Rinolitiase: Atualizacao e relato de caso

Rhinoliths are rares and, in general, develop in response to foreign body lodged in the nose. This study briefly comments the clinics features of one case of rhinolithiasis that occurred during two years period. The etiology of rinoliths, differencial diagnosis and a review of the literature are also included. The authors concluded that the presence of calcified stones must be considered in cases of sinusitis or rhinitis not responding to medical therapy.

The use of bone scintigraphy to detect active Hansen's disease in mutilated patients

Mutilation of extremities was very frequent in patients affected by leprosy in the past; although it is now much less common, it is still seen, mainly in patients with long-term disease. In general, mutilation of the nose and ears is caused by the bacillus and mutilation of the hands and feet a consequence of chronic trauma. Leprosy must be chronically treated and any decision to interrupt therapy is based on laboratory tests and biopsy. Scintigraphy is a non-invasive procedure which could be of great value in to determining disease activity. We studied eight patients (five males and three females, aged 64-73 years) who presented with mutilation of the nose (2), ear (1), feet (3) or foot and hand (2), Conventional three-phase bone scintigraphy (750 MBq) and X-ray examinations of the affected areas were performed in all patients. Bone scintigraphy was abnormal in four patients (the presence of bacilli was confirmed by biopsy in two of them), and normal in the other four. In all patients except for the one with ear mutilation, radiography only showed the absence of bone. We conclude that bone scintigraphy is very useful to determine disease activity in cases of mutilation caused by leprosy. It seems to be superior to conventional radiography and may enable bone biopsies to be avoided.

Ligature of external carotid artery as an optional technique in a patient with von Willebrand disease

The von Willebrand disease (vWD) is a hereditary coagulopathy. There is no gender predilection. Clinically characterized by mucocutaneous bleeding, especially nose bleeding, menorrhagia and bleeding after trauma. This article reports a case of a 52-year-old Caucasian male patient with vWD, who presented with extensive bleeding in the tongue after a lacerating injury caused by accidental biting, and describes some clinical, pathological and treatment aspects of vWD. After repeated attempts to suture the wound and replace clotting factors, a decision was made to perform the ligature of the external carotid artery ipsilateral to the injury. There was favorable resolution of the case, with a good aspect of the scar 2 months after ligation. This case reinforces that it is extremely important to make a thorough review of medical history of all patients, searching for possible bleeding disorders or previous family history.

Nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease

Alzheimer's disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood-brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease.

Experimental Infection of Bats with Geomyces destructans Causes White-nose Syndrome

White-nose syndrome (WNS) has caused recent catastrophic declines among multiple species of bats in eastern North America1, 2. The disease’s name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin (including the muzzle) of hibernating bats1, 3. Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS4. However, the role of G. destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking. The debate is fuelled, in part, by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction5, 6, 7. Additionally, the recent discovery that G. destructans commonly colonizes the skin of bats of Europe, where no unusual bat mortality events have been reported8, 9, 10, has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS11, 12. Here we demonstrate that exposure of healthy little brown bats (Myotis lucifugus) to pure cultures of G. destructans causes WNS. Live G. destructans was subsequently cultured from diseased bats, successfully fulfilling established criteria for the determination ofG. destructans as a primary pathogen13. We also confirmed that WNS can be transmitted from infected bats to healthy bats through direct contact. Our results provide the first direct evidence that G. destructans is the causal agent of WNS and that the recent emergence of WNS in North America may represent translocation of the fungus to a region with a naive population of animals8. Demonstration of causality is an instrumental step in elucidating the pathogenesis14 and epidemiology15 of WNS and in guiding management actions to preserve bat populations against the novel threat posed by this devastating infectious disease.

Frequent Arousal from Hibernation Linked to Severity of Infection and Mortality in Bats with White-Nose Syndrome

White-nose syndrome (WNS), an emerging infectious disease that has killed over 5.5 million hibernating bats, is named for the causative agent, a white fungus (Geomyces destructans (Gd)) that invades the skin of torpid bats. During hibernation, arousals to warm (euthermic) body temperatures are normal but deplete fat stores. Temperature-sensitive dataloggers were attached to the backs of 504 free-ranging little brown bats (Myotis lucifugus) in hibernacula located throughout the northeastern USA. Dataloggers were retrieved at the end of the hibernation season and complete profiles of skin temperature data were available from 83 bats, which were categorized as: (1) unaffected, (2) WNS-affected but alive at time of datalogger removal, or (3) WNS-affected but found dead at time of datalogger removal. Histological confirmation of WNS severity (as indexed by degree of fungal infection) as well as confirmation of presence/absence of DNA from Gd by PCR was determined for 26 animals. We demonstrated that WNS-affected bats aroused to euthermic body temperatures more frequently than unaffected bats, likely contributing to subsequent mortality. Within the subset of WNS-affected bats that were found dead at the time of datalogger removal, the number of arousal bouts since datalogger attachment significantly predicted date of death. Additionally, the severity of cutaneous Gd infection correlated with the number of arousal episodes from torpor during hibernation. Thus, increased frequency of arousal from torpor likely contributes to WNS-associated mortality, but the question of how Gd infection induces increased arousals remains unanswered.

