Standing gustatory papillae biopsy procedure for antemortem diagnosis of equine grass sickness.

OBJECTIVE: Diagnosing equine grass sickness (EGS) requires histopathological evidence of chromatolysis and/or neuronal loss in peripheral autonomic ganglia. Previous investigators performed postmortem biopsies of gustatory papillae located on the tongue and found chromatolytic subgemmal neurons in all 13 EGS horses. The present study aimed to design a standardized lingual biopsy sampling method through a transbuccal approach in healthy standing horses and assess the quality of the obtained samples, to allow antemortem diagnosis of EGS in clinical cases. ANIMALS: 6 healthy horses. METHODS: A transbuccal approach was performed bilaterally in 6 healthy standing horses. After having reached a deep level of sedation, horses were placed in stocks and a Günther mouth gag was inserted. Local anesthesia followed by a vertical full thickness incision was performed on both cheeks. Foliate papillae biopsies were carried out using an arthroscopic rongeur inserted through each incision site under oral endoscopic control. Tongue movements were restricted with diazepam. Histological assessment of taste buds and subgemmal plexi neurons was performed using H&E-stained longitudinal sections. RESULTS: The procedure was well tolerated in all horses. Minor complications observed were a transient facial paralysis, some incisional fluid collection, and abscesses. Ten samples (10/12) were suitable for assessment of neuronal perikarya. CLINICAL RELEVANCE: This procedure was safe for subgemmal plexus biopsy in healthy standing horses. The obtained samples were adequate as long as they were neatly cut lengthwise for inclusion. The technique was also used for 2 clinical cases and revealed the complete absence of neuronal perikarya, confirming chronic EGS.

Long-Term Dysfunction of Taste Papillae in SARS-CoV-2.

BACKGROUND: We sought to determine whether ongoing taste disturbance in the postacute sequelae of coronavirus disease 2019 period is associated with persistent virus in primary taste tissue. METHODS: We performed fungiform papillae biopsies on 16 patients who reported taste disturbance lasting more than 6 weeks after molecularly determined severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Then, on multiple occasions, we rebiopsied 10 of those patients who still had taste complaints for at least 6 months postinfection. Fungiform papillae obtained from other patients before March 2020 served as negative controls. We performed hematoxylin and eosin staining to examine fungiform papillae morphology and immunofluorescence and fluorescence in situ hybridization to look for evidence of persistent viral infection and immune response. RESULTS: In all patients, we found evidence of SARS-CoV-2, accompanying immune response and misshapen or absent taste buds with loss of intergemmal neurite fibers. Six patients reported normal taste perception by 6 months postinfection and were not further biopsied. In the remaining 10, the virus was eliminated in a seemingly random fashion from their fungiform papillae, but four patients still, by history, reported incomplete return to preinfection taste perception by the time we wrote this report. CONCLUSIONS: Our data show a temporal association in patients between functional taste, taste papillae morphology, and the presence of SARS-CoV-2 and its associated immunological changes. (Funded by Intramural Research Program/National Institute on Aging/National Institute of Allergy and Infectious Diseases/National Institutes of Health; ClinicalTrials.gov numbers NCT03366168 and NCT04565067.).

Symptomatic subgemmal neurogenous plaque in patients with COVID-19: Is there an association?

BACKGROUND: Subgemmal neurogenous plaques (SNP) are composed of neural structures found in the posterolateral portion of the tongue, rarely biopsied as most of them are asymptomatic or eventually only clinically managed. We aimed to investigate a case series of possible correlation of symptomatic subgemmal neurogenous plaque (SNP) with coronavirus disease 2019 (COVID-19). METHODS: Eleven formalin-fixed paraffin-embedded cases from patients with previous confirmed COVID-19 (by RT-PCR) were retrieved from two pathology files. Histological sections were morphologically studied, and then submitted to immunohistochemical reactions against S-100 and neurofilament proteins, neuron-specific enolase, Glial fibrillary acidic protein (GFAP), synaptophysin, CD56, Ki67, cytokeratins (7, 8-18, 19, 20), nucleocapsid and spike proteins (SARS-CoV-1; and -2) and epithelial membrane antigen (EMA) antibodies. Clinical data were retrieved from the patients' medical files, including the symptoms and the complete history of the progression of the disease. RESULTS: The patients who had COVID-19 included in this study experienced painful lesions in the tongue that corresponded to prominent or altered SNP. Microscopically, neural structures were positive for S-100, GFAP and neurofilament protein. And the cellular proliferative index (by Ki-67) was very low. CONCLUSION: Thus, based on the current results, we hypothesize that symptomatic SNP may be a late manifestation of COVID-19 infection.

