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1.
J Parasitol ; 107(5): 769-775, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34473291

ABSTRACT

The life cycle and ecology of the horsehair worm Chordodes morgani (Nematomorpha) in Nebraska remain unknown. To identify its definitive host, we installed a series of pitfall traps along 3 first-order streams at 4 sites: Elk Creek, Upper Elk Creek, Maple Creek, and West Oak Creek, all located northwest of Lincoln, Nebraska. In addition, we opportunistically hand-collected insects at these sites, including wood cockroaches (Parcoblatta virginica), and maintained them in the lab until they passed adult worms. Two of these field-collected wood cockroaches each yielded 1 adult worm, which was identified as C. morgani by microscopy, showing that P. virginica serves as a definitive host. Experimental infections of captive-reared Parcoblatta americana supported this result. The wood cockroach was found at all 3 creeks, but C. morgani was not found at West Oak Creek, suggesting that the definitive host does not limit the distribution of C. morgani. Physical properties of the streams were measured to examine how these properties influenced the distribution of the worm. Flow rate and pH differed between the 3 sites where C. morgani was found and the West Oak Creek site, suggesting an important role for these abiotic factors in the distribution of this horsehair worm species.


Subject(s)
Arthropods/parasitology , Parasites/physiology , Analysis of Variance , Animals , Host-Parasite Interactions , Hydrogen-Ion Concentration , Life Cycle Stages , Nebraska , Parasites/growth & development , Periplaneta/parasitology , Rivers/chemistry , Seasons , Tropical Climate
2.
Bioconjug Chem ; 29(10): 3362-3376, 2018 10 17.
Article in English | MEDLINE | ID: mdl-30169965

ABSTRACT

The impact of influenza virus infection is felt each year on a global scale when approximately 5-10% of adults and 20-30% of children globally are infected. While vaccination is the primary strategy for influenza prevention, there are a number of likely scenarios for which vaccination is inadequate, making the development of effective antiviral agents of utmost importance. Anti-influenza treatments with innovative mechanisms of action are critical in the face of emerging viral resistance to the existing drugs. These new antiviral agents are urgently needed to address future epidemic (or pandemic) influenza and are critical for the immune-compromised cohort who cannot be vaccinated. We have previously shown that lipid tagged peptides derived from the C-terminal region of influenza hemagglutinin (HA) were effective influenza fusion inhibitors. In this study, we modified the influenza fusion inhibitors by adding a cell penetrating peptide sequence to promote intracellular targeting. These fusion-inhibiting peptides self-assemble into ∼15-30 nm nanoparticles (NPs), target relevant infectious tissues in vivo, and reduce viral infectivity upon interaction with the cell membrane. Overall, our data show that the CPP and the lipid moiety are both required for efficient biodistribution, fusion inhibition, and efficacy in vivo.


Subject(s)
Antiviral Agents/pharmacology , Cell-Penetrating Peptides/pharmacology , Influenza A virus/drug effects , Membrane Fusion/drug effects , Administration, Intranasal , Amino Acid Sequence , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Biological Availability , Cell Membrane/metabolism , Cell-Penetrating Peptides/chemistry , Endocytosis , Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Humans , Immunocompromised Host , Nanoparticles/chemistry , Sigmodontinae , Viral Proteins/chemistry , tat Gene Products, Human Immunodeficiency Virus/chemistry
3.
J Virol ; 91(1)2017 Jan 01.
Article in English | MEDLINE | ID: mdl-27733647

ABSTRACT

Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE: Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides.