White-Nose Syndrome-Affected Litttle Brown Myotis (Myotis Lucifugus) Increase Grooming and Other Active Behaviors During Arousals from Hibernation

White-nose syndrome (WNS) is an emerging infectious disease of hibernating bats linked to the death of an estimated 5.7 million or more bats in the northeastern United States and Canada. White-nose syndrome is caused by the cold-loving fungus Pseudogymnoascus destructans (Pd), which invades the skin of the muzzles, ears, and wings of hibernating bats. Previous work has shown that WNS-affected bats arouse to euthermic or near euthermic temperatures during hibernation significantly more frequently than normal and that these too-frequent arousals are tied to severity of infection and death date. We quantified the behavior of bats during these arousal bouts to understand better the causes and consequences of these arousals. We hypothesized that WNS-affected bats would display increased levels of activity (especially grooming) during their arousal bouts from hibernation compared to WNS-unaffected bats. Behavior of both affected and unaffected hibernating bats in captivity was monitored from December 2010 to March 2011 using temperature-sensitive dataloggers attached to the backs of bats and infrared motion-sensitive cameras. The WNS-affected bats exhibited significantly higher rates of grooming, relative to unaffected bats, at the expense of time that would otherwise be spent inactive. Increased self-grooming may be related to the presence of the fungus. Elevated activity levels in affected bats likely increase energetic stress, whereas the loss of rest (inactive periods when aroused from torpor) may jeopardize the ability of a bat to reestablish homeostasis in a number of physiologic systems.

Electrolyte Depletion in White-nose Syndrome Bats

The emerging wildlife disease white-nose syndrome is causing widespread mortality in hibernating North American bats. White-nose syndrome occurs when the fungus Geomyces destructans infects the living skin of bats during hibernation, but links between infection and mortality are underexplored. We analyzed blood from hibernating bats and compared blood electrolyte levels to wing damage caused by the fungus. Sodium and chloride tended to decrease as wing damage increased in severity. Depletion of these electrolytes suggests that infected bats may become hypotonically dehydrated during winter. Although bats regularly arouse from hibernation to drink during winter, water available in hibernacula may not contain sufficient electrolytes to offset winter losses caused by disease. Damage to bat wings from G. destructans may cause life-threatening electrolyte imbalances.

Diagnostic value of biopsies in identifying cytoplasmic antineutrophil cytoplasmic antibody-negative localized Wegener's granulomatosis presenting primarily with sinonasal disease

A substantial proportion of Wegener's disease (WG) patients present with localized disease of the upper airways, i.e., sinonasal and other ear/nose/throat (ENT) symptoms. Because of the oligosymptomatic presentation a timely diagnosis of this potentially fatal disease is challenging. This study evaluates diagnostic peculiarities between WG in its localized and generalized form of the disease.

Hibernacula Microclimate and White-nose Syndrome Susceptibility in the Little Brown Myotis (Myotis lucifugus)

The objective of this project was to determine the relationship between hibernacula microclimate and White-nose Syndrome (WNS), an emerging infectious disease in bats. Microclimate was examined on a species scale and at the level of the individual bat to determine if there was a difference in microclimate preference between healthy and WNS-affected little brown myotis (Myotis lucifugus) and to determine the role of microclimate in disease progression. There is anecdotal evidence that colder, drier hibernacula are less affected by WNS. This was tested by placing rugged temperature and humidity dataloggers in field sites throughout the eastern USA, experimentally determining the response to microclimate differences in captive bats, and testing microclimate roosting preference. This study found that microclimate significantly differed from the entrance of a hibernaculum versus where bats traditionally roost. It also found hibernaculum temperature and sex had significant impacts on survival in WNS-affected bats. Male bats with WNS had increased survivability over WNS-affected female bats and WNS bats housed below the ideal growth range of the fungus that causes WNS, Geomyces destructans, had increased survival over those housed at warmer temperatures. The results from this study are immediately applicable to (1) predict which hibernacula are more likely to be infected next winter, (2) further our understanding of WNS, and (3) determine if direct mitigation strategies, such as altering the microclimate of mines, will be effective ways to combat the spread of the fungus.

