Current issues in the pathogenesis and management of HIV-related tuberculosis.
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Anti-HIV Agents↗
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Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases.
The inflammatory bowel diseases (IBDs) are characterized by intestinal inflammation of unknown etiology. Two distinct disorders, Crohn's disease and ulcerative colitis, have been identified. Three theories of IBD etiology are currently under consideration: 1) reaction to a persistent intestinal infection, 2) existence of a defective mucosal barrier to luminal antigens, and 3) a dysregulated host immune response to ubiquitous antigens. In each of these theories, either pathogenic or resident luminal bacteria constantly stimulate the mucosal and systemic immune systems to perpetuate the inflammatory cascade. Chronicity of inflammation results from an interaction of the persistent stimulus of microbial antigens with genetically determined host susceptibility factors that determine the individual's immune response or mucosal barrier function. The pathogenesis of IBD involves a series of steps, beginning with the breach of the intestinal mucosal barrier by infectious agents or toxins. The defective barrier exposes lamina propria immune cells to the continual presence of resident luminal bacteria, bacterial products, or dietary antigens, which perpetuates the inflammatory cascade. Many immunoregulatory abnormalities are noted in IBD, including the ratio of proinflammatory to immunosuppressive cytokines, selective activation of T(H) lymphocyte subsets, and abnormalities in epithelial antigen presentation. When activated during the initial inflammatory process, macrophages and T lymphocytes secrete a host of cytokines, which recruit other inflammatory cell types, thereby continuing the process. Tissue injury is the net result of the soluble products of the activated inflammatory cells. Knowledge of the pathogenesis in IBD suggests that the ultimate goals of therapy should be to block the proinflammatory mediators toward the proximal, rather than the distal, end of the cascade, to decrease the constant antigenic drive of luminal bacteria, and to correct the dysregulated immune response.
Chronic Disease↗
Practical issues regarding the use of antiretroviral therapy for HIV infection.
With the recent development of potent new antiretroviral therapies, the management of HIV infection has become increasingly complex. There are now 12 antiretroviral drugs approved for use in the management of HIV infection, with several more in the advanced stages of clinical development. Staying current with this rapidly changing area of medicine is a challenge to clinicians caring for HIV-infected patients. This review provides an overview of HIV pathogenesis and discusses the basic principles of therapy. These principles, developed recently by the U.S. Department of Health and Human Services, provide a practical framework to rapidly incorporate new developments into clinical practice. Each of the three classes of antiretroviral therapies is then explained, focusing on the practical management of side effects, drug interactions, and viral resistance. The antiviral activity and clinical efficacy of each therapeutic class is reviewed, with an emphasis on applying current results to clinical decision making. Finally, recently published treatment guidelines are reviewed.
Anti-HIV Agents↗
Macrolide antibiotics.
The macrolides remain excellent antibiotics for many infections particularly those involving intracellular and/or respiratory pathogens. Erythromycin is still an effective drug for many acute orofacial infections. The newer macrolides, azithromycin and clarithromycin, should also prove efficacious although there is very little current data on their use in orofacial infections. They have the advantages over erythromycin of less GI toxicity, higher tissue concentrations, greater gram-negative spectrum, and once or twice daily dosing for better patient compliance. Macrolide concentration in inflammatory cells and transport to the site of infection is a distinct advantage over other antibiotics. Both erythromycin and clarithromycin are associated with significant drug interactions but azithromycin is devoid of such potential toxicity. Azithromycin is less effective against gram-negative cocci than erythromycin and clarithromycin and attains very high tissue concentrations for a very long time, but whether either of these characteristics is clinically significant for orofacial infections is presently unknown.
Acute Disease↗
Update on antibiotics in dentistry. Interview by Phillip Bonner.
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Antibiotic Prophylaxis↗
["Short-term" or "long term care" with antibiotics].
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Anti-Bacterial Agents↗
[Advances in the diagnosis and treatment of infections caused by herpesvirus and JC virus].
