phenylephrine-hydrochloride and Cryptococcosis

Topics: Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Humans; Hydroxychloroquine; Male; Mycoses; Nose; Pathology, Molecular; Skin Diseases, Infectious; Young Adult

Cryptococcus neoformans-mediated meningoencephalitis is a critical infectious disorder of the human central nervous system. However, efficient treatment for the disease is limited due to the poor penetration across the blood brain barrier (BBB). Here, we develop a nose-to-brain drug delivery system utilizing nanostructured lipid carriers (NLCs). We demonstrated that fluorescent-dye-loaded NLCs efficiently uptake into the cytoplasm of encapsulated C. neoformans cells. In comparison with current antifungal drugs, the ketoconazole (keto)-NLCs show significantly increased antifungal activity against C. neoformans in vivo under various growth conditions. The NLCs show enhanced tissue colonization properties. Importantly, using animal imaging analyses, NLCs are able to enter brain tissues via the olfactory bulb region by intranasal administration, bypassing the BBB. In addition, NLCs maintain prolonged residence in tissues. In mouse brain tissue, keto-NLCs showed significantly enhanced antifungal activity when administered intranasally, drastically dampening the C. neoformans burden. Taken together, NLCs not only improve the ketoconazole penetration efficiency against capsulated C. neoformans cells, but also boost the efficacy of antifungal drugs. Most importantly, keto-NLCs significantly contribute to the treatment of cryptococcal meningoencephalitis in mice by bypassing the BBB via the olfactory system.

Topics: Administration, Intranasal; Animals; Antifungal Agents; Blood-Brain Barrier; Brain; Cryptococcosis; Cryptococcus neoformans; Drug Carriers; Drug Delivery Systems; Ketoconazole; Lipids; Meningoencephalitis; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Nanostructures; Nose; Particle Size

Cryptococcosis, caused by environmental fungi in the Cryptococcus neoformans and Cryptococcus gattii species complexes, affects a variety of hosts, including koalas (Phascolarctos cinereus). Cryptococcal antigenemia and nasal colonization are well characterized in captive koalas, but free-ranging populations have not been studied systematically. Free-ranging koalas (181) from the Liverpool Plains region of New South Wales, Australia, were tested for cryptococcal antigenemia (lateral flow immunoassay) and nasal colonization (bird seed agar culture). Results were related to environmental and individual koala characteristics. Eucalypt trees (14) were also randomly tested for the presence of Cryptococcus spp. by bird seed agar culture. In sum, 5.5% (10/181) and 6.6% (12/181) of koalas were positive for antigenemia and nasal colonization, respectively, on at least one occasion. And 64.3% (9/14) of eucalypts were culture-positive for Cryptococcus spp. URA5 restriction fragment length polymorphism analysis identified most isolates as C. gattii VGI, while C. neoformans VNI was only found in one koala and one tree. Colonized koalas were significantly more likely to test positive for antigenemia. No associations between antigenemia or colonization, and external environmental characteristics (the relative abundance of Eucalyptus camaldulensis and season), or individual koala characteristics (body condition, sex, and age), could be established, suggesting that antigenemia and colonization are random outcomes of host-pathogen-environment interactions. The relationship between positive antigenemia status and a relatively high abundance of E. camaldulensis requires further investigation. This study characterizes cryptococcosis in a free-ranging koala population, expands the ecological niche of the C. gattii/C. neoformans species complexes and highlights free-ranging koalas as important sentinels for this disease.

Topics: Animals; Animals, Wild; Antigens, Fungal; Asymptomatic Infections; Australia; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Ecosystem; Eucalyptus; Female; Male; Nose; Phascolarctidae; Prevalence

Topics: Cryptococcosis; Humans; Immunocompromised Host; Male; Middle Aged; Multiple Myeloma; Nose; Nose Diseases; Skin Diseases, Bacterial

Cutaneous manifestations of Cryptococcus neoformans in immunocompromised persons have been well documented. We report a case of localized skin involvement after an abrasion in a healthy host. It presented as chronic ulcerative nodules that resolved after fluconazole therapy.

