Drug-induced Tongue Disorders: A Comprehensive Literature Review.

BACKGROUND: Some drugs cause tongue disorders as adverse effects. Most of the druginduced tongue disorders are benign and will resolve after drug discontinuation. However, the changes in the color or appearance of the tongue may frighten patients and decrease compliance with drug therapy. OBJECTIVE: To review the literature to find all reports of drug-induced tongue disorders, their presentation, management, and outcome of patients Methods: The search was conducted in Google Scholar and PubMed using key words "ageusia," "burning tongue," "coated tongue," "drug-induced taste disturbances," "dysgeusia," "glossitis," "glossodynia," "hairy tongue," "hypogeusia," "stomatodynia," "stomatopyrosis," "swollen tongue" "tongue discoloration," "tongue irritation," "tongue numbness, "tongue oedema," and "tongue ulcer. All reports that were published from 1980 to 2022 in the English language were included in the study. Reports that were not in English language but had English abstracts with adequate data for extraction were also included. RESULTS: A total of 208 case reports and case series were included. The most reported drug classes were antineoplastic and immunomodulating agents and anti-infectives for systemic use, and the most common tongue disorders were tongue discoloration and black hairy tongue. Having good oral hygiene and discontinuing the offending drug could manage and resolve the problem. CONCLUSION: Drug-induced tongue disorders are not rare adverse drug reactions. They are benign in most cases, and withholding offending agents results in significant improvement or complete resolution of tongue lesions.

Synthesis and In Vitro Cytotoxicity of Novel Halogenated Dihydropyrano[3,2-b]Chromene Derivatives.

Lung and breast cancers are among the most common cancers. In the present work, initially, 6-bromo-; and 6-chloro-3-hydroxychromone compounds were prepared. In the next step, a series of 8-bromo-; and 8-chloro-dihyropyrano[3,2-b]chromene derivatives were synthesized by one-pot three component reaction of these two compounds, aromatic aldehydes, and ethyl cyanoacetate in the presence of triethylamine in EtOH at reflux conditions. The synthesized compounds were tested for their in vitro cytotoxic activity against A549 (lung cancer) and MCF-7 (breast cancer) cell lines. It was found that some compounds have high to moderate cytotoxicity, which makes them potential candidates for further studies. This study can be the basis for further studies to design and synthesis potent anticancer compounds and investigating their mechanism of action.

The Effect of Adjunctive Probiotics on Markers of Inflammation and Oxidative Stress in Bipolar Disorder: A Double-blind, Randomized, Controlled Trial.

BACKGROUND: Bipolar disorder (BD) is a chronic psychiatric illness. Concentrations of inflammatory cytokines are increased in BD. Supplementation with probiotics has shown promising effects in reducing inflammation and producing improvement in clinical symptoms in some psychiatric disorders. Therefore, we designed a clinical trial to assess the effects of adjunctive probiotics on markers of inflammation and oxidative stress in patients with BD. METHODS: In this 8-week, double-blind, randomized study, 38 patients suffering from BD type I were given a probiotic or placebo capsule each day. Serum levels of interleukin-6 (IL-6), as the primary outcome measure, and of interleukin-10 (IL-10), tumor necrosis factor-α, and malondialdehyde, as the secondary outcome measures, were obtained before and after the intervention. RESULTS: At the end of the study, the 2 groups showed no significant or clinically meaningful differences in the serum concentrations of IL-6 [Hedge g=0.02, 95% confidence interval (CI): -0.6; 0.64, P=0.936], tumor necrosis factor-α (Hedge g=-0.2, 95% CI: -0.82; 0.42, P=0.554), IL-10 (Hedge g=-0.072, 95% CI: -0.071; 0.56, P=0.827), and malondialdehyde (Hedge g=0.27, 95% CI: -0.37; 0.91, P=0.423). CONCLUSIONS: This study did not find any significant or conclusive effects of probiotics supplementation on markers of inflammation and oxidative stress in patients with BD. Further studies are needed before a conclusion can be drawn about the efficacy of probiotics in the management of BD.

Drug-induced stuttering: A comprehensive literature review.

Drug-induced stuttering (DIS) is a type of neurogenic stuttering (NS). Although DIS has not been reported as frequently as other cases of NS in the literature, it is not a negligible adverse drug reaction (ADR) which can significantly affect the quality of life if not treated. This literature review aims to evaluate the epidemiological and clinical characteristics of DIS and suggests some pathophysiological mechanisms for this ADR. Relevant English-language reports in Google Scholar, PubMed, Web of Science, and Scopus were identified and assessed without time restriction. Finally, a total of 62 reports were included. Twenty-seven drugs caused 86 episodes of stuttering in 82 cases. The most episodes of DIS were related to antipsychotic drugs (57%), mostly including clozapine, followed by central nervous system agents (11.6%) and anticonvulsant drugs (9.3%). The majority of the cases were male and between the ages of 31 and 40 years. Repetitions were the most frequent core manifestations of DIS. In 55.8% of the episodes of DIS, the offending drug was withdrawn to manage stuttering, which resulted in significant improvement or complete relief of stuttering in all cases. Based on the suggested pathophysiological mechanisms for developmental stuttering and neurotransmitters dysfunctions involved in speech dysfluency, it seems that the abnormalities of several neurotransmitters, especially dopamine and glutamate, in different circuits and areas of the brain, including cortico-basal ganglia-thalamocortical loop and white matter fiber tracts, may be engaged in the pathogenesis of DIS.