During the last two years important advances in the diagnosis and treatment of cytomegalovirus (CMV) disease have occurred. Several studies have suggested that biologic markers of CMV viremia (PCR, branched DNA and pp65 antigenemia) might be useful both to stratify the risk of developing CMV disease and to follow the response of CMV retinitis to therapy. It has been shown that patients who are plasma CMV PCR positive have a risk of developing CMV disease three times higher than patients who are plasma CMV PCR negative. In addition, for each log10 increase of the CMV viral load there is a 3-fold higher risk of developing CMV disease. Currently, therapeutic options for induction treatment of CMV retinitis (CMVR) are: i.v. ganciclovir (GCV), i.v. foscarnet, i.v. cidofovir or GCV intraocular implant combined with oral GCV. For maintenance therapy options are: i.v. GCV (3, 5 or 7 days per week), oral GCV (only for peripheral retinitis), i.v. foscarnet (daily), i.v. cidofovir (biweekly) and GCV intraocular implant (replaced every 6-8 months) combined with oral GCV. There is currently enough evidence to allow the diagnosis of progressive multifocal leukoencephalopathy (PML) based on the finding of JC virus DNA in CSF by PCR. There are still no drugs with proven clinical efficacy against JC virus but the possibility that HAART treatments might improve the control of this disease appear promising.
AIDS-Related Opportunistic Infections↗
[Diagnosis and treatment of mycobacterial infections in patients with HIV/AIDS].
Mycobacterial infection remains as a frequent complication associated to HIV infection. Although the widespread use of HAART has intensely decreased incidence of disseminated Mycobacterium avium (MAC) infection, it does not seem that it has affected tuberculosis occurrence so intensely. In spite of the intense search of new methods of rapid diagnosis, in the clinical practice the diagnosis of the mycobacterial illnesses continues based on culture, although the appearance of new media has allowed to shorten the time of growth. The combination of isoniazid (INH), rifampin (RIF) and pirazinamide (PZ) (with ethambutol [ETB] when primary resistance to INH is higher than 4%), remains as the elective treatment for tuberculosis in HIV infected patients. Due to the interaction between RIF and some antiretovirals drugs, such as proteasa inhibitors, a change in the usual regimens could be necessary. Combinations without RIF or antiretroviral therapy with drugs not interacting with RIF (nucleosides, ritonavir or nevirapin) have been suggested. The emergence of strains of Mycobacterium tuberculosis resistant to the antituberculosis drugs, the lack of adherence to treatment, and the frequency of adverse events hinders even more the control of the tuberculosis and they demand a narrow follow up of these patients. The treatment of the disseminated infection by MAC has improved in the last years with the generalization of the combinations including macrolides as claritromicin or azitromicin with ETB. The doubt persists about what combination is more effective, although like in other opportunists infections associated with a severe immunodeficiency, using antiretrovirals combinations that enhance the immune system could be a fundamental therapeutic approach.
AIDS-Related Opportunistic Infections↗
State of the art: antiretroviral and prophylactic treatments in HIV/AIDS.
HIV results in a continual and progressive pathological attack on the human immune system. This attack on the immune system can be altered with combination antiretroviral agents that interrupt the HIV life-cycle. There are three classes of approved antiretroviral agents: nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors. The progressive deterioration of the patient's immune system by HIV infection increases the likelihood of developing opportunistic infections. Primary measures that can be taken to prevent the development of opportunistic infections are preventing exposure to the microorganisms in the environment and maintaining a competent immune system using antiretroviral therapy through prophylactic agents specific to opportunistic infections.
AIDS-Related Opportunistic Infections↗
DRINK: a biogeochemical source term model for low level radioactive waste disposal sites.
Interactions between element chemistry and the ambient geochemistry play a significant role in the control of radionuclide migration in the geosphere. These same interactions influence radionuclide release from near surface, low level radioactive waste, disposal sites once physical containment has degraded. In situations where LLW contains significant amounts of metal and organic materials such as cellulose, microbial degradation in conjunction with corrosion can significantly perturb the ambient geochemistry. These processes typically produce a transition from oxidising to reducing conditions and can influence radionuclide migration through changes in both the dominant radionuclide species and mineral phases. The DRINK (DRIgg Near field Kinetic) code is a biogeochemical transport code designed to simulate the long term evolution of the UK low level radioactive waste disposal site at Drigg. Drigg is the UK's principal solid low level radioactive waste disposal site and has been receiving waste since 1959. The interaction between microbial activity, the ambient geochemistry and radionuclide chemistry is central to the DRINK approach with the development of the ambient pH, redox potential and bulk geochemistry being directly influenced by microbial activity. This paper describes the microbial aspects of the code, site data underpinning the microbial model, the microbiology/chemistry interface and provides an example of the code in action.
Environmental Microbiology↗
Rhizosphere feedbacks in elevated CO(2).
