Preemptive therapy for hepatitis B patients undergoing chemotherapy

Abstract   In areas where hepatitis B virus (HBV) is endemic, the increased use of cytotoxic or immunosuppressive therapy has resulted in an increased incidence of liver-related morbidity and mortality due to HBV reactivation in patients infected with the virus. As the hepatitis is preceded by HBV virological reactivation, administration of effective antiviral therapy to HBV (anti-HBV) such as lamivudine preemptively before or at the initiation of cytotoxic therapy and to cover the entire period of immunsuppression, has greatly reduced the risk of liver-related morbidity and mortality due to HBV reactivation. However, such an early 'preemptive' approach runs the risk of over-treating patients who might not be suffering from HBV reactivation with nucleoside analog. In addition, the duration of therapy with nucleoside analog, such as lamivudine, would be longer with this approach. Taken together, such an indiscriminant preemptive approach could result in an increased risk of developing HBV viral resistance. Indeed, severe liver damage due to the development of mutations in the polymerase gene related to lamivudine, namely at M204V and at L180M, has been reported in hepatitis B surface antigen (HBsAg) positive recipients of allogeneic bone marrow transplantation and who were treated with preemptive lamivudine. In order to further optimize the management of postchemotherapy HBV reactivation, more studies aiming to identify risk factors for HBV reactivation after chemotherapy should be undertaken.     

Use of a 24-kilodalton Trypanosoma cruzi recombinant protein to monitor cure of human Chagas' disease.

A 24-kDa recombinant protein from Trypanosoma cruzi (rTc24) was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blot (immunoblot) tests to identify treated chagasic patients considered parasitologically cured on the basis of persistently negative tests of hemocultures and lytic antibodies. Some of these patients were termed dissociated because their sera, although negative by the complement-mediated lysis test, were positive by conventional serology. The negative lysis test indicates the absence of active infection after specific treatment, but this assay requires live and infectious parasites and cannot be used easily in a laboratory routine. Here we tested rTc24 by ELISA and Western blotting as an alternative for the complement-mediated lysis test. For the group of patients with active infection despite the treatment (uncured patients), all the sera tested recognized rTc24 in both tests. For the dissociated patients, approximately 80% of the sera did not react with rTc24 in the ELISA or in Western blots, in agreement with the negative complement-mediated lysis tests. Thus, the 24-kDa T. cruzi recombinant antigen, when used for initial trials to evaluate cure of chagasic patients submitted to specific treatment, will allow the identification of most, but not all, cases.     

MRI T2*技术对中、重型β地中海贫血患者心脏及肝脏铁沉积状态的评估

目的：了解中、重型β地中海贫血患者体内铁沉积状况。方法：对39例中、重型β地中海贫血患者的输血、排铁的情况进行统计,检测患者体内铁蛋白水平,并运用MRI T2*技术检测心脏及肝脏铁沉积状况。结果：患者血清铁蛋白水平最低为1500 ng/mL,最高达 11491 ng/mL。肝脏铁重度沉积者15例（38%）,中度沉积者15例（38%）,轻度沉积者7例（18%）,正常者 2例（5%）。 心脏铁重度沉积者7例（18%）,轻度沉积者5例（13%）,正常者27例（69%）。1例出现心律紊乱症状,4例年龄超过20岁者均呈现性腺功能发育不全。大多患者因家庭经济原因未能进行规律输血及排铁治疗,且开始排铁时间较晚。患者血清铁蛋白水平与开始排铁的时间、剂量密切相关。结论：未进行早期规律的输血和排铁治疗的地中海贫血患者,体内铁的沉积发生年龄早,易早期出现重要器官的功能损害而引发相关并发症,应引起临床医师和患者家属的高度重视并制定相应的诊疗措施提高患者的生活质量。     

Pattern of glomerulonephritis in Chinese population: The effect of renal biopsy on the therapeutic decision

A retrospective analysis of 190 consecutive renal biopsies was undertaken to assess the pattern of glomerulonephritis in Chinese, and the role of renal biopsy in paediatric nephrology. Minimal change nephropathy, IgA nephropathy and membranous nephropathy comprised 41%, 16% and 13% of primary glomerular diseases, respectively. Minimal change nephropathy accounted for only 61% of patients with idiopathic nephrotic syndrome. In 76 patients the provisional clinicopathological diagnosis was shown to be incorrect or uncertain, and correct diagnosis was made solely on histologtcal examination. In 47 cases a substantial change in therapy occurred on the basis of biopsy results. These data suggest that the practice of renal biopsy in paediatric nephrology performed appropriately in carefully selected patients is a useful procedure.     

Potential antimalarials from Nigerian plants: a review

Malaria, caused by parasites of the genus Plasmodium, is one of the leading infectious diseases in many tropical regions, including Nigeria, a West African country where transmission occurs all year round. Many of the inhabitants use plants as remedies against fever and other symptoms of acute malaria, as reported herein. Some of these plants have their antimalarial efficacies scientifically demonstrated and the active compounds isolated with their probable mechanisms of action studied. Medicinal plants are used to treat diseases also where the biodiversity of plants occur in parallel with endemic transmission of malaria. This review focuses on medicinal plants which are used to treat malaria in Nigeria, and on antimalarial testing of extracts and purified compounds from plants. Some show intense activity against malaria parasites in vitro and in experimentally infected mice. The search for new drugs based on plants is important due to the emergence and widespread of chloroquine-resistant and multiple drug-resistant malaria parasites, which require the development of new antimalarials. An acquaintance with antimalarial plants may be a springboard for new phytotherapies that could be affordable to treat malaria, especially among the less privileged native people living in endemic areas of the tropics, mostly at risk of this devastating disease.     

Synthesis and antimalarial activity of semicarbazone and thiosemicarbazone derivatives

Seventeen semicarbazone and thiosemicarbazone derivatives were prepared and tested in vitro against a chloroquine resistant strain of Plasmodium falciparum (W2) to evaluate their antiplasmodial potential. Three thiosemicarbazones were found to be active against the parasite and non-toxic to human peripheral blood mononuclear cells (PBMC). Among these, compound 5b presented the lowest IC50 value against P. falciparum (7.2 microM) and was the least toxic in the PBMC proliferation assay (IC50=73.5 microM). It was selected for in vivo tests on mice infected with Plasmodium berghei (strain NK-65). The thiosemicarbazone 5b was able to reduce the parasitaemia by 61% at 20 mg/kg on day 7 after infection without any sign of toxicity to the animals. In comparison, the standard drug chloroquine at 15 mg/kg showed a reduction around 95%. These in vitro and in vivo results make 5b an interesting lead for further development.