Brochure intervention to manage bothersome taste changes in pediatric patients receiving cancer therapy.

BACKGROUND: Primary objective was to determine if a patient informational brochure describing potentially useful strategies could help manage specific taste changes. Secondary objective was to describe the specific strategies used and whether the strategies were perceived as being helpful. PROCEDURE: This single-center study included pediatric patients with cancer or hematopoietic cell transplant recipients receiving active treatment who experienced bothersome taste changes in the last month. Participants participated in baseline and follow-up interviews conducted 14-21 days apart. A brochure that listed 16 potentially helpful strategies was provided at baseline. At follow-up, we asked about brochure use and whether it helped. At both interviews, we asked about experienced taste changes, strategies used, and whether strategy helped. RESULTS: Of 100 enrolled participants, different (87%) and bad (72%) taste were most common at baseline. Following the brochure intervention, statistically significant reductions were observed in food tasting different, bad, bland, bitter, sour, and metallic. For most strategies, the proportion of patients who used specific strategies or found them helpful was not significantly different between baseline and follow-up. However, "eating foods you like" was considered helpful in significantly more participants who used the strategy in follow-up (72 out of 89, 80.9%) compared with baseline (55 out of 95, 57.9%; p = .008). Between visits, 81.2% looked at the brochure. Among participants, 53.1% found the brochure helpful, very helpful, or extremely helpful. CONCLUSIONS: A brochure that offered strategies to manage changes in taste helped participants cope with them. Further research should evaluate the brochure using randomized and multicenter trials.

Taste and Smell Disorders in Cancer Treatment: Results from an Integrative Rapid Systematic Review.

Taste and smell disorders (TSDs) are common side effects in patients undergoing cancer treatments. Knowing which treatments specifically cause them is crucial to improve patients' quality of life. This review looked at the oncological treatments that cause taste and smell alterations and their time of onset. We performed an integrative rapid review. The PubMed, PROSPERO, and Web of Science databases were searched in November 2022. The article screening and study selection were conducted independently by two reviewers. Data were analyzed narratively. Fourteen studies met the inclusion criteria and were included. A high heterogeneity was detected. Taste disorders ranged between 17 and 86%, while dysosmia ranged between 8 and 45%. Docetaxel, paclitaxel, nab-paclitaxel, capecitabine, cyclophosphamide, epirubicin, anthracyclines, and oral 5-FU analogues were found to be the drugs most frequently associated with TSDs. This review identifies the cancer treatments that mainly lead to taste and smell changes and provides evidence for wider studies, including those focusing on prevention. Further studies are warranted to make conclusive indication possible.

Lactoferrin supplementation for taste and smell abnormalities among patients receiving cancer chemotherapy.

PURPOSE: Taste and smell abnormalities (TSA) are common in patients receiving chemotherapy and may lead to altered nutritional intake, treatment withdrawal, and impaired quality of life. Lipid peroxidation in the oral cavity is one cause of TSA. Lactoferrin (LFN), an iron-binding salivary protein, reduces production of lipid oxidation byproducts and has been shown to reduce perception of unpleasant flavors. To assess the feasibility of LFN as a treatment for TSA, we conducted pilot investigations among patients with cancer who self-reported TSA following onset of chemotherapy. The primary objective was to assess change in subjective taste and smell perception from baseline to completion of 30 days of LFN supplementation. METHODS: Patients were treated with 750 mg LFN daily for 30 days and followed for an additional 30 days without LFN. TSA was measured via the taste and smell questionnaire (TSQ) including taste (score 0-10), smell (score 0-6), and composite scores (0-16) (0 = no TSA) at baseline, day 30, and day 60. RESULTS: A total of 26 patients enrolled; 19 remained on study at day 30 and 17 at day 60. Baseline mean TSQ scores were 6.5 (taste), 3.1 (smell), and 9.6 (composite). By day 30, mean composite TSQ score improved by 1.7 (p = 0.018); taste and smell improved by 0.6 (p = 0.062) and 1.1 (p = 0.042), respectively. From baseline to day 60, mean composite TSQ score improved by 3.8 (p < 0.0001); taste and smell improved by 1.9 (p = 0.001) and 1.8 (p = 0.003). CONCLUSIONS: Further evaluation of LFN is warranted to determine its value for improving self-reported TSA among patients receiving chemotherapy.

Chemotherapy-induced taste and smell changes influence food perception in cancer patients.

