Cassia alata and the preclinical search for therapeutic agents for the treatment of opportunistic infections in AIDS patients.

In our search for therapeutic agents from natural sources with potential for the treatment of opportunistic infections in patients afflicted with acquired immunodeficiency syndrome (AIDS), we investigated antibacterial and antifungal activities of water extracts of Cassia alata (C. alata). The extracts are traditionally used in Ivory Coast, West Africa to treat bacterial infections caused by Escherichia coli (E. coli), and fungal infections caused by Candida albicans (C. albicans) and dermatophytes. Our working hypothesis was that the extract contains active ingredient(s) which can be isolated, identified and developed into useful antibacterial/antifungal agents for the treatment of opportunistic infections in patients with AIDS. We used the broth dilution and agar dilution methods. Specifically, we focused on E. coli and C. albicans and the effectiveness of the extracts was evaluated relative to those of standard antibacterial agent chloramphenicol and antifungal agent amphotericin B. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the water extract of C. alata against E. coli were 1.6 mg/ml and 60 mg/ml, respectively; corresponding data for chloramphenicol were 2 micrograms/ml and 10 micrograms/ml. Similarly, the MIC and minimum fungicidal concentration (MFC) for the extract against C. albicans were 0.39 mg/ml and 60 mg/ml in contrast to 0.58 micrograms/ml and 0.98 micrograms/ml for amphotericin B. From the dose-response curve plots, the extract had an IC50 of 31 mg/ml for E. coli and 28 mg/ml for C. albicans. The data suggest that C. alata extracts contain agent(s) which have therapeutic potential and might be useful if isolated and developed for the treatment of opportunistic infections of AIDS patients.     

Antibodies to the infective agents of opportunistic infections in blood of patients with hemoblastosis complicated with pneumonia

The examination of 112 hematological patients with diagnosed acute and chronic leucosis, lymphoma, myeloma, anemia, melanoma and other diseases revealed not a single subject among these examinees in whom no markers of opportunistic infections were detected. Low titers of antibodies to Pneumocystis carinii, cytomegalovirus (CMV), Epstein-Barr virus (EBV) were noted in 42%, 46.4% and 40.2% of examinees, respectively. Markers of acute diseases, such as class IgM, IgG antibodies in high titers, as well as P.carinii, CMV, EBV antigens, were detected in 37.5%, 30.4% and 22.3% of patients of a hematological hospital. In the group of comparison (donors) these figures were, respectively, 15.3%, 2.4% and 6.9%. The signs of monoinfection were detected in 11.6% (pneumocystosis), in 10.7% (CMV infection) and in 14.3% (EBV infection), while the markers of two infections, EBV infection and pneumocystosis, were detected in 9.8%, EBV and CMV infections in 11.6%, pneumocystosis and CMV infection in 14.3%; mixed contamination with all three infective agents was detected in 12.5% of the patients.     

566C80, an antimalarial hydroxynaphthoquinone with broad spectrum: experimental activity against opportunistic parasitic infections of AIDS patients.

Hydroxynaphthoquinone 566C80 was synthesised and initially developed as an antimalarial with potent activity against drug-resistant strains of the human malaria parasite, Plasmodium falciparum. Subsequent studies have revealed that in addition, this compound has experimental activity, both in vitro and in vivo, against Pneumocystis carinii and Toxoplasma gondii; the data obtained thus far for Cryptosporidium parvum are equivocal. Currently 566C80 is being assessed clinically not only against malaria, but also against P. carinii pneumonia, toxoplasmosis and cryptosporidiosis.     

Changes in activity of antioxidant enzymes and photosynthetic machinery during acclimatization of micropropagated Cassia alata L. plantlets

The stimulatory effect of thidiazuron (TDZ) has been investigated in shoot multiplication for a simple, efficient, rapid, and commercially applicable regeneration protocol of an important medicinal plant, Cassia alata. Furthermore, the effects of an increased photosynthetic photon flux density (PPFD) on photosynthesis, the functioning of the photosynthetic apparatus, and the response of the antioxidant enzymatic system were studied during the ex vitro establishment of micropropagated plantlets. Multiple shoots were induced by culturing nodal explants excised from an aseptic seedling on Murashige and Skoog (MS) medium supplemented with various concentrations (1.0, 2.5, 5.0, 7.5, or 10.0 μM) of TDZ for different treatment durations (2, 3, 4, or 6 wk). The highest number of shoots (17.9?±?0.3) and longest shoot length (4.6?±?0.1 cm) were achieved when explants were exposed to 5.0 μM TDZ for 4 wk and subsequently subcultured on growth regulator-free MS medium for 8 wk. In vitro rooting of isolated shoots was best achieved on full-strength MS medium containing 0.5 μM indole-3-butyric acid (IBA). The micropropagated shoots with well-developed roots were successfully established in pots containing Soilrite? followed by garden soil and grown in greenhouse with an 85% survival rate. During the acclimatization period, significant changes in the activity of the antioxidant enzymatic system were observed. An increase in superoxide dismutase (SOD) activity was measured throughout the acclimatization period. Likewise an upregulation of catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) enzyme activities were also observed. Pigment (chlorophyll a and b and carotenoids) content in ex vitro-formed leaves was significantly higher compared with those grown in vitro. These observed changes reflected the ability of plants to develop an antioxidant enzymatic defense system aiding in survival against oxidative stress and in reducing release of free radicals.     