Sprague Dawley Rats Gaining Weight on a High Energy Diet Exhibit Damage to Taste Tissue Even after Return to a Healthy Diet.

Many reports detail taste dysfunction in humans and animals with obesity. For example, mice consuming an obesogenic diet for a short period have fewer taste buds than their lean littermates. Further, rats with diet-induced obesity (DIO) show blunted electrophysiological responses to taste in the brainstem. Here, we studied the effects of high energy diet (HED)-induced peripheral taste damage in rats, and whether this deficiency could be reversed by returning to a regular chow diet. Separate groups of rats consumed a standard chow diet (Chow), a HED for 10 weeks followed by a return to chow (HED/chow), or a HED for 10 weeks followed by a restricted HED that was isocaloric with consumption by the HED/chow group (HED/isocal). Fungiform taste papilla (FP) and circumvallate taste bud abundance were quantified several months after HED groups switched diets. Results showed that both HED/chow and HED/isocal rats had significantly fewer FP and lower CV taste bud abundance than control rats fed only chow. Neutrophil infiltration into taste tissues was also quantified, but did not vary with treatment on this timeline. Finally, the number of cells undergoing programmed cell death, measured with caspase-3 staining, inversely correlated with taste bud counts, suggesting taste buds may be lost to apoptosis as a potential mechanism for the taste dysfunction observed in obesity. Collectively, these data show that DIO has lasting deleterious effects on the peripheral taste system, despite a change from a HED to a healthy diet, underscoring the idea that obesity rather than diet predicts damage to the taste system.

The umami receptor T1R1-T1R3 heterodimer is rarely formed in chickens.

The characterization of molecular mechanisms underlying the taste-sensing system of chickens will add to our understanding of their feeding behaviors in poultry farming. In the mammalian taste system, the heterodimer of taste receptor type 1 members 1/3 (T1R1/T1R3) functions as an umami (amino acid) taste receptor. Here, we analyzed the expression patterns of T1R1 and T1R3 in the taste cells of chickens, labeled by the molecular markers for chicken taste buds (vimentin and α-gustducin). We observed that α-gustducin was expressed in some of the chicken T1R3-positive taste bud cells but rarely expressed in the T1R1-positive and T2R7-positive taste bud cells. These results raise the possibility that there is another second messenger signaling system in chicken taste sensory cells. We also observed that T1R3 and α-gustducin were expressed mostly in the vimentin-positive taste bud cells, whereas T1R1 and bitter taste receptor (i.e., taste receptor type 2 member 7, T2R7) were expressed largely in the vimentin-negative taste bud cells in chickens. In addition, we observed that T1R1 and T1R3 were co-expressed in about 5% of chickens' taste bud cells, which express T1R1 or T1R3. These results suggest that the heterodimer of T1R1 and T1R3 is rarely formed in chickens' taste bud cells, and they provide comparative insights into the expressional regulation of taste receptors in the taste bud cells of vertebrates.