PURPOSE: Chemotherapy-induced taste and smell alterations may have a negative impact on the quality of life and nutritional status. A prominent issue when dealing with taste and smell alterations and their consequences on food behavior and well-being lies in the variation arising from individual differences in chemosensory perceptions. The main aim of this study was to examine the effect of individuals' variation in the severity of taste and smell alterations relative to the stage of chemotherapy on self-reported food behavior and food perception. METHODS: Eighty-nine cancer patients completed a questionnaire subdivided into two parts: a chemosensory part that allowed classification of patients in three groups ("no alterations," "moderate alterations," and "severe alterations") and a food behavior part. RESULTS: The results highlighted a negative impact of chemosensory alterations on food perception. Compared with patients without taste and smell alterations, patients with severe chemosensory alterations reported significantly more frequent food perception problems, including modification of the perceived taste of food, finding bad taste in all food, and being unable to perceive food taste. Whereas 72% of patients with severe alterations were in late stage, only 37% of patients were in late stage in the no alterations group, indicating an effect of the treatment stage on taste and smell alterations. CONCLUSION: Our results underlie the importance of providing specific attention to the severity of chemotherapy-induced taste and smell alterations and considering the individual differences among patients for a better nutritional management.

Chemotherapy alters subjective senses of taste and smell but not dietary patterns in Japanese lung cancer patients.

PURPOSE: To investigate how outpatient-based chemotherapy would alter the senses of taste and smell and affect daily dietary intake in patients with lung cancer. METHODS: The self-reported taste and smell alteration (TSA) in 35 Japanese patients with lung cancer as well as their patterns of dietary intake at home were tested using a questionnaire. RESULTS: The patients experienced considerable TSA, and smoking was shown to contribute to this alteration. Specifically, current or past smokers were more likely to experience subjective taste change during chemotherapy than never smokers were. Chemotherapy made steamed rice or sushi the most unfavorable food in the patients; on the other hand, Japanese-style noodles were the most preferred during chemotherapy. Nevertheless, the patients maintained their habit of consuming steamed rice at home at least once a day, suggesting the robustness of dietary habits despite the TSA caused by chemotherapy. CONCLUSIONS: Nutritional assessment as well as appropriate advice and intervention by dietitians is expected to improve the general conditions and quality of daily living in patients with cancer.

Oral adverse effects of drugs: Taste disorders.

OBJECTIVE: Oral healthcare professionals are frequently confronted with patients using drugs on a daily basis. These drugs can cause taste disorders as adverse effect. The literature that discusses drug-induced taste disorders is fragmented. This article aims to support oral healthcare professionals in their decision making whether a taste disorder can be due to use of drugs by providing a comprehensive overview of drugs with taste disorders as an adverse effect. MATERIALS AND METHODS: The national drug information database for Dutch pharmacists, based on scientific drug information, guidelines, and summaries of product characteristics, was analyzed for drug-induced taste disorders. "MedDRA classification" and "Anatomic Therapeutical Chemical codes" were used to categorize the results. RESULTS: Of the 1,645 drugs registered in the database, 282 (17%) were documented with "dysgeusia" and 61 (3.7%) with "hypogeusia." Drug-induced taste disorders are reported in all drug categories, but predominantly in "antineoplastic and immunomodulating agents," "antiinfectives for systemic use," and "nervous system." In ~45%, "dry mouth" coincided as adverse effect with taste disorders. CONCLUSION: Healthcare professionals are frequently confronted with drugs reported to cause taste disorders. This article provides an overview of these drugs to support clinicians in their awareness, diagnosis, and treatment of drug-induced taste disorders.

Drinking Ice-Cold Water Reduces the Severity of Anticancer Drug-Induced Taste Dysfunction in Mice.

Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans.

Clinical and Toxicological Profile of NBOMes: A Systematic Review.

BACKGROUND: NBOMes are a new class of potent hallucinogens widely present in illicit drugs. Little is known about this class of drugs, regarding its detection and clinical manifestations of intoxication. OBJECTIVE: This study aims to enhance care involving NBOMes by reviewing the literature on their clinical manifestations and laboratorydetection. METHODS: A systematic review was performed on the clinical manifestations and laboratory tests of NBOMEs ingestion. Embase, Pubmed, PsycINFO, and Cochrane databases were employed in this analysis. RESULTS: Forty-five articles met the inclusion criteria out of the 2814 nonduplicated studies on the theme. Seventy case reports of intoxication were found in the analyzed articles (64.3% were men and 11.4% were women, mean age of 22.5). The technique most employed for NBOMes identification was chromatography of blood, urine, and oral fluids. Moreover, the studies identified 13 chemical structures differentfrom the NBOMes on their toxicological analyses.According to these studies, most of these drugs were ingested orally-nasal use was the second preferred administration route, followed by intravenous administration. CONCLUSION: Better identification of the clinicalmanifestations and laboratory profile of NBOMes is crucial to the recognition of intoxication as well as to its effective treatment.