Novel therapeutic agents for the treatment of gastroenteropancreatic neuroendocrine tumors

Neuroendocrine tumors (NET) are frequently diagnosed late and not amenable to curative surgery due to metastatic disease to the liver and lymph nodes. The disease is complex and heterogeneous given the various functionalities, distinct tumor growth patterns, and tumor spread upon diagnosis. Established therapies include somatostatin analogues, alpha-interferon, systemic chemotherapy, and loco-regional therapies of the liver. The availability of novel agents and expression of targets, such as growth factor receptors, different subtypes of somatostatin receptors, and the mammalian target of rapamycin (mTOR) have led to the exploration of different classes of drugs and offer new treatment opportunities in neuroendocrine tumors. This review provides an overview on novel drugs, focus on the impact of recently approved drugs on the management of NET disease, and outline future perspectives.     

Bisphosphonates: new therapeutic agents for the treatment of bone tumors

Bisphosphonates (BPs) have been used successfully for many years to reduce the skeletal complications associated with the benign and malignant bone diseases that are characterized by enhanced osteoclastic bone resorption. Until recently, it was thought that the clinical efficacy of BPs in the treatment of cancer patients with bone metastases was purely a result of the inhibition of osteoclast-mediated bone resorption. However, recent studies have demonstrated that BPs inhibit the growth, attachment and invasion of cancer cells in culture and promote their apoptosis. These results suggest that BPs are also anti-cancer agents, raising the possibility that BPs could inhibit cancer-cell colonization in visceral organs. However, results from clinical trials are conflicting, and whether BPs possess anti-cancer effects or not remains controversial.     

268例艾滋病合并机会性感染患者血液、体液培养结果分析

人类免疫缺陷病毒(human immunodeficiencyvirus,HIV)感染人体后造成机体免疫系统功能进行性下降,表现出各种机会性感染和/或肿瘤,称之为“获得性免疫缺陷综合征(acquired immunodefi-ciency syndrome,AIDS)”。本文总结分析了两年来268例AIDS合并机会性感染患者血液、体液等样     

In search of a treatment for Alzheimer's disease and potential immunonosuppresive therapeutic interventions

Alzheimer's disease (AD) is a serious neurodegenerative disease of aging. Recent projections of the dramatic increase in AD incidence worldwide by 2050 reveal its magnitude as a world-wide health crisis and underscore the urgent need to understand the etiology of AD in order to develop therapeutic interventions. A popular debate among scientists has traditionally pitted those in support of Beta amyloid protein as a causative factor ("Baptists") against others who implicate tau hyperphosphorylation ("Tauists"). Considering the significance of Beta amyloid protein and hyperphosphorlyated tau protein aggregates in AD pathology, this article delves into the nature of inflammation associated with these aggregates. Aspects of inflammation focus on microglia, resident immune cells of the CNS that are activated during AD inflammation and are known to play a significant role in pathogenesis. This article discusses the role of microglia, inflammation, and the immune response as a middle ground in the debate between the "Tauists" and the "Baptists" respective positions. It explores recent advances in immunotherapy and supports continued research in and use of immunosuppressive regimens as potential therapeutic interventions for AD.     

Cytologic evaluation of bronchoalveolar lavage specimens in immunosuppressed patients with suspected opportunistic infections

The role of bronchoalveolar lavage cytology in the diagnostic evaluation of immunosuppressed patients with suspected opportunistic pulmonary infections was evaluated by comparing two groups of patients who underwent fiberoptic bronchoscopy. Bronchoalveolar lavage specimens were compared with other available diagnostic techniques, including bronchial washings, bronchial brushings, transbronchial lung biopsies and open lung biopsy. Prior to the initiation of a protocol for bronchoalveolar lavage, a specific etiology for the pulmonary infiltrate using the above combined modalities was identified in 23 of 47 cases, for an overall diagnostic rate of 49%. The combined bronchial washings and brushings (cytologic procedures) identified a specific etiology in 9 of 47 (19%) of the cases. There were ten cases in which a cytologically identifiable organism (Pneumocystis, virus or fungus) was not present in the bronchial washings and brushings and one missed case of malignancy, for a false-negative rate of 23%. With the addition of the lavage technique and better sampling of the distal airways, a specific etiology for the pulmonary infiltrate was identified in 32 of 48 (67%) of the cases. This is comparable to the values of 40% to 65% cited in the literature for diagnosis of infectious disease by open lung biopsy. The lavage cytologic procedure identified a specific etiology in 22 of 48 (46%) of the cases, and the false-negative rate was reduced to 6%. With the excellent sampling of the bronchoalveolar lavage and the improved cytology results, the need for transbronchial or open lung biopsy has been eliminated in immunosuppressed patients with suspected opportunistic pulmonary infections. This allows these patients to be studied on an outpatient basis.     

