scholarly journals The Biological Significance of Haemoglobin in Nematode Parasites II. The Properties of the Haemoglobins as Studied in Living Pabasites

1949 ◽  
Vol 2 (4) ◽  
pp. 399 ◽  
Author(s):  
WP Rogers
Keyword(s):  
Oxygen Tension ◽  
Haemonchus Contortus ◽  
Biological Significance ◽  
Water Soluble ◽  
Nematode Parasites

In the parasites examined, the amounts of water-soluble haematin compounds, of which haemoglobin formed the large part, varied considerably; Nippo$rongylus murls contained about 6 mg. (as haematin) per g. dry wt. of tissue, Nematodirus spp. and Haemonchus contortus about 0.8 mg. per g. dry wt. Evidence is presented which indicates that the haemoglobin of Nippo$rongylus muris may be oxygenated in vivo, at least sometimes. The haemoglobin in the living parasites was easily oxygenated and deoxygenated; when the oxygen tension in the medium surrounding the parasites in vitro at 37�C. fell below about 13 mm. of mercury (Nippostrongylus muris) or 9 mm. of mercury (Haemonchus contortus and Nematodirus spp.) the oxyhaemoglobin became deoxygenated.

scholarly journals Characterization of a Rhodanese Homologue from Haemonchus Contortus and its Immune-Modulatory Effects on Goat Immune Cells in Vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Parasitic Nematodes ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Suppression and modulation of the immune response of the host by nematode parasites have been reported widely. Rhodaneses or thiosulfate: cyanide sulfurtransferases are present in a wide range of organisms, such as archea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homology could bind by goat peripheral blood mononuclear cells (PBMCs) in vivo.Results: In the present study, we cloned and produced recombinant rhodanese protein originated from Haemonchus contortus (rHCRD), which was one of the parasitic nematodes of small ruminants. The effect of this protein on modulating the immunity of goat PBMC and monocyte was studied in the current work. The predominant localization of the natural HCRD protein was verified as the bowel wall and body surface of worms, according to the immunohistochemical tests. It was proved in this study that the serum produced by artificially infecting goats with H. contortus successfully recognized rHCRD which conjugated goat PBMCs. The rHCRD was co-incubated with goat PBMCs to observe the immunomodulatory effect on proliferation, apoptosis and secretion of cytokines exerted by HCRD. The results showed that the interaction of rHCRD suppressed proliferation of goat PBMCs stimulated by ConA but did not induce the apoptosis of goat PBMCs. After rHCRD exposure, the production of TNF-α and IFN-γ were significantly decreased, however, it significantly increased the secretion of IL-10 and TGF-β1 in goat PBMCs. Phagocytotic assay by FITC-dextran internalization showed that rHCRD inhibited the phagocytosis of goat monocytes. Moreover, rHCRD could down-regulate the expression of MHC-II on goat monocytes in a dose-dependent manner. Conclusions: These discoveries proposed a possible target as immunomodulator, which was potentially beneficial to illuminate the interaction between parasites and hosts in the molecular level and hunt for innovative protein species as candidate targets of drug and vaccine.

scholarly journals Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Mhc I ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD downregulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression.Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

scholarly journals On The Relative Importance of Aerobic Metabolism in Small Nematode Parasites of the Alimentary Tract II. the Utilization of Oxygen at Low Partial Pressures by Small Nematode Parasites of the Alimentary Tract

1949 ◽  
Vol 2 (2) ◽  
pp. 166 ◽  
Author(s):  
WP Rogers
Keyword(s):  
Small Intestine ◽  
Haemonchus Contortus ◽  
Alimentary Tract ◽  
Intestinal Parasites ◽  
Low Oxygen ◽  
Nematode Parasites ◽  
Partial Pressures ◽  
Consumption Rates

Nippostrongylus muris, Haemonchus contortus, Nematodirus spathiger, and N. filicollis are all capable of utilizing oxygen for respiratory purposes even when it is present at very low oxygen tensions. Thus with a partial pressure as low as 5 mm. of mercury the respiration of Nippostrongylus muris may reach 40 per cent. of its maximum rate, whereas Nematodirus spp. and H. contortus may respire at 25 and 12 per cent. of their maximum rates respectively. Further, the results indicate that in vivo the oxygen consumption rates may sometimes reach 80 per cent. of the maximum in vitro rate in the case of Nippostrongylus muris in the small intestine of the rat and 40 per cent. in the case of Nematodirus spp. in the small intestine of the sheep. Haemonchus contortus in the sheep abomasums probably respires at a relatively lower rate than either of the intestinal parasites in vivo.

scholarly journals Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Mhc I ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD down-regulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression. Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

scholarly journals Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Mhc I ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo. Methods In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion. Results We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD downregulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression. Conclusions These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia

2018 ◽  
Vol 18 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Denis V. Mishchenko ◽  
Margarita E. Neganova ◽  
Elena N. Klimanova ◽  
Tatyana E. Sashenkova ◽  
Sergey G. Klochkov ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Acute Toxicity ◽  
Histone Deacetylases ◽  
Hydroxamic Acids ◽  
Water Soluble ◽  
Male Rat ◽  
Hybrid Male ◽  
Cyclic Hydroxamic Acids

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

scholarly journals Development, Characterization and In Vivo Pharmacokinetic Assessment of Rectal Suppositories Containing Combination Antiretroviral Drugs for HIV Prevention