Adverse events in people taking macrolide antibiotics versus placebo for any indication.

BACKGROUND: Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated. Because adverse events are treatment-specific, rather than disease-specific, it is possible to increase the number of adverse events available for analysis by combining randomised controlled trials (RCTs) of the same treatment across different diseases. OBJECTIVES: To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Acute Respiratory Infections Group Specialised Register (2018, Issue 4); MEDLINE (Ovid, from 1946 to 8 May 2018); Embase (from 2010 to 8 May 2018); CINAHL (from 1981 to 8 May 2018); LILACS (from 1982 to 8 May 2018); and Web of Science (from 1955 to 8 May 2018). We searched clinical trial registries for current and completed trials (9 May 2018) and checked the reference lists of included studies and of previous Cochrane Reviews on macrolides. SELECTION CRITERIA: We included RCTs that compared a macrolide antibiotic to placebo for any indication. We included trials using any of the four most commonly used macrolide antibiotics: azithromycin, clarithromycin, erythromycin, or roxithromycin. Macrolides could be administered by any route. Concomitant medications were permitted provided they were equally available to both treatment and comparison groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and collected data. We assessed the risk of bias of all included studies and the quality of evidence for each outcome of interest. We analysed specific adverse events, deaths, and subsequent carriage of macrolide-resistant bacteria separately. The study participant was the unit of analysis for each adverse event. Any specific adverse events that occurred in 5% or more of any group were reported. We undertook a meta-analysis when three or more included studies reported a specific adverse event. MAIN RESULTS: We included 183 studies with a total of 252,886 participants (range 40 to 190,238). The indications for macrolide antibiotics varied greatly, with most studies using macrolides for the treatment or prevention of either acute respiratory tract infections, cardiovascular diseases, chronic respiratory diseases, gastrointestinal conditions, or urogynaecological problems. Most trials were conducted in secondary care settings. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin.Most studies (89%) reported some adverse events or at least stated that no adverse events were observed.Gastrointestinal adverse events were the most commonly reported type of adverse event. Compared to placebo, macrolides caused more diarrhoea (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.34 to 2.16; low-quality evidence); more abdominal pain (OR 1.66, 95% CI 1.22 to 2.26; low-quality evidence); and more nausea (OR 1.61, 95% CI 1.37 to 1.90; moderate-quality evidence). Vomiting (OR 1.27, 95% CI 1.04 to 1.56; moderate-quality evidence) and gastrointestinal disorders not otherwise specified (NOS) (OR 2.16, 95% CI 1.56 to 3.00; moderate-quality evidence) were also reported more often in participants taking macrolides compared to placebo.The number of additional people (absolute difference in risk) who experienced adverse events from macrolides was: gastrointestinal disorders NOS 85/1000; diarrhoea 72/1000; abdominal pain 62/1000; nausea 47/1000; and vomiting 23/1000.The number needed to treat for an additional harmful outcome (NNTH) ranged from 12 (95% CI 8 to 23) for gastrointestinal disorders NOS to 17 (9 to 47) for abdominal pain; 19 (12 to 33) for diarrhoea; 19 (13 to 30) for nausea; and 45 (22 to 295) for vomiting.There was no clear consistent difference in gastrointestinal adverse events between different types of macrolides or route of administration.Taste disturbances were reported more often by participants taking macrolide antibiotics, although there were wide confidence intervals and moderate heterogeneity (OR 4.95, 95% CI 1.64 to 14.93; I² = 46%; low-quality evidence).Compared with participants taking placebo, those taking macrolides experienced hearing loss more often, however only four studies reported this outcome (OR 1.30, 95% CI 1.00 to 1.70; I² = 0%; low-quality evidence).We did not find any evidence that macrolides caused more cardiac disorders (OR 0.87, 95% CI 0.54 to 1.40; very low-quality evidence); hepatobiliary disorders (OR 1.04, 95% CI 0.27 to 4.09; very low-quality evidence); or changes in liver enzymes (OR 1.56, 95% CI 0.73 to 3.37; very low-quality evidence) compared to placebo.We did not find any evidence that appetite loss, dizziness, headache, respiratory symptoms, blood infections, skin and soft tissue infections, itching, or rashes were reported more often by participants treated with macrolides compared to placebo.Macrolides caused less cough (OR 0.57, 95% CI 0.40 to 0.80; moderate-quality evidence) and fewer respiratory tract infections (OR 0.70, 95% CI 0.62 to 0.80; moderate-quality evidence) compared to placebo, probably because these are not adverse events, but rather characteristics of the indications for the antibiotics. Less fever (OR 0.73, 95% 0.54 to 1.00; moderate-quality evidence) was also reported by participants taking macrolides compared to placebo, although these findings were non-significant.There was no increase in mortality in participants taking macrolides compared with placebo (OR 0.96, 95% 0.87 to 1.06; I² = 11%; low-quality evidence).Only 24 studies (13%) provided useful data on macrolide-resistant bacteria. Macrolide-resistant bacteria were more commonly identified among participants immediately after exposure to the antibiotic. However, differences in resistance thereafter were inconsistent.Pharmaceutical companies supplied the trial medication or funding, or both, for 91 trials. AUTHORS' CONCLUSIONS: The macrolides as a group clearly increased rates of gastrointestinal adverse events. Most trials made at least some statement about adverse events, such as "none were observed". However, few trials clearly listed adverse events as outcomes, reported on the methods used for eliciting adverse events, or even detailed the numbers of people who experienced adverse events in both the intervention and placebo group. This was especially true for the adverse event of bacterial resistance.