Topics: Aged; Aged, 80 and over; Cryptococcosis; Diagnosis, Differential; Female; Humans; Nose; Nose Diseases

A strain of Cryptococcus neoformans that was isolated from the cerebrospinal fluid of a human diagnosed as having acquired immunodeficiency syndrome (AIDS), and that produced cutaneous lesions in experimentally infected, normal mice is described. Although no unusual cutaneous manifestations were noted in the patient's records, this isolate of C. neoformans proved to be dermotropic when injected intravenously into CD-1 mice. The LD50 at 28 days post infection ranged from 3.6-7.5 X 10(5) cells per mouse, and in vitro growth rate studies demonstrated that this isolate grew well at 35 degrees C and at 37 degrees C, but did not grow at 40 degrees C and higher. This isolate was rhinotropic producing large granulomatous lesions in the nasal tissues. Other cutaneous tissues affected were the periocular tissues, ears, feet and tail, although the granulomas were nodular in structure and less necrotic than the nasal lesions. The brain, lungs, liver, kidneys and spleen also were culture positive for C. neoformans. Histopathologically, each affected tissue examined had large densities of yeast cells and a chronic, granulomatous host response. Animals surviving the infection appeared to develop a commensal-type relationship with the infective yeast. This is the first report of an isolate of C. neoformans from an AIDS patient that has caused cutaneous manifestations in an animal model. The model described in this report may be useful for elucidating pathogenic mechanisms of cryptococcosis, particularly cutaneous manifestations of the disease.

Topics: Acquired Immunodeficiency Syndrome; Adult; Animals; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Dermatomycoses; Disease Models, Animal; Female; Humans; Male; Mice; Nose; Skin

Cryptococcus neoformans was instilled intranasally into mice which were periodically sacrificed to determine the course of infection. Cryptococci persisted within the nasal passages throughout the 90 day study. Extranasal dissemination began 14-28 days after instillation and was still demonstrable 90 days post-exposure. Ten percent mortality was observed in mice receiving 10(6) cryptococci, while no mortality was observed in mice exposed to 10(3) or 10(4) cryptococci. Our research suggests that nasal colonization with C. neoformans can precede pulmonary and systemic cryptococcosis by weeks or months.

Topics: Animals; Brain; Colony Count, Microbial; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Liver; Lung; Male; Mice; Nose; Spleen; Time Factors

An atypical isolate of Cryptococcus neoformans was investigated because of its consistent and reproducible production of gross nasal pathology following i.v. injection in Swiss albino mice. Dose response to graded concentrations ranging from 1 X 10(2)-1 X 10(7) cells/mouse yielded an LD50 of 1.4 X 10(3) cells/mouse for the atypical rhinotropic strain H140 which was significantly less virulent (p less than 0.01) than our reference strain of Cryptococcus neoformans. There was no significant difference in mortality following the injection of in vitro vs. in vivo passed inoculum. As early as two weeks after inoculation, this strain produced gross nasal enlargement to approximately 2-3 X normal dimensions with granulomatous and ulcerated lesions. The LD60 resulted in the greatest percentage of nasal involvement (85%). C. neoformans was demonstrated by culture and histopathology in the noses, brains, lungs, livers and kidneys. A temperature selection was indicated by findings of a lower temperature minimum for subcultures isolated from the noses relative to those isolated from the brain, and by the fact that the most densely populated organs following intraperitoneal injection were the testes. This route of inoculation resulted in cutaneous nasal involvement in a manner analogous to that following i.v. injection. The atypical isolate was unable to assimilate trehalose or raffinose but otherwise was entirely consistent with identification as C. neoformans and produced characteristic CNS and general organ system disease in addition to the rhinotropic cutaneous manifestations. The model characterized here in normal mice may be of value in studies of fungal dermotropism.

Topics: Animals; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Humans; Mice; Nose; Nose Diseases; Organ Specificity

This article discusses the diagnosis and management of acute and chronic diseases of the nasal cavity and sinuses. Also discussed are the anatomy of the upper respiratory tract, guidelines for obtaining a thorough history and performing a complete physical examination, and various diagnostic procedures, such as rhinoscopy, culture, and serology.

Topics: Animals; Cat Diseases; Cats; Cryptococcosis; Dog Diseases; Dogs; Foreign Bodies; Mycoses; Nasopharyngeal Neoplasms; Nose; Nose Diseases; Nose Neoplasms; Paranasal Sinus Diseases; Paranasal Sinus Neoplasms; Polyps; Rhinitis; Sinusitis

Topics: Animals; Cryptococcosis; Cryptococcus neoformans; Female; Frontal Sinus; Horse Diseases; Horses; Nose; Orbit; Turbinates

Topics: Animals; Brain; Chronic Disease; Cryptococcosis; Kidney; Mice; Nose; Skin; Tail