scholarly journals Anti-Candida Activity of Hyaluronic Acid Combined with Lactobacillus crispatus Lyophilised Supernatant: A New Antifungal Strategy

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 628
Author(s):  
Carola Parolin ◽  
Angela Abruzzo ◽  
Barbara Giordani ◽  
Josidel C. Oliver ◽  
Antonella Marangoni ◽  
...  

Vulvovaginal candidiasis (VVC) and recurrencies are common in reproductive-aged women. The emergence of Candida strains resistant to conventional antimycotic drugs prompted the search for alternative therapies. Hyaluronic acid (HA), a uniform and linear glycosaminoglycan, has been proposed as an anti-Candida agent. Vaginal lactobacilli and their derivatives, including cell free culture supernatants (CFS), represent potential strategies for the treatment of Candida infections. In the present paper, the anti-Candida potential of HA and lyophilised CFS (LCFS), obtained from the vaginal strain Lactobacillus crispatus BC5, was investigated. HA and LCFS proved to be active towards a panel of clinical Candida isolates belonging to different species in a dose dependent manner and their association maintained the antifungal activity. Notably, also Candida species generally resistant to conventional antifungals resulted sensitive. A vaginal matrix based on microcrystalline cellulose and containing effective doses of both agents was developed and characterised. This vaginal formulation showed mucoadhesive ability and almost abrogated Candida albicans growth. In conclusion, HA and LCFS from L. crispatus BC5 are thus good candidates to design a new therapeutic strategy to counteract VVC, and the proposed vaginal matrix represents a promising prototype.

1987 ◽  
Vol 166 (5) ◽  
pp. 1597-1602 ◽  
Author(s):  
K Sakai ◽  
T Hattori ◽  
M Matsuoka ◽  
N Asou ◽  
S Yamamoto ◽  
...  

A significant increase in CD25 antigen-positive cells by IL-1 was observed in cells of a patient with M7 acute myelogenous leukemia. Basal proliferation and expression of CD25 antigen by the M7 leukemic cells were inhibited by addition of anti-IL-1 beta antibody in a dose-dependent manner, but not by rabbit anti-IL-1 alpha antibody. Culture supernatants of these leukemic cells contained IL-1 activity, which was specifically inhibited by addition of anti-IL-1 beta antibody, and Northern blot analysis detected intracellular IL-1 beta mRNA. These results indicated that autocrine secretion of IL-1 beta was involved in proliferation of some myelogenous leukemic cells.


Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5106
Author(s):  
Héctor Isaac Rocha-González ◽  
María Elena Sánchez-Mendoza ◽  
Leticia Cruz-Antonio ◽  
Francisco Javier Flores-Murrieta ◽  
Xochilt Itzel Cornelio-Huerta ◽  
...  

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the main types of drugs used to treat pain, they have several adverse effects, and such effects can be reduced by combining two analgesic drugs. The aim of this study was to evaluate the nociceptive activity of methyleugenol combined with either diclofenac or ketorolac, and determine certain parameters of pharmacokinetics. For the isobolographic analysis, the experimental effective dose 30 (ED30) was calculated for the drugs applied individually. With these effective doses, the peak plasma concentration (Cmax) was found and the other parameters of pharmacokinetics were established. Methyleugenol plus diclofenac and methyleugenol plus ketorolac decreased licking behavior in a dose-dependent manner in phase II, with an efficacy of 32.9 ± 9.3 and 39.8 ± 9.6%, respectively. According to the isobolographic analysis, the experimental and theoretical ED30 values were similar for methyleugenol plus diclofenac, suggesting an additive effect, but significantly different for methyleugenol plus ketorolac (3.6 ± 0.5 vs. 7.7 ± 0.6 mg/kg, respectively), indicating a probable synergistic interaction. Regarding pharmacokinetics, the only parameter showing a significant difference was Cmax for the methyleugenol plus diclofenac combination. Even with this difference, the combinations studied may be advantageous for treating inflammatory pain, especially for the combination methyleugenol plus ketorolac.


Microbiology ◽  
2009 ◽  
Vol 155 (4) ◽  
pp. 1282-1293 ◽  
Author(s):  
Keiko Sato ◽  
Nobuo Kido ◽  
Yukitaka Murakami ◽  
Charles I. Hoover ◽  
Koji Nakayama ◽  
...  