Topical application of 5-fluorouracil 5 percent cream associated with severe neutropenia: discussion of a case and review of systemic reactions after topical treatment with 5-fluorouracil.

5-fluorouracil, a fluoropyrimidine antineoplastic drug, is used to topically treat actinic keratoses. Local skin reactions to the medication are common and anticipated. However, severe adverse events from topical 5-fluorouracil are rare and unexpected. A 69-year-old man with a lower lip actinic keratosis developed severe neutropenia on day 11 of topical 5-fluorouracil treatment - after 14 applications. After receiving a subcutaneous injection of filgrastim, his neutrophil count normalized. The PubMed database was used to search the following terms: agranulocytosis, cream, 5-fluorouracil, granulocytopenia, neutropenia, severe, systemic, topical, and toxicity. The papers, and relevant cited references, generated were reviewed. Systemic reactions to topical 5-fluorouracil included angioedema, melanonychia, neurologic conditions (such as acute cerebellar syndrome, headaches, and peripheral neuropathy exacerbation), taste alteration, and systemic toxicity requiring hospitalization (including severe neutropenia). One of the individuals (a man with severe neutropenia and other symptoms) also had a deficiency of dihydropyrimidine dehydrogenase, the enzyme that catalyzes the rate-limiting step in 5-fluorouracil metabolism. Evaluation for dihydropyrimidine dehydrogenase deficiency is not routinely performed in patients receiving systemic or topical 5-fluorouracil. Also, the incidence of potentially severe 5-fluorouracil-induced toxicity associated with topical application of the drug may be greater than documented.

Metallic Taste in Cancer Patients Treated with Systemic Therapy: A Questionnaire-based Study.

A metallic taste is reported by cancer patients as a side effect of systemic therapy. Despite the high prevalence, this taste alteration has received limited attention. The present study investigated: 1) the prevalence of metallic taste in cancer patients treated with systemic therapy; 2) possible predictors of metallic taste; and 3) characteristics of metallic taste. A heterogeneous population of 127 cancer patients, who had received systemic treatment in the past year or were still on treatment, completed a questionnaire developed for this study. Fifty-eight of 127 (46%) patients reported taste changes in the preceding week. Of these patients, 20 (34%) reported a metallic taste. Patients treated with chemotherapy, concomitant radiotherapy, as well as targeted therapy reported metallic taste. Women experienced metallic taste more often than men. Patients experiencing a metallic taste also reported more frequently that they were bothered by sour food and that everything tasted bitter. The experience of metallic taste was highly variable among patients. In conclusion, metallic taste is a frequently experienced taste alteration by cancer patients. Patients treated with chemotherapy, concomitant radiotherapy, and targeted therapy are all at risk for this taste alteration. However, not all patients reported this alteration as bothersome.

Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma.

Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1-2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy. IMPLICATIONS FOR PRACTICE: The hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life and treatment discontinuation. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to administration of HPIs are described, with the goal of enabling health care professionals to provide appropriate counseling and supportive care interventions to their patients.

Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats.

As one of the adverse effects of oxaliplatin, a key agent in colon cancer chemotherapy, a taste disorder is a severe issue in a clinical situation because it decreases the quality of life of patients. However, there is little information on the mechanism underlying the oxaliplatin-induced taste disorder. Here, we examined the molecular and behavioral characteristics of the oxaliplatin-induced taste disorder in rats. Oxaliplatin (4-16 mg/kg) was administered to Sprague-Dawley (SD) rats intraperitoneally for 2 d. Expression levels of mRNA and protein of taste receptors in circumvallate papillae (CP) were measured by real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry, respectively. Taste sensitivity was assessed by their behavioral change using a brief-access test. Morphological change of the taste buds in CP was evaluated by hematoxyline-eosin (HE) staining, and the number of taste cells in taste buds was counted by immunohistochemical analysis. Among taste receptors, the expression levels of mRNA and protein of T1R2, a sweet taste receptor subunit, were increased transiently in CP of oxaliplatin-administered rats on day 7. In a brief-access test, the lick ratio was decreased in oxaliplatin-administered rats on day 7 and the alteration was recovered to the control level on day 14. There was no detectable alteration in the morphology of taste buds, number of taste cells or plasma zinc level in oxaliplatin-administered rats. These results suggest that decreased sensitivity to sweet taste in oxaliplatin-administered rats is due, at least in part, to increased expression of T1R2, while these alterations are reversible.

[The Effectiveness of Polaprezinc Preparation for Taste Alteration in Cancer Chemotherapy].

Taste alteration is an adverse effect of cancer chemotherapy that can cause a decrease in the nutritional status owing to appetite suppression. In most cases, taste alteration is attributed to zinc deficiency, which is treated using zinc-containing formulations, such as polaprezinc. Polaprezinc has commonly been administered to protect against taste alteration during the course of cancer chemotherapy, but its efficacy has not been fully evaluated. In addition, the background characteristics of the patients who are likely to experience taste alteration have not been fully investigated. Therefore, the effectiveness of zinccontaining formulations in the prevention of taste alteration was investigated retrospectively in our hospital. The objective of this study was to evaluate the presence of taste alteration and the effectiveness of polaprezinc administration in 136 female breast cancer patients who underwent FEC100 therapy between April 2011 and September 2014. We also investigated the relevance of the patient background factors in the occurrence of taste alteration(age, height, weight, body surface area, and levels of hemoglobin, serum iron, albumin, and total protein). Of 58 patients with taste alteration, 20 received polaprezinc, with the following outcomes: taste alteration improved in 70.0% of the patients, no change was observed in 25.0%, and the condition worsened in 5.0%. In a multiple regression analysis, the body surface area and decreased hemoglobin level were found to be significant independent factors that influence the development of taste alteration(p=0.003 and p=0.021, respectively). These results indicate that for patients who receive high doses of anticancer agents according to their body surface area and likelihood of anemia, such as that due to iron deficiency, early administration of zinc-containing formulations is anticipated to prevent taste alteration.

Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands.

Drug-induced taste disturbance is a common adverse drug reaction often triggered by drug secretion into saliva. Very little is known regarding the molecular mechanisms underlying salivary gland transport of xenobiotics, and most drugs are assumed to enter saliva by passive diffusion. In this study, we demonstrate that salivary glands selectively and highly express OCT3 (organic cation transporter-3), a polyspecific drug transporter in the solute carrier 22 family. OCT3 protein is localized at both basolateral (blood-facing) and apical (saliva-facing) membranes of salivary gland acinar cells, suggesting a dual role of this transporter in mediating both epithelial uptake and efflux of organic cations in the secretory cells of salivary glands. Metformin, a widely used anti-diabetic drug known to induce taste disturbance, is transported by OCT3/Oct3 in vitro. In vivo, metformin was actively transported with a high level of accumulation in the salivary glands of wild-type mice. In contrast, active uptake and accumulation of metformin in salivary glands were abolished in Oct3(-/-) mice. Oct3(-/-) mice also showed altered metformin pharmacokinetics and reduced drug exposure in the heart. These results demonstrate that OCT3 is responsible for metformin accumulation and secretion in salivary glands. Our study uncovered a novel carrier-mediated pathway for drug entry into saliva and sheds new light on the molecular mechanisms underlying drug-induced taste disorders.