Human Type II Taste Cells Express Angiotensin-Converting Enzyme 2 and Are Infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Chemosensory changes are well-reported symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The virus targets cells for entry by binding of its spike protein to cell-surface angiotensin-converting enzyme 2 (ACE2). It is not known whether ACE2 is expressed on taste receptor cells (TRCs), or whether TRCs are infected directly. in situ hybridization probe and an antibody specific to ACE2 indicated presence of ACE2 on a subpopulation of TRCs (namely, type II cells in taste buds in taste papillae). Fungiform papillae of a SARS-CoV-2+ patient exhibiting symptoms of coronavirus disease 2019 (COVID-19), including taste changes, were biopsied. Presence of replicating SARS-CoV-2 in type II cells was verified by in situ hybridization. Therefore, taste type II cells provide a potential portal for viral entry that predicts vulnerabilities to SARS-CoV-2 in the oral cavity. The continuity and cell turnover of a patient's fungiform papillae taste stem cell layer were disrupted during infection and had not completely recovered 6 weeks after symptom onset. Another patient experiencing post-COVID-19 taste disturbances also had disrupted stem cells. These results demonstrate the possibility that novel and sudden taste changes, frequently reported in COVID-19, may be the result of direct infection of taste papillae by SARS-CoV-2. This may result in impaired taste receptor stem cell activity and suggest that further work is needed to understand the acute and postacute dynamics of viral kinetics in the human taste bud.

Smell and taste disorders in COVID-19: From pathogenesis to clinical features and outcomes.

Patients with COVID-19 often complain of smell and taste disorders (STD). STD emerge early in the course of the disease, seem to be more common in SARS-CoV-2 infection than in other upper respiratory tract infections, and could in some cases persist for long after resolution of respiratory symptoms. Current evidence suggests that STD probably result from a loss of function of olfactory sensory neurons and taste buds, mainly caused by infection, inflammation, and subsequent dysfunction of supporting non-neuronal cells in the mucosa. However, the possible occurrence of other mechanisms leading to chemosensory dysfunction has also been hypothesized, and contrasting data have been reported regarding the direct infection of sensory neurons by SARS-CoV-2. In this mini-review, we summarize the currently available literature on pathogenesis, clinical manifestations, diagnosis, and outcomes of STD in COVID-19 and discuss possible future directions of research on this topic.

Anatomical features of the tongue of two chiropterans endemic in the Egyptian fauna; the Egyptian fruit bat (Rousettus aegyptiacus) and insectivorous bat (Pipistrellus kuhlii).

The current study aimed to investigate the tongue (lingual) morphometry, histology, and histochemistry of two chiropterans endemic in the Egyptian fauna, and having different feeding preferences. The tongues of nine adult individuals of each species were utilized in our investigation. The tongue of fruit-eating bat was observed relatively longer than the one of insect-eating bat. Grossly, the insect-eating bat had a lingual prominence on the dorsum of lingual body, while the fruit-eating bat had a concave midline over the lingual body. Histologically, numerous forms of lingual papillae were scattered along the dorsal epithelium of the tongue. The lingual papillae of the fruit-eating bat seem to be well adapted for piercing the skin of a fruit and liquid sap retention. The lingual glands of both species were lodged in the muscular layer. Two main sets were identified; the serous von Ebner's gland usually seen accompanied by the circumvallate papillae and Weber's gland with mixed mucoserous secretions. Von Ebner's gland showed more prominent acidic mucins, while Weber's gland expressed neutral mucins. The lingual epithelium of the fruit-eating bat had an outer covering of cornified non-nucleated epithelium. On the other hand, the insect-eating bat had an outer covering of nucleated epithelium. It is for the first time to record the existence of the entoglossal plates of both species which consisted of a bony core in the fruit-eating bat and a cartilaginous element in the insect-eating bat. The current study represents an attempt to shed more light on the tongue evolution among mammalian vertebrates.

Taste loss with obesity in mice and men.

BACKGROUND: Our sense of taste is critical in defining our food choices and habits. Located primarily in our tongue, taste buds are small assemblies of constantly renewing sensory cells, tasked with evaluating oral stimuli before the food we eat is consumed. METHODS: Using both mice and a free-living human population, we tracked taste papilla abundancy with weight gain, to test for deficiencies in the taste system of obese mice and humans with increased adiposity. RESULTS: Mice fed a high-fat diet for 8 weeks expressed markers for all subtypes of taste cells at a lower level than chow-fed counterparts. This came alongside the loss of markers for taste cell proliferation (Ki-67) and development (ß-catenin), as well as lower fungiform papillae density, consistent with earlier results showing lower circumvallate taste bud abundance in obese mice. Likewise, in a population of college students tracked through 4 years of college attendance, the change in density of fungiform papillae, which house taste buds in the anterior tongue, was negatively correlated with change in neck circumference, a marker of adiposity. CONCLUSIONS: These results highlight changes in taste during weight gain as a potentially important consideration in the study of obesity.