Altered Behavior in Bats Affected by White-Nose Syndrome

WNS-affected bats did so over similar time frames as WNSunaffected bats. The behaviors of bats with WNS did not change as drastically as expected. Thereseems to be little to no effect on their ability to fly/forage until much later stages of the disease when they are likely near death. WNS-affected bats are grooming more which could be altering the way they use energy reserves during hibernation possibly leading tostarvation and eventually death. The decreased likelihood of arousals in response to external cues may be the result of spending more energy during previous and increasingly frequent arousals. While it is clear that WNS does result in changes in behavior whether these changes are directly in response to fungal skin infection or to some other component of the syndrome such as decreased energy availability or loss of homeostasis is unknown. bat behavior, white-nose syndrome, behavior, video surveillance, arousal patterns White-Nose Syndrome (WNS) is a disease of hibernating bats caused by the fungal pathogen Geomyces destructans. The fungus, which was first noted in 2006, invades bats wings and other exposed membranes, eventually resulting in death. Researchers have yet to understand many aspects of this disease, including basic etiology and epidemiology. There is also a lack of information on how fungal infection may change the behavior of healthy bats during hibernation or how changes in behavior may influence disease progression. Based upon the physiological changes that are known to occur in affected bats, and upon anecdotal observations of aberrant behavior in these bats, I hypothesized that WNS would significantly change the behavior of the little brown myotis (Myotis lucifugus). My research examined the behavior of hibernating bats during arousals from torpor. I compared WNS-affected and unaffected bats, in the field and incaptivity, using motion-sensitive infrared cameras. Flight maneuverability and echolocation were also tested between WNS-affected and unaffected bats during arousalsfrom hibernation to detect changes in the bats' ability to perform basic locomotion or potentially catch insect prey. Lastly, hibernating bats were artificially disturbed and theirarousal patterns were monitored to examine changes in the response to external stimuli between WNS-affected and unaffected bats.Bats with WNS groomed for longer periods of time after arousing from torpor, both in the field and in captivity. They also engaged in longer periods of any sort of activity during these arousals. There were no changes in acoustical signaling during flight tests and changes in flight maneuverability were only found in bats were seen staging" near the entrance of the mine which is itself a unique behavior exhibited by affected bats. At this point these bats were likely near death and could barely fly at all. In response toexternal stimuli bats with WNS were less likely to arouse than unaffected bats. However when they did arouse WNS-affected bats did so over similar time frames as WNSunaffected bats. The behaviors of bats with WNS did not change as drastically as expected. Thereseems to be little to no effect on their ability to fly/forage until much later stages of the disease when they are likely near death. WNS-affected bats are grooming more which could be altering the way they use energy reserves during hibernation possibly leading tostarvation and eventually death. The decreased likelihood of arousals in response to external cues may be the result of spending more energy during previous and increasingly frequent arousals. While it is clear that WNS does result in changes in behavior whetherthese changes are directly in response to fungal skin infection or to some other component of the syndrome such as decreased energy availability or loss of homeostasis is unknown."

Physiological Consequences Of White-Nose Syndrome

White-nose syndrome (WNS) is a disease that has caused the mass mortality of hibernating bat species. Since its first discovery in the winter of 2006-2007, an estimated five million bats or more have been killed. Although infection with Pseudogymnoascus destructans (Pd, the causative agent of WNS) does not always result in death, bats that survive Pd infection may experience fitness consequences. To understand the physiological consequences of WNS, I measured reproductive rates of free-ranging hibernating bat species of the Northeastern United States. In addition, captive little brown myotis (Myotis lucifugus) bats that were infected by Pd but survived (¿WNS survivors¿) and uninfected bats were studied in order to understand the potential consequences (e.g., lower reproductive rates, decreased ability to heal wounds, degradation of wing tissue, and altered metabolic rates) of surviving WNS. No differences in reproductive rates were found between WNS-survivors and uninfected bats in either the field or in captivity. In addition, wound healing was not affected by Pd infection. However, wing tissue degradation was worse for little brown myotis 19 days post-hibernation, and mass specific metabolic rate (MSMR) was significantly higher for those infected with Pd 22 days post-hibernation. While it is clear that these consequences are a direct result of Pd infection, further research investigating the long-term consequences for both mothers and pups is necessary.

