scholarly journals Protective effect of cytosine-phosphate-guanosine oligodeoxynucleotide against experimental mastitis induced by Cryptococcus neoformans infection in goats

2017 ◽  
Vol 40 (2) ◽  
pp. 113-123
Author(s):  
Nidhal R. Mahdi

     The present study investigated the effect of synthetic non-methylated oligonucleotides containing Cytosine-phosphate-guanosine dinucleotides (Cytosine-phosphate-guanosine oligodeoxynucleotide) on caprine mastitis with Heat Killed Cryptococcus neoformans Ag. 20 healthy local breed does were used with weight ranging of 25-30 Kg and free of mastitis by examination via California Mastitis Test and Somatic Cell Count. The does were allotted into four equal groups, the first group (G1) was treated intramammary with 100μg/kg of Cytosine-phosphate-guanosine oligodeoxy nucleotide on fifth day postpartum in the right mammary gland while the left mammary gland served as control and were infused with sterile phosphate buffered saline. On day 8 postpartum repeat dosages of Cytosine-phosphate-guanosine oligodeoxynucleotide and phosphate buffered saline were infused respectively. On day 9 pp the right mammary gland was infused with 2ml of 2x108 cell/ml of Heat Killed Cryptococcus neoformans Ag. The second group (G2) was infused at day 9 postpartum with 2ml of 2x108 cell/ml of Heat Killed Cryptococcus neoformans Ag in the right mammary gland only. The third group (G3) was left until the challenge test done after one week of immunization in the G1 and G2, by inoculation of 2ml of 5x106 viable C. neoformans in the right mammary gland. The fourth group (G4) was kept as a control receiving 2ml of sterile PBS. Blood samples were collected at 0, 5, 10, 20, 30 and 40 days of the study, to determine the antibody titer by passive haemagglutination assay, while the cell mediated immunity was evaluated by detecting the goat Interferon Gamma by ELISA test and Phagocytic index. Also the cell mediated immunity was determined by delayed type hypersensitivity test after 21 days of immunization. The results showed a significant variation (P≤0.05) between vaccinated groups (G1 and G2) and the control. However, there was a significant increase (P≤0.05) of skin thickness shown after 48 hrs in the G1compared to G2. High level of Interferon Gamma concentration was noticed in the G1 as compared with other groups. Moreover, cell mediated immunity developed effectively in the G1 which was noted by a significant increase (P≤0.05) of phagocytic activity of polymorphonuclear cells. The high level of antibody titer was observed in the G1 as compared with other groups. In conclusion: These results suggest that vaccination with Cytosine-phosphate-guanosine oligodeoxynucleotide plus Heat Killed Cryptococcus neoformans Ag intramammary lead to a good protection of caprine mammary glands against C. neoformans mastitis.

Author(s):  
Annapurna Akula ◽  
Chandi Vishala ◽  
Gummalla Pitchaiah

Objective: This study prepared, evaluated immunomodulatory activity of nutraceutical formulation and studied the effect of self-mortification and cow urine distillate fortification methods on the immunomodulatory potential of nutraceutical formulation.Methods: Three types of nutraceutical formulations i.e. Nutraceutical formulation (NF), self fortitfied nutraceutical formulation (SFNF) and self fortitfied nutraceutical formulation fortified with cow urine distillate (SFNECUD) were prepared using fine powders of amla, apple, garlic, onion, wheat grass, papaya, turmeric and cow urine distillate by different methods. The immunomodulatory activity of nutraceutical formulations at a dose of 500 mg/kg was assessed by various immune function parameters like cell-mediated immunity (neutrophil adhesion, delayed type hypersensitivity (DTH) response and cyclophosphamide-induced neutropenia), humoral immunity (serum immunoglobulins level and haemoagglutination antibody titer), and phagocytic activity (carbon clearance and polymorphonuclear (PMN) cell activity).Results: Oral administration of NF, SFNF and SFNFCUD showed significant (p<0.01) increase in adhesion of neutrophils, potentiation of the DTH reaction and attenuation of cyclophosphamide-induced neutropenia. A significant increase in serum immunoglobulin levels and production of circulating antibody titer in response to sheep red blood cells (SRBCs) was also observed. In addition, an increase in the phagocytic index in carbon clearance assay and an increase in the phagocytic activity of PMN cells was observed.Conclusion: From the above results, it can be concluded that all three types of formulations showed significant immunostimulant activity. SFNF and SFNFCUD showed better immunomodulatory activity than NF suggesting the potentiation of immunomodulatory potential of NF activity by fortification methods.