Understanding rhizosphere processes in relation to increasing atmospheric CO(2) concentrations is important for predicting the response of forest ecosystems to environmental changes, because rhizosphere processes are intimately linked with nutrient cycling and soil organic matter decomposition, both of which feedback to tree growth and soil carbon storage. Plants grown in elevated CO(2) substantially increase C input to the rhizosphere. Although it is known that elevated CO(2) enhances rhizosphere respiration more than it enhances root biomass, the fate and function of this extra carbon input to the rhizosphere in response to elevated CO(2) are not clear. Depending on specific plant and soil conditions, the increased carbon input to the rhizosphere can result in an increase, a decrease, or no effect on soil organic matter decomposition and nutrient mineralization. Three mechanisms may account for these inconsistent results: (1) the "preferential substrate utilization" hypothesis; (2) the "priming effect" hypothesis; and (3) the "competition" hypothesis, i.e., competition for mineral nutrients between plants and soil microorganisms. A microbial growth model is developed that quantitatively links the increased rhizosphere input in response to elevated CO(2) with soil organic matter decomposition. The model incorporates the three proposed mechanisms, and simulates the complexity of the rhizosphere processes. The model also illustrates mechanistically the interactions among nitrogen availability, substrate quality, and microbial dynamics when the system is exposed to elevated CO(2).
Journal Article↗
Effect of roundup ultra on microbial activity and biomass from selected soils.
Herbicides applied to soils potentially affect soil microbial activity. The quantity and frequency of Roundup Ultra [RU; N-(phosphonomethyl)glycine; Monsanto, St. Louis, MO] applications have escalated with the advent of Roundup-tolerant crops. The objective of this study was to determine the effect of Roundup Ultra on soil microbial biomass and activity across a range of soils varying in fertility. The isoproplyamine salt of glyphosate was applied in the form of RU at a rate of 234 mg active ingredient kg(-1) soil based on an assumed 2-mm glyphosate-soil interaction depth. Roundup Ultra significantly stimulated soil microbial activity as measured by C and N mineralization, as well as soil microbial biomass. Cumulative C mineralization as well as mineralization rate increased above background levels for all soils tested with addition of RU. There were strong linear relationships between C and N mineralized, as well as between soil microbial C and N (r2 = 0.96 and 0.95, respectively). The slopes of the relationships with RU addition approximated three. Since the isopropylamine salt of glyphosate has a C to N ratio of 3:1, the data strongly suggest that RU was the direct cause of the enhanced microbial activity. An increase in the C mineralization rate occurred the first day following RU addition and continued for 14 d. Roundup Ultra appeared to be rapidly degraded by soil microbes regardless of soil type or organic matter content, even at high application rates, without adversely affecting microbial activity.
Biomass↗
Galectins as immunoregulators during infectious processes: from microbial invasion to the resolution of the disease.
Recent evidence has implicated galectins, a family of evolutionarily conserved carbohydrate-binding proteins, as regulators of immune cell homeostasis and host-pathogen interactions. Galectins operate at different levels of innate and adaptive immune responses, by modulating cell survival and cell activation or by influencing the Th1/Th2 cytokine balance. Furthermore, galectins may contribute to host-pathogen recognition and may serve as receptors for specific interactions of pathogens with their insect vectors. Here we will explore the influence of galectins in immunological processes relevant to microbial infection and will summarize exciting recent work related to the specific interactions between galectins and their glycoconjugate ligands as critical determinants of pathogen recognition. Understanding the role of galectin-sugar interactions during the course of microbial infections might contribute to defining novel targets for disease prevention and immune intervention.
Animals↗
High temperature ecosystems and their chemical interactions with their environment.
Phototrophic thermal ecosystems consist of microbial mats whose composition is largely determined by water temperature, dissolved oxygen, sulfide and pH. Mats exposed to sunlight consist of an upper zone of phototrophic bacteria and cyanobacteria and an undermat of heterotrophic bacteria. There is little or no net accumulation of reduced carbon and a quasi-equilibrium is established between the synthesis and oxidation of reduced carbon. The flux of carbon and other metabolites induces chemical change in the interstitial water which may assist the deposition of hydrothermal minerals. Uptake of carbon dioxide by phototrophs is favourable to calcium carbonate (travertine) deposition. Thermal systems also contain a range of chemolithotrophs and sulfate reducers potentially capable of depositing carbonate. Acid production by sulfate reducers may have the ability to precipitate silica from alkaline thermal waters but has not yet been demonstrated in vivo. Deposition of thermal ochre is also possible via bacterial oxidation of reduced iron and manganese. It appears that bacteria play a minor role in the deposition of hydrothermal minerals through chemical interaction. However, they may play a more important physical role by providing a large surface are suitable for mineral nucleation. If hydrothermal deposits occur on Mars, the distribution of travertine is likely to be restricted if there is a lack of pre-existing sedimentary carbonate. Less biologically interactive deposits of silica and ochre may predominate.
