Quantitative and Qualitative Analyses of the Cell Death Process in Candida albicans Treated by Antifungal Agents

The death process of Candida albicans was investigated after treatment with the antifungal agents flucytosine and amphotericin B by assessing morphological and biophysical properties associated with cell death. C. albicans was treated varying time periods (from 6 to 48 hours) and examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM). SEM and AFM images clearly showed changes in morphology and biophysical properties. After drug treatment, the membrane of C. albicans was perforated, deformed, and shrunken. Compared to the control, C. albicans treated with flucytosine was softer and initially showed a greater adhesive force. Conversely, C. albicans treated with amphotericin B was harder and had a lower adhesive force. In both cases, the surface roughness increased as the treatment time increased. The relationships between morphological changes and the drugs were observed by AFM clearly; the surface of C. albicans treated with flucytosine underwent membrane collapse, expansion of holes, and shrinkage, while the membranes of cells treated with amphotericin B peeled off. According to these observations, the death process of C. albicans was divided into 4 phases, CDP0, CDP1, CDP2, and CDP4, which were determined based on morphological changes. Our results could be employed to further investigate the antifungal activity of compounds derived from natural sources

A Virulent Wolbachia Infection Decreases the Viability of the Dengue Vector Aedes aegypti during Periods of Embryonic Quiescence

A new approach for dengue control has been proposed that relies on life-shortening strains of the obligate intracellular bacterium Wolbachia pipientis to modify mosquito population age structure and reduce pathogen transmission. Previously we reported the stable transinfection of the major dengue vector Aedes aegypti with a life-shortening Wolbachia strain (wMelPop-CLA) from the vinegar fly Drosophila melanogaster. Here, we report a further characterization of the phenotypic effects of this virulent Wolbachia infection on several life-history traits of Ae. aegypti. Minor costs of wMelPop-CLA infection for pre-imaginal survivorship, development and adult size were found. However, we discovered that the wMelPop-CLA infection dramatically decreased the viability of desiccated Ae. aegypti eggs over time. Similarly, the reproductive fitness of wMelPop-CLA infected Ae. aegypti females declined with age. These results reveal a general pattern associated with wMelPop-CLA induced pathogenesis in this mosquito species, where host fitness costs increase during aging of both immature and adult life-history stages. In addition to influencing the invasion dynamics of this particular Wolbachia strain, we suggest that the negative impact of wMelPop-CLA on embryonic quiescence may have applied utility as a tool to reduce mosquito population size in regions with pronounced dry seasons or in regions that experience cool winters

Papillary renal cell carcinoma with metastatic laparoscopic port site and vaginal involvement: a case report

10.1186/1752-1947-5-131Journal of Medical Case Reports513

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

The Endosymbiotic Bacterium Wolbachia Induces Resistance to Dengue Virus in Aedes aegypti

Genetic strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases. The endosymbiotic bacterium Wolbachia has long been promoted as a potential vehicle for introducing disease-resistance genes into mosquitoes, thereby making them refractory to the human pathogens they transmit. Given the large overlap in tissue distribution and intracellular localization between Wolbachia and dengue virus in mosquitoes, we conducted experiments to characterize their interactions. Our results show that Wolbachia inhibits viral replication and dissemination in the main dengue vector, Aedes aegypti. Moreover, the virus transmission potential of Wolbachia-infected Ae. aegypti was significantly diminished when compared to wild-type mosquitoes that did not harbor Wolbachia. At 14 days post-infection, Wolbachia completely blocked dengue transmission in at least 37.5% of Ae. aegypti mosquitoes. We also observed that this Wolbachia-mediated viral interference was associated with an elevated basal immunity and increased longevity in the mosquitoes. These results underscore the potential usefulness of Wolbachia-based control strategies for population replacement