2002 ◽  
Vol 70 (2) ◽  
pp. 591-600 ◽  
Author(s):  
Kasie L. Nichols ◽  
Sean K. Bauman ◽  
Fredda B. Schafer ◽  
Juneann W. Murphy

ABSTRACT Cell-mediated immunity is the major protective mechanism against Cryptococcus neoformans. Delayed swelling reactions, i.e., delayed-type hypersensitivity (DTH), in response to an intradermal injection of specific antigen are used as a means of detecting a cell-mediated immune (CMI) response to the antigen. We have found previously that the presence of an anticryptococcal DTH response in mice is not always indicative of protection against a cryptococcal infection. Using one immunogen that induces a protective anticryptococcal CMI response and one that induces a nonprotective response, we have shown that mice immunized with the protective immunogen undergo a classical DTH response characterized by mononuclear cell and neutrophil infiltrates and the presence of gamma interferon and NO. In contrast, immunization with the nonprotective immunogen results in an influx of primarily neutrophils and production of tumor necrosis factor alpha (TNF-α) at the DTH reaction site. Even when the anticryptococcal DTH response was augmented by blocking the down-regulator, CTLA-4 (CD152), on T cells in the mice given the nonprotective immunogen, the main leukocyte population infiltrating the DTH reaction site is the neutrophil. Although TNF-α is increased at the DTH reaction site in mice immunized with the nonprotective immunogen, it is unlikely that TNF-α activates the neutrophils, because the density of TNF receptors on the neutrophils is reduced below control levels. Uncoupling of DTH reactivity and protection has been demonstrated in other infectious-disease models; however, the mechanisms differ from our model. These findings stress the importance of defining the cascade of events occurring in response to various immunogens and establishing the relationships between protection and DTH reactions.


2021 ◽  
pp. 464-473
Author(s):  
Dicki Bakhtiar Purkon

Immunostimulants are compounds that can stimulate an immune response by increasing the activity of non-specific and specific components of the immune system (humoral and cellular) against certain infections and diseases. The liverwort plant species Marchantia paleacea Bertol. has long been used as a source of nutrition and empirical medicine. However, scientifically there is still not much research data on immunomodulators in these plants. This study aims to determine the activity of immunomodulators in the ethanol extract of the herb Marchantia paleacea Bertol. in male mice of BALB/c strain. Bioactive compounds from this plant were extracted by maceration method using 96% ethanol. Extract characterization and phytochemical screening were determined according to WHO guidelines and standard procedures from previous studies. The immunomodulatory activity of the extract was tested by carbon clearance method and lymphoid organ index (non-specific responses), primary and secondary antibody titer tests (humoral specific responses), IL-2 cytokine levels and IFN-ɣ from serum secondary antibodies and delayed-type hypersensitivity reaction/DTH (cellular specific response). The results of qualitative phytochemical screening contained flavonoid compounds, saponins, phenolics, tannins and steroids/triterpenoids. The results of the non-specific immune response immunomodulator test showed that the dose of 52 mg/kg bw had the largest phagocytic index of 1.52 which included strong immunostimulation (K > 1.5) and the organ spleen index of 0.55 ± 0.11 which increased significantly compared to the control (p<0.05). The data on the acquisition of specific immune responses in the primary and secondary antibody titer test in the three test extracts resulted in increased titer levels compared to the control and at a dose of 52 mg/kg bw could significantly increase the levels of IL-2 cytokines in the control group (p<0,05). Meanwhile, in the DTH test, doses of 13 and 26 mg/kg bw could significantly increase the thickness of the soles of mice compared to controls (p<0.05).