Subject(s)
Hemagglutinins, Viral/immunology , Measles Vaccine/administration & dosage , Measles virus/drug effects , Measles/prevention & control , Nanoparticles/administration & dosage , Peptides/immunology , Viral Fusion Proteins/immunology , Administration, Intranasal , Amino Acid Sequence , Animals , Brain/drug effects , Brain/immunology , Cholesterol/chemistry , Female , Half-Life , Hemagglutinins, Viral/chemistry , Humans , Lung/drug effects , Lung/immunology , Male , Measles/immunology , Measles/mortality , Measles/virology , Measles Vaccine/chemical synthesis , Measles virus/chemistry , Measles virus/immunology , Nanoparticles/chemistry , Peptides/chemical synthesis , Sigmodontinae , Survival Analysis , Viral Fusion Proteins/chemistry , Virus Internalization/drug effects
4.
Braz J Med Biol Res ; 37(10): 1551-6, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15448877

ABSTRACT

The maximal lactate steady state (MLSS) is the highest blood lactate concentration that can be identified as maintaining a steady state during a prolonged submaximal constant workload. The objective of the present study was to analyze the influence of the aerobic capacity on the validity of anaerobic threshold (AT) to estimate the exercise intensity at MLSS (MLSS intensity) during cycling. Ten untrained males (UC) and 9 male endurance cyclists (EC) matched for age, weight and height performed one incremental maximal load test to determine AT and two to four 30-min constant submaximal load tests on a mechanically braked cycle ergometer to determine MLSS and MLSS intensity. AT was determined as the intensity corresponding to 3.5 mM blood lactate. MLSS intensity was defined as the highest workload at which blood lactate concentration did not increase by more than 1 mM between minutes 10 and 30 of the constant workload. MLSS intensity (EC = 282.1 +/- 23.8 W; UC = 180.2 +/- 24.5 W) and AT (EC = 274.8 +/- 24.9 W; UC = 187.2 +/- 28.0 W) were significantly higher in trained group. However, there was no significant difference in MLSS between EC (5.0 +/- 1.2 mM) and UC (4.9 +/- 1.7 mM). The MLSS intensity and AT were not different and significantly correlated in both groups (EC: r = 0.77; UC: r = 0.81). We conclude that MLSS and the validity of AT to estimate MLSS intensity during cycling, analyzed in a cross-sectional design (trained x sedentary), do not depend on the aerobic capacity.


Subject(s)
Anaerobic Threshold/physiology , Bicycling/physiology , Lactic Acid/blood , Oxygen Consumption/physiology , Cross-Sectional Studies , Humans , Male , Time Factors
5.
J Bras Ginecol ; 96(8): 391-7, 1986 Aug.
Article in Portuguese | MEDLINE | ID: mdl-12281066

ABSTRACT

PIP: Contraceptive hormonal injectable action of medroxy-progesterone acetate ciprionate estradiol (MPACE) in the reproductive system of female rats was studied. The female rats were selected in 2 groups: A and B, castrated and non castrated, respectively, and according to dose numbers in 6 subgroups: A0, A1, A2, A3, A4, A5 and B0, B1, B2, B3, B4, B5. Karyometric studies of nuclei from uterine epithelial tunica mucosa endometrial glands, myometrium, exocervix and vaginal epithelium were made. For each subgroup females were selected and 3 slides analyzed for each 1, which means 9 observations per subgroup. From uterine epithelial tunica mucosa, endometrial glands, and myometrium kariometric, 20 nuclei were measured per slide, in a total of 60. When dealing with vaginal and exocervical epithelia, 120 nuclei were measured as both are stratified epithelia. Karyometric studies were made in 15,120 nuclei and the results statistically analyzed. Nearly a 2-fold increase in nuclear volume was observed in female rats at the estrual phase as compared with castrated female controls. A higher significant MPACE effect was found in cells covering uterine epithelial tunica mucosa, endometric glands, and myometrium. The MPACE action on the exocervix and vaginal cells was not significant. As statistically assessed, the MPACE combination showed a predominance of the estrogenic portion with an increase of nuclear volumes but this action was balanced by the progestagenic fraction, as mitoses were unusual.^ieng


Subject(s)
Animals, Laboratory , Contraception , Contraceptive Agents, Female , Disease , Endometrium , Evaluation Studies as Topic , Family Planning Services , Genitalia, Female , Hormones , Injections , Medroxyprogesterone Acetate , Reproductive Control Agents , Research , Urogenital System , Uterus , Biology , Contraceptive Agents , Economics , Endocrine System , Genitalia , Physiology , Technology
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