The periodontopathic bacterium Porphyromonas gingivalis forms pigmented colonies when incubated on blood agar plates as a result of accumulation of μ-oxo haem dimer on the cell surface. Gingipain–adhesin complexes are responsible for production of μ-oxo haem dimer from haemoglobin. Non-pigmented mutants (Tn6-5, Tn7-1, Tn7-3 and Tn10-4) were isolated from P. gingivalis by Tn4351 transposon mutagenesis [Hoover & Yoshimura (1994), FEMS Microbiol Lett 124, 43–48]. In this study, we found that the Tn6-5, Tn7-1 and Tn7-3 mutants carried Tn4351 DNA in a gene homologous to the ugdA gene encoding UDP-glucose 6-dehydrogenase, a gene encoding a putative group 1 family glycosyltransferase and a gene homologous to the rfa gene encoding ADP heptose-LPS heptosyltransferase, respectively. The Tn10-4 mutant carried Tn4351 DNA at the same position as that for Tn7-1. Gingipain activities associated with cells of the Tn7-3 mutant (rfa) were very weak, whereas gingipain activities were detected in the culture supernatants. Immunoblot and mass spectrometry analyses also revealed that gingipains, including their precursor forms, were present in the culture supernatants. A lipopolysaccharide (LPS) fraction of the rfa deletion mutant did not show the ladder pattern that was usually seen for the LPS of the wild-type P. gingivalis. A recombinant chimera gingipain was able to bind to an LPS fraction of the wild-type P. gingivalis in a dose-dependent manner. These results suggest that the rfa gene product is associated with biosynthesis of LPS and/or cell-surface polysaccharides that can function as an anchorage for gingipain–adhesin complexes.


Author(s):  
Raina Jain ◽  
Ashish Jain

Background: To evaluate the anticonvulsant activity of Nimodipine alone and in combination with Phenytoin, in MES induced seizures.Methods: The study was conducted in mice and MES seizure was induced by Techno electroconvulsometer. In first part of study, animals were treated with Nimodipine (20mg/kg i.p. and 40mg/kg i.p.) and Phenytoin (0.5 mg/100g i.p. and 1.0mg/100g i.p.), MES was induced and durations of various phases were noted. Duration of Tonic hind limb extension (THLE) was taken as index for antiepileptic activity. In second part, the animals were treated with combination of sub effective doses of Nimodipine (20mg/kg i.p.) and Phenytoin (0.5mg/100g i.p.), MES was induced and durations of various phases were noted.Results: Nimodipine produced significant antiepileptic activity, in dose dependent manner. Phenytoin produced significant antiepileptic effect in dose of 1.0mg/100g but failed to produce any such effect in dose of 0.5mg/100g, when administered alone. But when sub effective doses.Of Nimodipine and Phenytoin were combined, a synergistic effect was seen.Conclusions: Nimodipine possess significant antiepileptic activity, alone, as well as it potentiates the antiepileptic effect of Phenytoin, suggesting the novel application of already proven safe and efficacious calcium channel blockers.


2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Mi-Seong Kim ◽  
Ha-Rim Kim ◽  
Hong-Seob So ◽  
Young-Rae Lee ◽  
Hyoung-Chul Moon ◽  
...  

Introduction. Crotonis fructus (CF) is the mature fruit ofCroton tigliumL. and has been used for the treatment of gastrointestinal disturbance in Asia. It is well known that the main component of CF is croton oil (CO). The present study is to investigate the effects of CF extracts (CFE) and CO on lipolysis in OP9 adipocytes.Methods. Glycerol release to the culture supernatants was used as a marker of adipocyte lipolysis.Results. Treatment with various concentrations of CFE and CO stimulates glycerol release in a dose-dependent manner. The increase in glycerol release by CFE is more potent than isoproterenol, which is aβ-adrenergic agonist as a positive control in our system. The increased lipolysis by CFE and CO was accompanied by an increase of phosphorylated hormone sensitive lipase (pHSL) but not nonphosphorylated HSL protein and mRNA. Pretreatment with H89, which is a protein kinase A inhibitor, significantly abolished the CFE- and CO-induced glycerol release in OP9 adipocytes. These results suggest that CFE and CO may be a candidate for the development of a lipolysis-stimulating agent in adipocytes.


Author(s):  
Burak Derkus

AbstractAccomplishing a reliable lineage-specific differentiation of stem cells is vital in tissue engineering applications, however, this need remained unmet. Extracellular nanovesicles (particularly exosomes) have previously been shown to have this potential owing to their rich biochemical content including proteins, nucleic acids and metabolites. In this work, the potential of human cardiomyocytes-derived exosomes to induce in vitro cardiac gene expressions in human mesenchymal stem cells (hMSCs) was evaluated. Cardiac exosomes (CExo) were integrated with hyaluronic acid (HA) hydrogel, which was functionalized with tyramine (HA-Tyr) to enable the development of 3D (three dimensional), robust and bioactive hybrid cell culture construct through oxidative coupling. In HA-Tyr/CExo 3D hybrid hydrogels, hMSCs exhibited good viability and proliferation behaviours. Real time quantitative polymerase chain reaction (RT-qPCR) results demonstrated that cells incubated within HA-Tyr/CExo expressed early cardiac progenitor cell markers (GATA4, Nkx2.5 and Tbx5), but not cTnT, which is expressed in the late stages of cardiac differentiation and development. The expressions of cardiac genes were remarkably increased with increasing CExo concentration, signifying a dose-dependent induction of hMSCs. This report, to some extent, explains the potential of tissue-specific exosomes to induce lineage-specific differentiation. However, the strategy requires further mechanistic explanations so that it can be utilized in translational medicine.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Colin E Evans ◽  
Xianming Zhang ◽  
Narsa Machireddy ◽  
You-yang Zhao