Author(s):  
VANITA G KANASE ◽  
SHRUTI SHETTIGAR

Objective: The present study was intended to evaluate the in vivo immunomodulatory activity of aqueous and ethanolic extract of dried fruits of Capparis moonii Wight. Methods: The effect of both the extracts was evaluated by carbon clearance assay in mice, and they showed a significant increase in the phagocytic index at 50, 100, and 200 mg/kg dose. The effect of the extracts on delayed-type hypersensitivity (DTH) and antibody titer assay was evaluated in ovalbumin immunized mice. Results: Both extracts showed a significant effect on DTH response and stimulation of antibody titer at 200 mg/kg dose. The effects of the extracts in cyclophosphamide-induced myelosuppression mice were also statistically significant. Conclusion: The studies demonstrated specific and non-specific immunostimulating properties of both the ethanol and aqueous extract of C. moonii fruits in various in vivo experimental methods suggesting its therapeutic usefulness in immunocompromised conditions.


Author(s):  
Priyanka Shrestha ◽  
Mukund Handral

<p><strong>Objective: </strong><em>Nephelium</em> <em>lappaceum</em> Linn (Sapindaceae), also known as Rambutan is a tropical fruit native to Malaysia. The rind of Rambutan, which is normally discarded, has been used in the present research work to explore the immunomodulatory activity of ethanolic extract and also its protective effect against cyclophosphamide (CP) induced immunosuppression.</p><p><strong>Methods: </strong>The assessment of immunomodulatory activity was carried by testing the humoral (Haemagglutination antibody titre (HA) model), cell-mediated immunity (delayed type hypersensitivity reaction model), haematological parameters, carbon clearance assay (phagocytic index), organ index (spleen and thymus) and histopathological study of mice thymus.</p><p><strong>Results: </strong>Administration of the ethanolic extract significantly increased the antibody titre and DTH response in response to sheep red blood cells when compared to normal control and CP control group. There was a prominent increase in the WBC count, spleen index, thymus index and the phagocytic index in immune suppressed group treated with ethanolic extract of <em>Nephelium lappaceum</em> rind compared to the immune suppressed control group.</p><p><strong>Conclusion: </strong>The result suggests that the ethanolic extract has the potential to modulate the immune system as well has a protective effect against CP-induced immune suppression.</p>


Author(s):  
Sanjiv Kumar Biradar ◽  
Chandra Kishore Tyagi

Tinospora cordifolia is a plant well known for its medicinal value in Indian ayurveda and Indian traditional medicine system. However, to prove its efficiency for the clinical utilization, more experimental data will be beneficial. In the present investigation, evaluated the immunomodulatory activity of the alcoholic extracts of Tinospora cordifolia stem on various in-vivo experimental models such as neutrophil adhesion test, phagocytic index by carbon clearance test, Hemagglutinating antibody (HA) titre and delayed type hypersensitivity (DTH) responses. The evaluation of immunomodulatory potential by oral administration of alcoholic stem extracts (50, 100, 200 and 300mg/kg b.w, p.o) evoked a significant increase in percent neutrophil adhesion to nylon fibers as well as a dose dependent increased in antibody titre values, and potentiated delayed type hypersensitivity reaction induced by sheep red blood cells and significant response towards phagocytosis in carbon clearance assay (*p<0.05, *p<0.01, ***p<0.001). This may be due to concentrations of active phytochemicals present in particular plant extract. Hence, it was concluded that the plant extracts increased humoral as well as cell mediated immunity.