Disease burden and related medical costs of rotavirus infections in Taiwan

BACKGROUND: The disease burden and associated medical costs of rotavirus infections in inpatient and outpatient sectors in Taiwan were examined in anticipation of the availability of new rotavirus vaccines. METHODS: The yearly national case number and medical costs for all for inpatients and outpatients with acute gastroenteritis (AGE) were extracted from the Bureau of National Health Insurance database in Taiwan according to ICD-9-CM codes. A retrospective study was also performed using records of children with AGE seen at three hospitals in Taiwan in 2001 to identify laboratory confirmed rotavirus infection cases. The annual incidence and related medical costs of AGE due to rotavirus infection were then estimated. RESULTS: Children <5 years old comprised 83.6% of inpatient and 62.0% of outpatient pediatric AGE cases in Taiwan in 2001. Rotavirus was the most common agent detected among AGE patients in this age group in the three hospitals, and was detected in 32.9% (221/672) of inpatient and 24% (23/96) of outpatient stool specimens tested for microbial etiologies. An estimated 277,400 to 624,892 cases of rotavirus infections sought medical care in Taiwan in 2001, equaling one in 2 to 5 children <5 years old required medical care due to rotavirus infection. The incidence of hospitalization due to rotavirus infections was 1,528–1,997/100,000 for children <5 years old. The total associated medical costs due to rotavirus infection were estimated at US $10–16 millions in Taiwan in 2001. Although the per-capita medical cost of rotavirus infection was lower in Taiwan than in the United States or Hong Kong, the personal economic burden was similar among the three places when normalized for gross national incomes per capita. CONCLUSION: Infections caused by rotavirus constitute an important human and economic burden among young children in Taiwan. A safe and effective vaccine is urgently needed

A Review of Metallothionein Isoforms and their Role in Pathophysiology

The Metallothionein (MT) is a protein which has several interesting biological effects and has been demonstrated increase focus on the role of MT in various biological systems in the past three decades. The studies on the role of MT were limited with few areas like apoptosis and antioxidants in selected organs even fifty years after its discovery. Now acknowledge the exploration of various isoforms of MT such as MT-I, MT-II, MT-III and MT-IV and other isoforms in various biological systems

Treatment of Late Stage Disease in a Model of Arenaviral Hemorrhagic Fever: T-705 Efficacy and Reduced Toxicity Suggests an Alternative to Ribavirin

A growing number of arenaviruses are known to cause viral hemorrhagic fever (HF), a severe and life-threatening syndrome characterized by fever, malaise, and increased vascular permeability. Ribavirin, the only licensed antiviral indicated for the treatment of certain arenaviral HFs, has had mixed success and significant toxicity. Since severe arenaviral infections initially do not present with distinguishing symptoms and are difficult to clinically diagnose at early stages, it is of utmost importance to identify antiviral therapies effective at later stages of infection. We have previously reported that T-705, a substituted pyrazine derivative currently under development as an anti-influenza drug, is highly active in hamsters infected with Pichinde virus when the drug is administered orally early during the course of infection. Here we demonstrate that T-705 offers significant protection against this lethal arenaviral infection in hamsters when treatment is begun after the animals are ill and the day before the animals begin to succumb to disease. Importantly, this coincides with the time when peak viral loads are present in most organs and considerable tissue damage is evident. We also show that T-705 is as effective as, and less toxic than, ribavirin, as infected T-705-treated hamsters on average maintain their weight better and recover more rapidly than animals treated with ribavirin. Further, there was no added benefit to combination therapy with T-705 and ribavirin. Finally, pharmacokinetic data indicate that plasma T-705 levels following oral administration are markedly reduced during the latter stages of disease, and may contribute to the reduced efficacy seen when treatment is withheld until day 7 of infection. Our findings support further pre-clinical development of T-705 for the treatment of severe arenaviral infections

Human Probing Behavior of Aedes aegypti when Infected with a Life-Shortening Strain of Wolbachia

Mosquitoes transmit diseases when they are actively searching for a source of blood. This so called probing behavior comprises the “searching” time, the beginning of the feeding process until the first sign of blood can be seen within the insect body. The manipulation of this behavior can have important consequences for the mosquito's ability to transmit pathogens, such as dengue virus or Plasmodium. In this study we examined the probing behavior of the main vector of dengue viruses, Aedes aegypti, when infected with an intracellular bacterium, Wolbachia pipientis. This bacterium alters the probing behavior of older mosquitoes such that they take longer to find a feeding site and longer to imbibe blood, which may make them more susceptible to human defense responses. The bacterium appears to reduce mosquito feeding success by preventing the mosquito from successfully inserting its stylet into human skin. The old age onset of reduced mosquito feeding success due to Wolbachia could selectively promote a reduction in dengue transmission