Papilas Fungiformes Pigmentadas de la Lengua. Características Clínicas, Histológicas y Dermatoscópicas de una Serie de Casos Ecuatorianos / Pigmented Fungiform Papillae of the Tongue. Clinical, Histological and Dermatoscopic Characteristics A Serie of Ecuadorian Cases

RESUMEN: Las papilas fungiformes pigmentadas de la lengua, cuyas siglas son PFPT, del inglés Pigmented fungiform papillae of the tongue, es una condición asintomática, no progresiva que se presenta en personas de piel oscura, en las cuales las papilas fungiformes cambian de su color rosado natural, a una gama de café a negro. El objetivo de nuestro estudio es reportar y describir las caractetísticas clínicas, dermatoscópicas e histológicas de la PFPT por primera vez en una serie de pacientes ecuatorianos. Estudio prospectivo simple en el Centro de Especialidades Dermatológicas Garzón, período de dos años. El criterio de inclusión fue cambio de coloración a nivel lingual, se recolectaron datos demográficos, clínicos; fotografías, dermatoscopía, y biopsia, para tinción con hematoxilina-eosina y Fontana-Mason. Examinamos 8.640 pacientres, 15 (12 mujeres, 3 varones) fueron diagnosticados de PFPT. La edad promedio fue 31 años, todos fueron mestizos, con fototipo de piel predominante III y IV. El tiempo de evolución promedio en años fue 5,8. Ninguno tuvo antescedentes familiares o personales relacionados a la patología. La evaluación clínica demostró que el patrón de distribución de acuerdo a la clasificación de Holzwanger en la gran mayoría fue tipo II (13/15). En todos los casos la dermatoscopía y la histología fueron específicas demostrando hallazgos típicos y comprobatorios de PFPT.

ABSTRACT: The pigmented fungiform papillae of the tongue, whose acronyms are PFPT, of the English Pigmented fungiform papillae of the tongue, is an asymptomatic, nonprogressive condition that occurs in dark-skinned people, in which the fungiform papillae change their color natural pink, to a range of brown to black. The aim of our study is to report and describe the clinical, dermatoscopic and histological characteristics of the PFPT for the first time in a series of Ecuadorian patients. A simple prospective study at the Garzón Dermatological Specialty Center, a two-year period. The inclusion criteria was lingual change of color, demographic, clinical data were collected; photographs, dermatoscopy, and biopsy, for staining with hematoxylin-eosin and FontanaMason. We examined 8,640 patients, 15 (12 women, 3 men) were diagnosed with PFTP. The range of age was 31 years, all were mestizos, with skin phototype predominant III and IV. The range of evolution time in years was 5.8. None had family or personal precedents related to the pathology. The clinical evaluation showed that the pattern of distribution according to the Holzwanger classification in the great majority was type II (13/15). In all cases, the dermatoscopy and histology were specific, demonstrating typical and evidential findings of PFPT.

Pigmented fungiform papillae of the tongue: a clinical and histologic description.

A 28-year-old man with a history of mycosis fungoides presented for evaluation of multiple dark-brown macules and hyperpigmented dome-shaped papules on the distal tongue. A shave biopsy of the tongue revealed melanin pigment in the basal keratinocytes and melanophages in the lamina propria, consistent with pigmented fungiform papillae of the tongue. Relevant clinical and histologic features of this diagnosis are reviewed.

Cyclophosphamide and the taste system: Effects of dose fractionation and amifostine on taste cell renewal.