2019 ◽  
Vol 65 (1) ◽  
pp. 27-41
Author(s):  
Yelena Artamonova

Lung cancer is the leading cause of mortality from malignant tumors all over the world. Since most patients at the time of diagnosis already have stage III-IV of the disease, the search for new effective treatment strategies for advanced NSCLC is the most important problem of modern oncology. The results of the study of the anti-PD1 monoclonal antibody pembrolizumab were a real breakthrough in the treatment of NSCLC. In the KEYN0TE-001 study, the expression of PD-L1 on tumor cells was validated as a predictive biomarker of the drug's efficiency. Pembrolizumab demonstrated the possibility of achieving long-term objective responses, and a 4-year 0S with all histological types in the subgroup of pre-treated patients with PD-L1 expression> 50% was 24.8% and 15.6% in the PD-L1> 1% group. In a phase 2/3 randomized study KEYN0TE-10 in the 2nd line treatment of NSCLC with PD-L1 expression > 1% pembrolizumab significantly increased life expectancy compared to docetaxel and confirmed the possibility of longterm duration of objective responses, even after cessation of treatment. Then the focus of research shifted to the 1st line of treatment. About 30% of patients with NSCLC have a high level of PD-L1 expression on tumor cells and demonstrate the most impressive response to pembrolizumab therapy. A randomized phase 3 study KEYN0TE-024 compared the effectiveness of pembrolizumab monotherapy with a standard platinum combination in patients with advanced NSCLC with a high level of PD-L1 expression without EGFR mutations or ALK translocation. Compared with the platinum doublet the administration of pembrolizumab significantly increased all estimated parameters, including the median of progression-free survival (mPFS was 10.3 months versus 6 months; HR = 0.50; 95% CI 0.37-0.68, p < 0.001), the objective response rate (ORR 44.8% versus 27.8%), duration of response (in the pembrolizumab arm the median was not reached, in the chemotherapy (CT) group - 6.3 months). Despite the approved crossover, the use of pembrolizumab in the 1st line of treatment more than doubled the life expectancy of NSCLC patients with high PD-L1 expression as compared to CT: the median overall survival (OS) was 30.0 months versus 14.2 months (HR = 0.63, p = 0.002), 1-year OS 70.3% versus 54.8%; 2-year OS - 51.5% versus 34.5%. The remaining population to study were untreated patients with any level of PD-L1 expression. A randomized phase 3 study KEYNOTE-189 evaluated the effectiveness of adding pembrolizumab to the platinum combination in the 1st line treatment of non-squamous NSCLC without EGFR and ALK mutations with any PD-L1 expression. The addition of pembrolizumab to the standard 1st line CT significantly increased all estimated efficacy indicators including OS, PFS and ORR. After a median follow-up of 10.5 months the median OS in the pembrolizumab combination group was not reached and in CT group was 11.3 months. The estimated 12-months survival was 69.2% and 49.4% respectively (HR = 0.49; 95% CI 0.38-0,64; p <0.001). The median PFS was 8.8 months versus 4.9 months, alive 1 year without progression 34.1% and 17.3% of patients respectively (HR = 0.52; p <0.001). The ORR in the group with pembrolizumab reached 47.6% versus 18.9% in CT group, moreover the tumor regressions were much longer. Finally a randomized 3-phase study KEYN0TE-407 evaluated the effectiveness of adding pembrolizumab to 1st-line CT of NSCLC with squamous histology with any PD-L1 expression. As the first analysis showed, the addition of permboli-zumab significantly increased OS of patients with squamous NSCLC, median OS 15.9 months versus 11.3 months in the groups of pembrolizumab + CT and placebo + CT respectively (HR = 0.64; 95% CI 0,49-0.95; p = 0.0006), median PFS 6.4 months and 4.8 months respectively (HR = 0.56; 95% CI 0.450.70; p <0, 0001) and OrR 57.9% versus 38.4%, the median response duration 7.7 months versus 4.8 months. Thus, the convincing advantages of using pembrolizumab in 1st line therapy were demonstrated in 3 randomized phase 3 studies: in monotherapy of NSCLC of any histological subtype with high PD-L1 expression, and in combination with CT in squamous and non-squamous hystologies regardless of the level of PD-L1 expression.


Author(s):  
Yun-Hee Kim ◽  
Sung-Uk Choi ◽  
Jung-Min Youn ◽  
Seung-Ha Cha ◽  
Hyeon-Ju Shin ◽  
...  

