Testing Antifungal Vaccines in an Animal Model of Invasive Candidiasis and in Human Mucosal Candidiasis

Invasive candidiasis (IC) represents the leading fungal infection of humans causing life-threatening disease in immunosuppressed and neutropenic individuals including also the intensive care unit patients. Despite progress in recent years in drugs development for the treatment of IC, morbidity and mortality rates still remain very high. Historically, cell-mediated immunity and innate immunity are considered to be the most important lines of defense against candidiasis. Nevertheless recent evidence demonstrates that antibodies with defined specificities could act with different degrees showing protection against systemic and mucosal candidiasis. Mycograb is a human recombinant monoclonal antibody against heat shock protein 90 (Hsp90) that was revealed to have synergy when combined with fluconazole, caspofungin, and amphotericin B against a broad spectrum ofCandidaspecies. Furthermore, recent studies have established an important role for Hsp90 in mediatingCandidaresistance to echinocandins, giving to this antibody molecule even more attractive biological properties. In response to the failure of marketing authorization by the CHMP (Committee for Medicinal Products for Human Use) a new formulation of Mycograb, named Mycograb C28Y variant, with an amino acid substitution was developed in recent years. First data on Mycograb C28Y variant indicate that this monoclonal antibody lacked efficacy in a murine candidiasis model.

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A Review on Candidiasis resistance current drug development process in its prevention and treatment

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i1.1938 ◽

2020 ◽

Vol 11 (1) ◽

pp. 1073-1079

Author(s):

Guruprasad B M ◽

Famna Roohi N K ◽

Gowda D V

Keyword(s):

Fungal Infection ◽

Amphotericin B ◽

Invasive Candidiasis ◽

Culture Method ◽

Vulvovaginal Candidiasis ◽

The Other ◽

Examination Methods ◽

Cutaneous Candidiasis ◽

Mucosal Candidiasis ◽

Novel Drug

A fungal infection caused by Candida albicans leads to illness and death worldwide. This review mainly focused upon Vulvovaginal Candidiasis that is a common fungal infection seen in women, especially during pregnancy; Candida species cause diseases, particularly in immunocompromised patients. This type of infection occurred during the nonsterile environment. The different types of candidiasis mentioned in this review are Mucosal Candidiasis, Oropharyngeal Candidiasis, Vulvovaginal Candidiasis, Cutaneous Candidiasis, Invasive Candidiasis, Disseminated candidiasis, and Candidemia. New approaches like vaccination, antibodies, cytokine therapy, amphotericin-B loaded nanofiber, mucoadhesive are required to improve the result of the patients suffering from infections. New insights into the mechanism of anticandidal host response have contributed to the design of novel immunotherapy. The systemic and topical treatment is carried. The novel drug therapy is given in order to avoid the resistivity developed by fungus. Diagnosis is made by different techniques like direct examination and Culture Method. The other examination methods used are Pathogen-related tests, mannan tests, nucleic acid-based assays. Amphotericin–B loaded nanofibers and liposomes are developed and even certain plant extracts are using as an antifungal drug which is safer to use the future trends used for the study are Echinocandins, the latest class of drug used for the antifungal and drug act as a fungicidal that has low drug-drug interaction which makes first-line treatment for invasive candidiasis particularly. The different class of drugs has been used for the treatment are discussed with Azoles that are used in the treatment with a combination of the other class drugs.

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Pharmacodynamic Optimization for Treatment of Invasive Candida auris Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00791-17 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 36

Author(s):

Alexander J. Lepak ◽

Miao Zhao ◽

Elizabeth L. Berkow ◽

Shawn R. Lockhart ◽

David R. Andes

Keyword(s):

Animal Model ◽

Steady State ◽

Invasive Candidiasis ◽

Maximum Concentration ◽

Multidrug Resistant ◽

Total Drug ◽

Candida Auris ◽

Time Curve ◽

Content Type ◽

Concentration Time

ABSTRACT Candida auris is an emerging multidrug-resistant threat. The pharmacodynamics of three antifungal classes against nine C. auris strains was explored using a murine invasive candidiasis model. The total drug median pharmacodynamic (PD) target associated with net stasis was a fluconazole AUC/MIC (the area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 26, an amphotericin B C max/MIC (maximum concentration of drug in serum divided by the MIC) of 0.9, and a micafungin AUC/MIC of 54. The micafungin PD targets for C. auris were ≥20-fold lower than those of other Candida species in this animal model. Clinically relevant micafungin exposures produced the most killing among the three classes.

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Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077086 ◽

1983 ◽

Vol 41 ◽

pp. 702-703

Author(s):

D. J. McComb ◽

J. Beri ◽

F. Zak ◽

K. Kovacs

Keyword(s):

Electron Microscopy ◽

Animal Model ◽

Epoxy Resin ◽

Immunoelectron Microscopy ◽

Tumor Type ◽

Gonadal Function ◽

Sprague Dawley ◽

Male And Female ◽

Reticulin Fibers ◽

Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

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Electron Microscopic Detection and Characterization of Nonhuman Primate Enteric Viruses

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100054145 ◽

1982 ◽

Vol 40 ◽

pp. 306-307

Author(s):

G. C. Smith ◽

R. L. Heberling ◽

S. S. Kalter

Keyword(s):

Electron Microscopy ◽

Animal Model ◽

Nonhuman Primate ◽

Clinical Condition ◽

Intestinal Tract ◽

Enteric Viruses ◽

Electron Microscopic ◽

Microscopic Detection

A number of viral agents are recognized as and suspected of causing the clinical condition “gastroenteritis.” In our attempts to establish an animal model for studies of this entity, we have been examining the nonhuman primate to ascertain what viruses may be found in the intestinal tract of “normal” animals as well as animals with diarrhea. Several virus types including coronavirus, adenovirus, herpesvirus, and picornavirus (Table I) were detected in our colony; however, rotavirus, astrovirus, and calicivirus have not yet been observed. Fecal specimens were prepared for electron microscopy by procedures reported previously.

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Neurofilaments and Paired Helical Filaments

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120357 ◽

1985 ◽

Vol 43 ◽

pp. 740-743

Author(s):

J. Metuzals

Keyword(s):

Animal Model ◽

Posttranslational Modifications ◽

Posttranslational Modification ◽

Giant Axon ◽

Paired Helical Filaments ◽

Squid Giant Axon ◽

In Vitro Experiments ◽

Thin Sections ◽

Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

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Membrane-associated microtubular areays induced in proximal myelinated processes of dorsal root ganglia by large doses of vitamin B6

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100143468 ◽

1986 ◽

Vol 44 ◽

pp. 368-369

Author(s):

V.J. Montpetit ◽

S. Dancea ◽

L. Tryphonas ◽

D.F. Clapin

Keyword(s):

Animal Model ◽

Endoplasmic Reticulum ◽

Dorsal Root Ganglia ◽

Rough Endoplasmic Reticulum ◽

Dorsal Root ◽

Vitamin B6 ◽

Morphological Changes ◽

Model System ◽

Sensory Nerves ◽

Peripheral Sensory

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.

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Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128493 ◽

1987 ◽

Vol 45 ◽

pp. 842-843

Author(s):

V.J.A. Montpetit ◽

S. Dancea ◽

S.W. French ◽

D.F. Clapin

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Model ◽

Paired Helical Filaments ◽

Ethanol Intoxication ◽

Drg Neurons ◽

Critical Difference ◽

Suitable Animal Model ◽

The Central Nervous System ◽

Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

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