifiable causes;(2)a negative Coombs'test and hemolytic anemia with schistocytes on the peripheral blood smear;and only those patients meeting the criteria for TTP,both on clinical presentation and their clinical course,were included in this study. Exclusion criteria were:(1)patients discharged or dead within 24 hours after admission;(2)patients treated with plasma exchange therapy in other hospitals;(3)medical data were incomplete;(4)cannot be followed up;and (5 )other causes of thrombotic microangiopathies.General condition of patients,etiology, clinical features,treatment and prognosis were analyzed by using the SPSS 20.0 software.P value of <0.05 was considered as significant.Results Hemolytic anemia and thrombocytopenia appeared in all of the patients. Twelve patients (57.2%) had the classical pentad manifestations of TTP (fever, thrombocytopenia,microangiopathic hemolytic anemia,symptoms of nervous system,renal injury),seven patients (33.3%)had tetrad of TTP clinical manifestations (thrombocytopenia,microangiopathic hemolytic anemia,symptoms of nervous system,fever or renal injury),and only two patients showed the triad manifestations of TTP (thrombocytopenia, microangiopathic hemolytic anemia, symptoms of nervous system).In our studies,seven patients accepted plasmapheresis,and five of them (71.4%)achieved remission.Conclusions TTP progresses quickly.Plasmapheresis is still the treatment of choice for TTP patients.Etiological treatment can help to control the conditions of patients with TTP.

A serological, parasitological and clinical evaluation of untreated Chagas disease patients and those treated with benznidazole before and thirteen years after intervention

The etiological treatment of Chagas disease is recommended for all patients with acute or recent chronic infection, but controversies remain regarding the benefit of chemotherapy and interpretations of the parasitological cure after etiological treatment. This study compares the laboratory and clinical evaluations of Chagas disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease patients (29 treated with benznidazole and 29 untreated) were matched at the time of treatment based on several variables. Conventional serology revealed the absence of seroconversion in all patients. However, lower serological titres were verified in the treated group, primarily among patients who had the indeterminate form of the disease. Haemoculture performed 13 years after the intervention was positive for 6.9% and 27.6% of the treated and untreated patients, respectively. Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated and untreated patients, respectively. Patients who presented with the indeterminate form of the disease at the beginning of the study exhibited less clinical progression (17.4%) compared with the untreated group (56.5%). Therefore, this global analysis revealed that etiological treatment with benznidazole may benefit patients with respect to the clinical progression of Chagas disease and the prognosis, particularly when administered to patients with the indeterminate form of the disease.

Prognosis and Etiological Treatment of Cardiogenic Syncope in Children / 实用儿科临床杂志

Objective To explore the prognosis and etiological treatment of cardiogenic syncope in children.Methods The cause,clinical manifestation,treatment and prognosis of 45 children with syncope were made in affiliated hospital of Qingdao medical university were su mmarized and analyzed.They were divided into arhythmia group and other groups,the former included myocarditis,dilated cardiomyopathy,and post-operation of congenital heart disease and the latter included tetralogy of fallot,pulmonary stenosis,hypertrophic cardiomyopathy,pericarclial effusion,and right atrial myxoma.Results There were 29 cases(64.44%) with arrhythmia in this group,of which there were 18 cases with complete atrioventricular block(CAVB),2 cases with second degree type Ⅱ atrioventricular block,3 cases with ventricular tachycardia,2 cases with bradycardia,2 cases with atrial flutter,1 case with supraventricular tachycardia,and 1 case with nonconducting atrial premature.There were 16 cases(35.56%) with other etiologies,of which there 8 cases with tetralogy of Fallot,2 cases with pulmonary stenosis,hypertrop-hic cardiomyopathy,pericardial effusion,and right atrial myxoma,respectively.Children with CAVB,bradycardia,or ventricular tachycardia resulted from viral myocarditis were given anti-virus medicine,protecting myocardium,neoepinephrine,and intravenous vitamin C 100-200 mg/(kg?d).Dexamethasone 1-2 mg/(kg?d) was given in earlier period for short course,and some children were given human ?-globulin.Eight cases were placed temporary pacemaker because of unsatisfactory therapeutic efficacy,and 1 case was placed permanent pacemaker.In all,38 cases(84.44%)were cured,1 case(2.22%)was improved,and 4 cases(8.88%) died.Conclusions Cardiogenic syncope is pediatric emergency and shall be treated immediately.Temporary pacemaker shall be placed at the right moment.