Exploration Of Survival Traits In The White-Nose Syndrome-Affected Big Brown Bat (Eptesicus Fuscus)

The widespread mortality of hibernating bats is associated with the emerging infectious disease white-nose syndrome (WNS), and has provoked a strong interest in understanding which bats will survive, and why? The ability of infected bats to resist WNS may depend upon variation in the expression of different characteristics. In a captive colony of big brown bats, I sought to characterize the phenotypic variability, repeatability, and survivability for several key ¿survival¿ traits, including: torpor patterns, microclimate preferences, and wound healing capacity. Torpor patterns were profiled using temperature sensitive dataloggers throughout the hibernation season, while microclimate preferences were quantified by using temperature-graded boxes and thermal imaging. In order to assess wound healing capacity, small wing biopsies were obtained from each bat and healing progress was tracked for one month. Individuals exhibited a wide range of phenotypes that were significantly influenced by sex and body condition. Repeatability estimates suggest that there is not a strong genetic basis for the observed variation in torpor patterns or microclimate preferences. Certain phenotypes (e.g., BMI) were associated with an increased probability of overwinter survivorship, which suggests a basis for intra-species differences in WNS susceptibility. The results from this project provide novel insight into what we know about ¿who will survive,¿ and will influence the direction and implementation of future conservation and mitigation strategies.

Nonlethal Screening of Bat-Wing Skin with the Use of Ultraviolet Fluorescence to Detect Lesions Indicative of White-Nose Syndrome

Definitive diagnosis of the bat disease white-nose syndrome (WNS) requires histologic analysis to identify the cutaneous erosions caused by the fungal pathogen Pseudogymnoascus [formerly Geomyces] destructans (Pd). Gross visual inspection does not distinguish bats with or without WNS, and no nonlethal, on-site, preliminary screening methods are available for WNS in bats. We demonstrate that long-wave ultraviolet (UV) light (wavelength 366-385 nm) elicits a distinct orange yellow fluorescence in bat-wing membranes (skin) that corresponds directly with the fungal cupping erosions in histologic sections of skin that are the current gold standard for diagnosis of WNS. Between March 2009 and April 2012, wing membranes from 168 North American bat carcasses submitted to the US Geological Survey National Wildlife Health Center were examined with the use of both UV light and histology. Comparison of these techniques showed that 98.8% of the bats with foci of orange yellow wing fluorescence (n=80) were WNS-positive based on histologic diagnosis; bat wings that did not fluoresce under UV light (n=88) were all histologically negative for WNS lesions. Punch biopsy samples as small as 3 mm taken from areas of wing with UV fluorescence were effective for identifying lesions diagnostic for WNS by histopathology. In a nonlethal biopsy-based study of 62 bats sampled (4-mm diameter) in hibernacula of the Czech Republic during 2012, 95.5% of fluorescent (n=22) and 100% of nonfluorescent (n=40) wing samples were confirmed by histopathology to be WNS positive and negative, respectively. This evidence supports use of long-wave UV light as a nonlethal and field-applicable method to screen bats for lesions indicative of WNS. Further, UV fluorescence can be used to guide targeted, nonlethal biopsy sampling for follow-up molecular testing, fungal culture analysis, and histologic confirmation of WNS.

Thymus transplantation, a critical factor for correction of autoimmune disease in aging MRL/+mice.

MRL/MP-+/+ (MRL/+) mice develop pancreatitis and sialoadenitis after they reach 7 months of age. Conventional bone marrow transplantation has been found to be ineffective in the treatment of these forms of apparent autoimmune disease. Old MRL/+ mice show a dramatic thymic involution with age. Hematolymphoid reconstitution is incomplete when fetal liver cells (as a source of hemopoietic stem cells) plus fetal bone (FB; which is used to recruit stromal cells) are transplanted from immunologically normal C57BL/6 donor mice to MRL/+ female recipients. Embryonic thymus from allogeneic C57BL/6 donors was therefore engrafted along with either bone marrow or fetal hematopoietic cells (FHCs) plus fragments of adult or fetal bone. More than seventy percent of old MRL/+ mice (> 7 months) that had been given a fetal thymus (FT) transplant plus either bone marrow or FHCs and also bone fragments survived more than 100 days after treatment. The mice that received FHCs, FB, plus FT from allogeneic donors developed normal T cell and B cell functions. Serum amylase levels decreased in these mice whereas they increased in the mice that received FHCs and FB but not FT. The pancreatitis and sialoadenitis already present at the time of transplantations were fully corrected according to histological analysis by transplants of allogeneic FHCs, FB and FT in the MRL/+ mice. These findings are taken as an experimental indication that perhaps stem cell transplants along with FT grafts might represent a useful strategy for treatment of autoimmune diseases in aged humans.