BACKGROUND: The prevention of rheologic alterations in erythrocytes may be important for reducing sepsis-associated morbidity and mortality. Remote ischemic preconditioning (RIPC) has been shown to prevent tissue damage caused by severe ischemia and mortality resulting from sepsis. However, the effect of RIPC on erythrocytes in sepsis is yet to be determined. OBJECTIVE: To investigate the effect of RIPC on rheologic alterations in erythrocytes in sepsis. METHODS: Thirty male Sprague-Dawley rats were used in this study. An endotoxin-induced sepsis model was established by intraperitoneally injecting 20 mg/kg LPS (LPS group). RIPC was induced in the right hind limb using a tourniquet, with three 10-minute of ischemia and 10 min of reperfusion cycles immediately before the injection of LPS (RIPC/LPS group) or phosphate-buffered saline (RIPC group). The aggregation index (AI), time to half-maximal aggregation (T1/2), and maximal elongation index (EImax) of the erythrocytes were measured 8 h after injection. RESULTS: The AI, T1/2, and EImax values in the LPS and RIPC/LPS groups differed significantly from those in the RIPC group, but there were no differences between the values in the LPS and RIPC/LPS groups. CONCLUSIONS: RIPC did not prevent rheologic alterations in erythrocytes in the rat model of LPS-induced endotoxemia.


Author(s):  
Aida Mekhoukhe ◽  
Nacer Mohellebi ◽  
Tayeb Mohellebi ◽  
Leila Deflaoui-Abdelfettah ◽  
Sonia Medouni-Adrar ◽  
...  

OBJECTIVE: the present work proposed to extract Locust Bean Gum (LBG) from Algerian carob fruits, evaluate physicochemical and rheological properties (solubility). It aimed also to develop different formulations of strawberry jams with a mixture of LBG and pectin in order to obtain a product with a high sensory acceptance. METHODS: the physicochemical characteristics of LBG were assessed. The impact of temperature on solubility was also studied. The physical and the sensory profile and acceptance of five Jams were evaluated. RESULTS: composition results revealed that LBG presented a high level of carbohydrate but low concentrations of fat and ash. The LBG was partially cold-water-soluble (∼62% at 25°C) and needed heating to reach a higher solubility value (∼89% at 80 °C). Overall, the sensorial acceptances decreased in jams J3 which was formulated with 100% pectin and commercial one (J5). The external preference map explained that most consumers were located to the right side of the map providing evidence that most samples appreciated were J4 and J2 (rate of 80–100%). CONCLUSION: In this investigation, the LBG was used successfully in the strawberry jam’s formulation.


Metals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1100
Author(s):  
Alexandre M. Emelyanenko ◽  
Valery V. Kaminsky ◽  
Ivan S. Pytskii ◽  
Kirill A. Emelyanenko ◽  
Alexander G. Domantovsky ◽  
...  

The interest in magnesium-based materials is promoted by their biocompatibility, their bioresorbability, and their recently discovered antibacterial potential. Until now, the widespread use of magnesium alloys in different corrosive environments was inhibited by their weakly controllable degradation rate and poorly understood microbiologically induced corrosion behavior. To better understand the degradation and usability of magnesium-based alloys, in this study we have fabricated superhydrophobic coatings on a magnesium-based alloy, and analyzed the behavior of this alloy in bacterial dispersions of Pseudomonas aeruginosa and Klebsiella pneumoniae cells in phosphate-buffered saline. It was shown that the immersion of such coatings in bacterial dispersions causes notable changes in the morphology of the samples, dependent on the bacterial dispersion composition and the type of bacterial strain. The interaction of the superhydrophobic coatings with the bacterial dispersion caused the formation of biofilms and sodium polyphosphate films, which provided enhanced barrier properties in magnesium dissolution and hence in dispersion medium alkalization, eventually leading to the inhibition of magnesium substrate degradation. The electrochemical data obtained for superhydrophobic samples in continuous contact with corrosive bacterial dispersions for 48 h indicated a high level of anticorrosion protection.


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