Introduction: Lung thrombosis (LT) and endothelial cell (EC) death are positively associated with mortality in sepsis-induced acute lung injury (ALI) patients, but anti-coagulants have failed in clinical trials of sepsis. Hypothesis: We hypothesized that different levels of LT mediate ALI by regulating lung EC viability. Methods: To assess the impact of different levels of LT on ALI, we used murine models of LT and ALI. To explore how LT level might alter lung EC viability and ALI, we assessed survival gene expression by RNA sequencing. To identify the mechanism(s) responsible for changes in ALI after varying levels of LT, we assessed lung EC viability and ALI in mice with cell-specific knockout of different survival genes. Results: In platelet-depleted mice, LT was reduced while ALI was increased. Intra-venous microbeads were then administered to induce LT in a dose-dependent manner, showing that restoration of LT to the level found in platelet-replete mice protected against thrombocytopenia-induced ALI. We next showed in wild type mice, that while excessive increases in LT worsened ALI, induction of a mild level of LT conversely protected against ALI. The opposing impact of diminished or excessive versus mild LT on ALI was associated with changes in lung EC apoptosis. Subsequent studies showed a panel of candidate survival factors were differentially expressed in the lungs of ALI mice with or without mild or excessive LT. Mechanistically, we found that the protective impact of mild LT on ALI is dependent upon hypoxia-inducible factor (HIF) 1α in Tie2-expressing cells. Remarkably, the same mild level of LT retained its protective impact in platelet-depleted and platelet-replete mice even when induced up to 8 hours after sepsis. Conclusions: ALI is enhanced by diminished or excessive LT but suppressed by mild LT through HIF1α. The control of LT represents a therapeutic strategy for the induction of a pro-survival response that protects against inflammatory lung injury.


Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 698-704 ◽  
Author(s):  
C Gachet ◽  
A Astier ◽  
H de la Salle ◽  
C de la Salle ◽  
WH Fridman ◽  
...  

Thrombin-activated human platelets and megakaryocyte cell lines release soluble Fc gamma RII (Fc gamma RIIa2) containing the extracellular and intracellular regions of Fc gamma RIIa1, but lacking the transmembrane domain. Use of polyclonal antibodies directed either against the entire intracytoplasmic tail, or against a peptide located near the C-terminal part of the intracellular region of Fc gamma RIIa2, showed the presence of both a complete form of Fc gamma RIIa2 and a C-terminal truncated form in supernatants of platelets after release of their alpha granule contents and in culture supernatants of megakaryocyte cell lines. Furthermore, recombinant Fc gamma RIIa2 inhibited in a dose-dependent manner Fc-dependent anti-CD9 antibody-induced platelet aggregation. Thus, release of Fc gamma RIIa2 by activated platelets could play an important role in the regulation of platelet activation by immune complexes.


Author(s):  
Jain Raina ◽  
Jain Ashish

Objective: To evaluate the anticonvulsant activity of Nimodipine alone and in combination with Phenytoin, in MES induced seizures.Methods: The study was conducted in mice and MES seizure was induced by Techno electro-convulsometer. In the first part of the study, animals were treated with Nimodipine (20 mg/kg i. p. and 40 mg/kg i. p.) and Phenytoin (0.5 mg/100g i. p. and 1.0 mg/100g i. p.), MES was induced and durations of various phases were noted. Duration of Tonic hindlimb extension (THLE) was taken as an index for antiepileptic activity. In the second part, the animals were treated with a combination of sub effective doses of Nimodipine (20 mg/kg i. p.) and Phenytoin (0.5 mg/100g i. p.), MES was induced and durations of various phases were noted.Results: Nimodipine produced significant antiepileptic activity, in a dose-dependent manner. Phenytoin produced a significant antiepileptic effect in dose of 1.0 mg/100g, but failed to produce any such effect in a dose of 0.5 mg/100g, when administered alone. But when sub-effective doses. Of Nimodipine and Phenytoin were combined, a synergistic effect was seen.Conclusion: Nimodipine posses significant antiepileptic activity, alone, as well as it potentiates the antiepileptic effect of Phenytoin, suggesting the novel application of already proven safe and efficacious calcium channel blockers.


1990 ◽  
Vol 45 (7-8) ◽  
pp. 873-880 ◽  
Author(s):  
Eimei Sato ◽  
Hajime Miyamoto ◽  
Samuel S. Koide

Abstract Glycosaminoglycans prepared from extracts of non-luleal mouse ovaries (JCL-ICR strain) were assayed for neovascularization by implanting Elvax films, impregnated with test samples, on the lateral wall of the sheath of m. rectus abdominis in adult mice of the same strain. Neovascularization occurred in a dose-dependent manner. When purified by chromatography on Dowcx 1-x 2 and DEAE Sephadex columns, fractions eluted with 0.5 M NaCl showed strong ncovascularizing activity. On further purification by high performance liquid chromatography using TSK gel DEAE 2SW column, the fraction with a retention time nearly coincident with that of hyaluronic acid possessed high ncovascularizing activity. The activity of this fraction was markedly reduced when treated with streptococcal hyaluronidase. The present results suggest that glycosaminoglycans, especially a hyaluronic acid-like substance, are involved in ovarian neovascularization.


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