Chemotherapy often causes side effects that include disturbances in taste functions. Cyclophosphamide (CYP) is a chemotherapy drug that, after a single dose, elevates murine taste thresholds at times related to drug-induced losses of taste sensory cells and disruptions of proliferating cells that renew taste sensory cells. Pretreatment with amifostine can protect the taste system from many of these effects. This study compared the effects of a single dose (75 mg/kg) of CYP with effects generated by fractionated dosing of CYP (5 doses of 15 mg/kg), a dosing approach often used during chemotherapy, on the taste system of mice using immunohistochemistry. Dose fractionation prolonged the suppressive effects of CYP on cell proliferation responsible for renewal of taste sensory cells. Fractionation also reduced the total number of cells and the proportion of Type II cells within taste buds. The post-injection time of these losses coincided with the life span of Type I and II taste cells combined with lack of replacement cells. Fractionated dosing also decreased Type III cells more than a single dose, but loss of these cells may be due to factors related to the general health and/or cell renewal of taste buds rather than the life span of Type III cells. In general, pretreatment with amifostine appeared to protect taste cell renewal and the population of cells within taste buds from the cytotoxic effects of CYP with few observable adverse effects due to repeated administration. These findings may have important implications for patients undergoing chemotherapy.

A pathological study of the tongues of rabid dogs in the Philippines.

During rabies virus infections, the minor salivary glands are one of the important organs for virus replication and excretion into the oral cavity. However, details of pathological findings and viral antigen distribution in the minor salivary glands remain poorly understood. In this study, we conducted pathological tests on the tongues of 71 rabid dogs in the Philippines; the minor salivary glands (von Ebner's glands, lingual glands), circumvallate papilla, autonomic ganglia, and skeletal muscles were evaluated. Inflammatory changes were observed in the von Ebner's glands of 20/71 dogs, in the circumvallate papilla of 10/71, and in the tongue muscle of 1/71. Conversely, no morphological changes were observed in the lingual glands and autonomic ganglia. Viral antigens were detected via immunohistochemistry-based methods in the cytoplasm of the acinar epithelium in the von Ebner's glands of all 71 dogs. Virus particles were confirmed in the intercellular canaliculi and acinar lumen via electron microscopy. In the autonomic ganglia, viral antigens were detected in 67/71 rabid dogs. Viral antigens were detected in the taste buds of all 71 dogs, and were distributed mainly in type II and III taste bud cells. In tongue muscle fibers, viral antigens were detected in 11/71 dogs. No virus antigens were detected in lingual glands. These findings suggest that rabies virus descends in the tongue along the glossopharyngeal nerve after proliferation in the brain, and von Ebner's glands and taste buds are one of the portals of virus excretion into the saliva in rabid dogs.

Inflammation arising from obesity reduces taste bud abundance and inhibits renewal.

Despite evidence that the ability to taste is weakened by obesity and can be rescued with weight loss intervention, few studies have investigated the molecular effects of obesity on the taste system. Taste bud cells undergo continual turnover even in adulthood, exhibiting an average life span of only a few weeks, tightly controlled by a balance of proliferation and cell death. Recent data reveal that an acute inflammation event can alter this balance. We demonstrate that chronic low-grade inflammation brought on by obesity reduces the number of taste buds in gustatory tissues of mice-and is likely the cause of taste dysfunction seen in obese populations-by upsetting this balance of renewal and cell death.

Pigmented fungiform lingual papillae: dermoscopic and clinical features.

The tongue is covered by fungiform, filiform and circumvallate papillae. Fungiform papillae may be mainly pigmented in dark-skinned individuals. A single-centre study aimed to examine the clinical and dermoscopic features of pigmented fungiform papulae of the tongue (PFPT) in children, and a concise review of the literature has been performed. The clinical and anamnestic data of eight children affected by PFPT visited at the Pediatric Dermatology Unit of Bologna between 2010 and 2017, and a systemic review of all studies of PFPT published on PubMed up to 31 August 2017 has been collected and analysed. The results of our data were consistent with the literature review: dark brown to black coloured pinhead papules or bumps were observed in all cases of PFPT, and three types of clinical patterns have been detected. Moreover, the dermoscopic examination showed a cobblestone-like distribution and rose petal pattern. PFPT could be associated with hyperpigmentation of other sites such as the proximal nail folds and gums, and an intrafamiliar transmission is also possible. Clinical and dermoscopic features of PFPT may help clinicians to recognize this ethnic, acquired and benign condition.