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1110
Author(s):  
Kunal Jhunjhunwala ◽  
Charles W. Dobard ◽  
Sunita Sharma ◽  
Natalia Makarova ◽  
Angela Holder ◽  
...  
Keyword(s):  
Hiv Prevention ◽  
Antiretroviral Drugs ◽  
Water Soluble ◽  
Fixed Dose ◽  
Receptive Anal Intercourse ◽  
On Demand ◽  
Dose Combination ◽  
Rectal Suppositories

Receptive anal intercourse (RAI) contributes significantly to HIV acquisition underscoring the need to develop HIV prevention options for populations engaging in RAI practices. We explored the feasibility of formulating rectal suppositories with potent antiviral drugs for on-demand use. A fixed-dose combination of tenofovir (TFV) and elvitegravir (EVG) (40 mg each) was co-formulated in six different suppository bases (three fat- and three water-soluble). Fat-soluble witepsol H15 and water-soluble polyethylene glycol (PEG) based suppositories demonstrated favorable in vitro release and were advanced to assess in vivo pharmacokinetics following rectal administration in macaques. In vivo drug release profiles were similar for both suppository bases. Median concentrations of TFV and EVG detected in rectal fluids at 2 h were 1- and 2-logs higher than the in vitro IC50, respectively; TFV-diphosphate levels in rectal tissues met or exceeded those associated with high efficacy against rectal simian HIV (SHIV) exposure in macaques. Leveraging on these findings, a PEG-based suppository with a lower dose combination of tenofovir alafenamide (TAF) and EVG (8 mg each) was developed and found to achieve similar rectal drug exposures in macaques. This study establishes the utility of rectal suppositories as a promising on-demand strategy for HIV PrEP and supports their clinical development.

scholarly journals Reductions of copper ion-mediated low-density lipoprotein (LDL) oxidations of trypsin inhibitors, the sweet potato root major proteins, and LDL binding capacities

2020 ◽  
Vol 61 (1) ◽  
Author(s):  
Yeh-Lin Lu ◽  
Chia-Jung Lee ◽  
Shyr-Yi Lin ◽  
Wen-Chi Hou
Keyword(s):  
Sweet Potato ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Trypsin Inhibitors ◽  
Water Soluble ◽  
Affinity Column ◽  
Low Density ◽  
Native Page

Abstract Background The root major proteins of sweet potato trypsin inhibitors (SPTIs) or named sporamin, estimated for 60 to 80% water-soluble proteins, exhibited many biological activities. The human low-density lipoprotein (LDL) showed to form in vivo complex with endogenous oxidized alpha-1-antitrypsin. Little is known concerning the interactions between SPTIs and LDL in vitro. Results The thiobarbituric-acid-reactive-substance (TBARS) assays were used to monitor 0.1 mM Cu2+-mediated low-density lipoprotein (LDL) oxidations during 24-h reactions with or without SPTIs additions. The protein stains in native PAGE gels were used to identify the bindings between native or reduced forms of SPTIs or soybean TIs and LDL, or oxidized LDL (oxLDL). It was found that the SPTIs additions showed to reduce LDL oxidations in the first 6-h and then gradually decreased the capacities of anti-LDL oxidations. The protein stains in native PAGE gels showed more intense LDL bands in the presence of SPTIs, and 0.5-h and 1-h reached the highest one. The SPTIs also bound to the oxLDL, and low pH condition (pH 2.0) might break the interactions revealed by HPLC. The LDL or oxLDL adsorbed onto self-prepared SPTIs-affinity column and some components were eluted by 0.2 M KCl (pH 2.0). The native or reduced SPTIs or soybean TIs showed different binding capacities toward LDL and oxLDL in vitro. Conclusion The SPTIs might be useful in developing functional foods as antioxidant and nutrient supplements, and the physiological roles of SPTIs-LDL and SPTIs-oxLDL complex in vivo will investigate further using animal models.

scholarly journals Activity of Indenoisoquinolines against African Trypanosomes

2008 ◽  
Vol 53 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Rahul P. Bakshi ◽  
Dongpei Sang ◽  
Andrew Morrell ◽  
Mark Cushman ◽  
Theresa A. Shapiro
Keyword(s):  
Anticancer Agents ◽  
Mammalian Cells ◽  
Sleeping Sickness ◽  
Water Soluble ◽  
African Trypanosomes ◽  
In Vivo Experiments ◽  
Topoisomerase Ib ◽  
Topoisomerase Poisons

ABSTRACT African trypanosomiasis (sleeping sickness), caused by protozoan Trypanosoma brucei species, is a debilitating disease that is lethal if untreated. Available drugs are antiquated, toxic, and compromised by emerging resistance. The indenoisoquinolines are a class of noncamptothecin topoisomerase IB poisons that are under development as anticancer agents. We tested a variety of indenoisoquinolines for their ability to kill T. brucei. Indenoisoquinolines proved trypanocidal at submicromolar concentrations in vitro. Structure-activity analysis yielded motifs that enhanced potency, including alkylamino substitutions on N-6, methoxy groups on C-2 and C-3, and a methylenedioxy bridge between C-8 and C-9. Detailed analysis of eight water-soluble indenoisoquinolines demonstrated that in trypanosomes the compounds inhibited DNA synthesis and acted as topoisomerase poisons. Testing these compounds on L1210 mouse leukemia cells revealed that all eight were more effective against trypanosomes than against mammalian cells. In preliminary in vivo experiments one compound delayed parasitemia and extended survival in mice subjected to a lethal trypanosome challenge. The indenoisoquinolines provide a promising lead for the development of drugs against sleeping sickness.

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