Electrogustometry and contact endoscopy findings in patients with head and neck malignancies treated with chemotherapy, radiotherapy, or radiochemotherapy.

This study aimed to investigate in parallel changes in gustatory function, changes in morphology of the fungiform papillae, as well as changes in the shape and density of the vessels of the tip of the tongue in patients treated with chemotherapy, radiotherapy, or radiochemotherapy. Twenty patients (7 females and 13 males; age range: 42-78 years) with head and neck malignancies (hypopharynx, larynx, oropharynx, and parotid) treated with radiochemotherapy (n = 8), chemotherapy (n = 8), or radiotherapy (n = 4) were prospectively studied. In all patients, electrogustometry and contact endoscopy were performed. Radiotherapy-treated patients exhibited higher electrogustometry thresholds and greater alterations in the morphology and vascularization of the fungiform papillae than the other two groups. Radiochemotherapy patients had less pronounced changes of the electrogustometry threshold and fungiform papillae structure compared with radiotherapy patients. Chemotherapy alone caused less severe change in both electrogustometry threshold and fungiform papillae structure than radiotherapy or radiochemotherapy. Radiotherapy alone caused greater disorders of taste-related anatomic parameters and electrogustometry thresholds compared with chemotherapy and combined radiochemotherapy.

New posology of potassium iodide for the treatment of cutaneous sporotrichosis: study of efficacy and safety in 102 patients.

BACKGROUND: The first therapeutic choice for the treatment of cutaneous sporotrichosis is oral itraconazole; however, the increase in cases of zoonotic transmission outbreak necessitates a search for effective and safe treatment alternatives. OBJECTIVE: To evaluate a new potassium iodide (KI) posology as an alternative for the treatment of limited cutaneous forms of sporotrichosis. METHODS: One hundred and two patients with sporotrichosis diagnosed by isolation of Sporothrix sp. were included and were divided into 2 groups that received different doses of KI: group A received the conventional dose, and group B received the reduced dose. The cure criteria were based on clinical and serological data. RESULTS: Seventy-nine patients (77.4%) reached clinical cure: 70.6% and 84.3% of groups A and B respectively. Sixteen patients (15.6%) were lost during follow-up, and seven changed drug therapy: five in group A and two in group B. The incidence of adverse events was similar for both groups (64.7%): predominantly metallic taste (44%), followed by mild gastrointestinal intolerance and acneiform eruption (10.7% each). No serious adverse events occurred, and there were no recurrences. Analysis of the results showed no statistically significant difference between groups (P = 0.9255). The improvement in serologic titres was significant in both treatment groups. CONCLUSION: Through statistical analysis, the usual posology was not shown to be superior to the one proposed in this study. Serology for sporotrichosis may be used as a valuable tool in the clinical monitoring of these patients.

Possible peripheral mechanism for taste disorder in rats administered S-1.

BACKGROUND: Taste disorders are frequently observed in cancer patients undergoing chemotherapy and are serious adverse events which impair the quality of life (QoL) of the cancer patient. Nevertheless, taste disorder mechanisms in cancer patients undergoing chemotherapy have not yet been fully elucidated. The aim of this study was to reveal taste disorder-related peripheral mechanisms using the two-bottle preference test (TBPT) and histological examination of tongues by hematoxylin-eosin staining and immunohistochemistry with protein-gene product 9.5. METHODS: In the TBPT, one bottle was filled with the 0.01 mM quinine hydrochloride (quinine), as a bitter compound, and the other was filled with water. Doses of 50 and 100 mg kg(-1) day(-1) S-1 (tegafur/gimeracil/oteracil potassium) are lethal to Wistar rats. Therefore, doses ranging from 2-20 mg kg(-1) day(-1) were administered to the rats for 3 weeks. The S-1 dose of 2 mg kg(-1) day(-1) corresponds to the clinical dose administered to cancer patients. The part of the tongue containing the circumvallate papillae was excised the following TBPT. RESULTS: The rate of increase in terms of the average preference rate for the quinine vs. all intake (quinine plus water) was significant from the initial S-1 period to the final one, compared with that in control rats, suggesting the possibility of a worsening sensation for the bitter taste. In S-1 rats, the area of taste nerve fibers were significantly decreased and the rate of degeneration of intra-tongue ganglionic nerve cells was significantly increased. These changes were significantly correlated with the rate of increase in average preference rate of the quinine. CONCLUSION: Neuropathy of the gustatory nerve at the periphery may be involved in taste disorders induced by an anticancer drug.