Chk2 deficiency alleviates irradiation-induced taste dysfunction by inhibiting p53-dependent apoptosis.

OBJECTIVE: Taste dysfunction is one of the most common complications following radiotherapy, which leads to decreased appetite and life quality of patients suffering from head and neck cancer. The aim of this study was to investigate the role of checkpoint kinase 2 (Chk2) deficiency in irradiation-induced taste dysfunction. MATERIALS AND METHODS: Alterations in oxidative stress, DNA damage, and potential signaling pathway were compared between Chk2-deficient (Chk2-/- ) mice and their wild-type (WT) littermates pre-irradiation and 7 and 30 days postirradiation by biochemistry and immunohistochemistry. RESULTS: Chk2-/- mice showed less loss of type II and type III taste cells, lower expression of p53, caspase-3, and cleaved caspase-3, and lower apoptosis levels. However, no significant differences in H2 O2 and MDA concentrations, T-SOD and GSH-Px activities, and expression of SOD1, SOD2, and 8-OHdG were detected in the taste buds of Chk2-/- mice as compared to those of WT mice. CONCLUSION: Chk2 deficiency downregulated the expression of p53 and inhibited cellular apoptosis, partly contributing to the radioprotective effect on taste cells, but did not alter oxidative stress levels, antioxidant ability, and oxidative DNA damage in taste buds.

Unilateral nasal obstruction induces degeneration of fungiform and circumvallate papillae in rats.

BACKGROUND: In clinical orthodontic treatment, chronic respiratory disturbance or mouth breathing has been concerned symptoms and screening criteria. In this study, to analyze the relation between nasal obstruction and taste sensing, a unilateral nasal obstruction model was performed to investigate the taste papillae and taste buds in rats. METHODS: Fourteen 6-day-old male Wistar rats were randomly divided into control and experimental groups (n = 7 each). The experimental group underwent unilateral nasal obstruction at 8 days of age. The rats were euthanized at 9-week-old. The morphology of the circumvallate papillae and taste buds were identified by immunohistochemical methods. The fungiform papillae were visualized with 1% methylene blue and sectioned for taste bud observation. RESULTS: Some defects in the gustatory epithelium were observed after unilateral nasal obstruction. Rats in the experimental group had significantly fewer fungiform papillae and smaller volumes of taste bud. In circumvallate papillae, smaller total taste bud area was found in experiment group. CONCLUSION: Findings in the present study suggest that nasal obstruction might have significant influences on the gustatory function via morphologic change in the taste papillae and taste buds in tongue area.

Recovery of taste organs and sensory function after severe loss from Hedgehog/Smoothened inhibition with cancer drug sonidegib.

Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO signaling inhibition. Sonidegib treatment led to rapid loss of taste buds (TB) in both fungiform and circumvallate papillae, including disruption of TB progenitor-cell proliferation and differentiation. Effects were selective, sparing nontaste papillae. To confirm that taste-organ effects of sonidegib treatment result from HH/SMO signaling inhibition, we studied mice with conditional global or epithelium-specific Smo deletions and observed similar effects. During sonidegib treatment, chorda tympani nerve responses to lingual chemical stimulation were maintained at 10 d but were eliminated after 16 d, associated with nearly complete TB loss. Notably, responses to tactile or cold stimulus modalities were retained. Further, innervation, which was maintained in the papilla core throughout treatment, was not sufficient to sustain TB during HH/SMO inhibition. Importantly, treatment cessation led to rapid and complete restoration of taste responses within 14 d associated with morphologic recovery in about 55% of TB. However, although taste nerve responses were sustained, TB were not restored in all fungiform papillae even with prolonged recovery for several months. This study establishes a physiologic, selective requirement for HH/SMO signaling in taste homeostasis that includes potential for sensory restoration and can explain the temporal recovery after taste dysgeusia in patients treated with HH/SMO inhibitors.