Archaea↗
[Unnecessary use of antibiotics. Reaction to 'Interaction of diet and veterinary drugs'].
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Animal Feed↗
Exploring the ecological drivers of bacteriophage diversity and functional viral potential in the skin of the axolotl Ambystoma altamirani.
Bacteriophages play important roles in shaping microbial community dynamics across diverse environments. In the amphibian skin, most microbiome studies have focused on bacteria and their interactions with the fungus Batrachochytrium dendrobatidis (Bd), leaving other microbial components, including viruses, largely unexplored. Here, we present the first characterization of the viral community in the amphibian skin microbiome, focusing on ecological drivers of bacteriophage diversity and functional potential in the axolotl Ambystoma altamirani. Using public shotgun metagenomes, we found that the viral fraction was dominated by bacteriophages of the class Caudoviricetes. Bacteriophage diversity was significantly associated with local physicochemical parameters at the time of sampling, and showed a strong positive correlation with bacterial diversity, whereas no significant associations were detected with the presence of Bd. In addition, seasonality influenced the composition and properties of bacteria-bacteriophage co-abundance networks. Functional annotation of assembled bacteriophage sequences revealed a diverse functional potential, including putative auxiliary metabolic genes, superinfection exclusion, toxin-antitoxin, and virulence factors. Overall, these findings highlight the ecological relevance of bacteriophages in amphibian skin microbiomes and underscore the need for further studies on their role in the amphibian host's health.
Animals↗
T helper cell-dependent, microbial superantigen-induced murine B cell activation: polyclonal and antigen-specific antibody responses.
Microbial superantigens (SA), bound to human B cell surface MHC class II molecules, have been shown to promote direct, "cognate" interaction with SA-reactive autologous Th cells, resulting in polyclonal Ig production. To investigate the potential for microbial SA to support Th cell-dependent, Ag-specific antibody responses, we have extended our studies to the murine system. BALB/c Th cell lines (TCL), specific for either the Mycoplasma arthritis-derived SA or the Staphylococcus aureus-derived toxic shock syndrome toxin-1) were generated. These TCL cells are SA-specific, functionally noncross-reactive, and utilize distinct TCR V beta gene families. Coculture of SA-reactive TCL cells and syngeneic B cells bearing the relevant SA results in B cell proliferation and polyclonal IgM and IgG production. In contrast, Ag-specific (SRBC-specific) antibody-forming cells are only generated in cultures that also contain SRBC. Thus, microbial SA-mediated Th-B cell interactions induce both polyclonal B cell activation and provide selective help for the proliferation and/or differentiation of B cells that have encountered specific Ag. In additional studies, we determined that the in vivo administration of toxic shock syndrome toxin-1 to young, athymic (nude) BALB/c mice results in SA binding to splenic B cells, rendering these B cells effective stimulators of and targets for SA-reactive helper TCL cells. Taken together, these results demonstrate that microbial SA mediate productive Th-B cell interactions analogous to those that occur during allospecific Th-B cell interactions in vitro and GVHD in vivo. These findings are consistent with the hypothesis that microbial SA represent environmental factors that may trigger autoimmune disease in the genetically susceptible host.
Animals↗
Effect of fluorochromes on bacterial surface properties and interaction with granular media.
Simple, efficient, and safe tagging methods are desired in short-term microbial transport studies such as in the study of filtration systems for water and wastewater treatment. Suitability of selected fluorochromes as bacterial tagging agents in transport studies was evaluated on the basis of stability of stained cells and the effect of staining on bacterial surface characteristics and interaction with granular media. Surface properties were characterized by zeta potential and microbial adhesion to hydrocarbons. The effect of staining on interactions between bacteria and porous media was evaluated in terms of removal of bacteria in batch adsorption tests using sand coated with aluminum hydroxide to enhance adsorption. The DNA-specific fluorochrome 4',6-diamidino-2-phenylindole (DAPI) had generally negligible effects on bacterial surface properties and interaction with sand, as indicated in batch adsorption tests using pure cultures (Escherichia coli or Acinetobacter sp.) and wastewater bacteria. Cells stained with DAPI were stable for 48 h at 4 or 20 degrees C. Other nucleic acid fluorochromes tested had different but significant effects on bacterial cells and produced less stable fluorescence. Since transport through porous media is modulated by surface properties, it may be concluded based on these results that the choice of fluorochromes is critical in microbial transport studies. DAPI appeared to be a promising tagging agent. Time dependence of fluorescence of stained cells may limit the use of fluorochrome-tagged cells in long-term transport studies.
Acinetobacter↗