Frequent infections of neutropenic pediatric patients and therapeutic modalities

Neutropenia, resulting from intensive chemotherapy is a common problem. The appearance of fever in neutropenic patients should always raise the suspicion of infection and should be followed by an intensive diagnostic evaluation and start of antibacterial treatment. The authors analyzed the association between isolated bacteria from blood cultures and the clinical background of all febrile episodes that occurred in neutropenic children in a two-year long period. Comparable to the international trends, our results suggest an increased prevalence of the Gram-positive organisms causing bacteriaemia. The clear majority of the isolated bacteria was coagulase-negativ Staphylococcus (cnS), which is a multiresistant strain, and sensitive only to the glycopeptide antibiotics. This latter fact can be a consequence of the frequent use of central venous catheters. The empirical therapy, the therapy used in microbiologically and clinically proved infections, and the supplementary and prophylactic methods of treatment are presented.     

Use of hydroxyapatite-coasted glass beads for preclinical testing of potential antiplaque agents.

Methods for rapid preclinical testing of antiplaque agents in vitro using hydroxyapatite (HT)-coated glass beads are described. The assays developed could reliably detect (i) prevention of growth in the culture fluid or on the HT surfaces, (ii) the effect of transient exposure of a bactericidal agent on the viability of cells in a preformed bacterial mat, (iii) reversible adsorption of a bactericidal agent on an HT surface, and (iv) the ability of an agent to inhibit adsorption of Streptococcus sanguis to an HT surface or to salivary proteins adsorbed to an HT surface.     

卡泊芬净联合复方磺胺甲噁唑治疗艾滋病合并肺孢子菌肺炎

目的探讨卡泊芬净联合复方磺胺甲噁唑(TMP-SMX)治疗艾滋病合并肺孢子菌肺炎(PCP)的疗效。方法回顾性总结分析9例艾滋病合并肺孢子菌肺炎的临床资料,包括临床特点及诊疗经过。结果 9例患者临床诊断PCP成立,经卡泊芬净联合TMP-SMX抗PCP治疗后,除1例死亡(老年患者合并慢性支气管炎病史)外,其余8例均得到满意疗效。结论卡泊芬净联合TMP-SMX治疗艾滋病合并PCP,可达到良好的治疗效果。     

Current strategies in the search for novel antiparasitic agents

The market for antiparasitic products comprises the largest segment for sales of livestock and companion-animal healthcare agents. Despite the availability of highly effective, broad-spectrum agents, there remains a need for safer, more convenient and more environmentally friendly products that will overcome the ever-present threat of resistance development. The very high cost of discovering and developing a new drug, especially for use in livestock, is reflected in the limited number of new classes of antiparasitic agent launched on the market. New strategies are being adopted to minimise the cost of discovering potential drug candidates by maximising the chance of identifying a useful target mechanism of action and by speeding the time to discover and optimise a lead structure. These rely heavily on new technologies in target identification, screen development and lead optimisation. Examples of these will be discussed and speculation made about the possible factors that could influence the future shape of antiparasitic control.     

HIV/AIDS患者机会性感染与CD4+ T淋巴细胞间的关联性

目的 研究人免疫缺陷病毒（HIV）感染者及艾滋病（AIDS）患者发生机会性感染的概率与自身CD4+ T淋巴细胞之间的关系,为HIV患者机会性感染的防治提供参考。方法 以2016年6月至2017年6月我院400例HIV患者为研究对象,回顾性分析不同CD4+T淋巴细胞计数HIV患者发生机会性感染的情况。结果 400例HIV患者发生机会性感染178例,总感染率为44.5%。CD4+T淋巴细胞计数≤50个/μL的患者机会性感染发生率（86.67%）最高,与其他各组比较差异有统计学意义（P<0.05）。随着CD4+ T淋巴细胞计数的减少,HIV患者机会性感染率升高。178例机会性感染者中,单一感染82例,2部位感染52例,3部位感染28例,4部位以上感染16例。感染病原体检测显示,细菌感染84例（47.19%）,结核杆菌感染36例（20.22%）,病毒感染30例（16.85%,包括巨细胞病毒感染18例、单纯疱疹病毒感染12例）,真菌感染77例（43.25%,包括假丝酵母感染35例,肺孢子菌感染20例,马尔尼菲青霉菌感染12例,新型隐球菌感染10例）,未明确病原体性质34例（19.10%）,复合感染多见。结论 CD4+ T淋巴细胞水平与HIV患者继发机会性感染的概率关系密切。HIV患者CD4+ T淋巴细胞水平的监测对其继发机会性感染的防控具有重要临床意义。