Isolating and sequencing vB_Kpn_3, a lytic bacteriophage against multidrug-resistant Klebsiella pneumoniae.

Aim: Phage therapy, as an effective and specific method in the treatment of multidrug-resistant (MDR) bacterial infections, has attracted the attention of many researchers. Methods and results: In this study, a double-stranded DNA phage with the ability of lysing some strains of MDR Klebsiella pneumoniae (vB_Kpn_3) was isolated from hospitals' wastewater and then characterized morphologically and genetically. Transmission electron microscopy and genetic analyses have revealed that vB_Kpn_3 is a member of Siphoviridae family. One-step growth curve also showed a burst time of 35 min and a burst size of 31 PFU/ml. The genome of the phage is composed of 112,080 bp with 41.33% G + C content carrying 186 open reading frames. Conclusion: vB_Kpn_3 is a broad host range phage that infects MDR K. pneumoniae and some other species of Enterobacteriaceae such as Escherichia coli and Salmonella typhi. In addition, no antibiotic resistance and toxin genes were detected in its genome.

Evaluation of Relationship between Sever Early Childhood Caries and Breast Milk`s Lactose among 12- to 24-month-old Children.

Statement of the Problem: Severe early childhood caries (S-ECC) is common among infants and toddlers. It has many problems and challenges for families as well as dentists in fields of prevention and treatment. Purpose: The study aimed to investigate the relationship between occurrence of S-ECC and level of lactose in breast milk, in infants aged 12 to 24 months. Materials and Method: This cross-sectional descriptive-analytical study was carried out from April to July 2020 on 30 children aged 12 to 24 months with or without S-ECC, who were sol-ely breastfed; their mothers answered questions about their breastfeeding habits. After the child's dental visit, the mother was asked to express 10 to 20ml of her milk as a sample and give it to the researchers. The samples were immediately kept at -4°C and then they were tested for lactose measurement. Finally, the test results were analyzed by SPSS 21 software using independent t-test. Results: The average amount of lactose in the breast milk of cases with S-ECC infant was 5.74g/100 ml and the average amount of lactose in the breast milk of cases without S-ECC infant was 4.64g/100 ml. There was no significant difference in lactose concentration between the two groups (p Value=0.64). The average number of breastfeeding times in cases with S-ECC infants was 7.87 per day while in the healthy cases this was 7.33 per day. There was no significant difference between the numbers of breastfeeding times per day in two groups. Conclusion: According to this study, the amount of lactose in breast milk of children with S-ECC was slightly higher than the amount of lactose in breast milk in children with healthy teeth.

Effects of probiotics on pentylenetetrazol-induced convulsions in mice.

OBJECTIVE: There are some reports of the effect of the gut microbiota on the central nervous system. The aim of this study was to find out the effect of probiotics on pentylenetetrazol (PTZ)-induced convulsions in mice. METHODS: The mice were pretreated with probiotic powder (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum) suspended in normal saline by intragastric gavage (IG-gavage) for 14 (group 1) or 28 (group 2) days prior to injection of PTZ (90 mg/kg, intraperitoneally). Diazepam (DZP, 1 mg/kg, intraperitoneally) was used as the reference drug. The latency and duration of induced convulsion, as well as mortality protection percentage were recorded 30 min after PTZ injection. For the next step, flumazenil (FLZ) was used to block the effect of DZP. RESULTS: Pretreatment with probiotics for 14 or 28 days had not a significant effect on the latency and duration of seizures induced by PTZ. Neither seizure nor mortality was observed in co-administration of probiotics with DZP. FLZ pretreatment decreased the DZP-induced seizure latency; however, FLZ could not have such an effect in probiotic and DZP group. CONCLUSION: Probiotics alone did not show anticonvulsant effects, but enhanced the anticonvulsant effect of DZP; this suggests the involvement of GABAergic system.

Anxiety, depression, and oral health: A population-based study in Southeast of Iran.

BACKGROUND: Depression and anxiety are two psychosocial illnesses that mostly are comorbid. The prevalence of these diseases is increasing worldwide. Both can affect general health also oral and dental health. The effects can be physiological and behavioral. Patients with these disorders are not willing to keep oral hygiene. The purpose of this study was to investigate the association between depression/anxiety and oral health indices in the 15-75-year-old population of Kerman. MATERIALS AND METHODS: This cross-sectional study recruited 5900 people aged 15-75 years through one-stage cluster sampling (Kerman coronary artery disease risk factors study, KERCADRS). Data were collected through beck questionnaires for anxiety and depression and clinical examinations. Oral health indices including decayed, missing, filled teeth, gingival index (GI), and community periodontal index (CPI) were also measured. Data were analyzed by SPSS 21 software. Chi-square, t-test and regression analysis were used to determine the relationship between the variables. P ≤0.05 was considered as the level of statistical significance. RESULTS: In the study, 1975 (33.6%) of patients showed moderate-to-severe anxiety and 3502 (59.5%) got the scores as depressed. There was a significant difference between GI and CPI indices of the normal and depressed group (P < 0.01), but the difference in the anxious and normal group was not statistically significant (P > 0.05). CONCLUSION: The results of the study showed a significant relationship between depression and oral health indices but not with anxiety. Therefore, the present study suggests that more attention should be paid to the oral health of people with a history of depression.

Effect of pretreatment with intracerebroventricular injection of minocycline on morphine-induced memory impairment in passive avoidance test: Role of P-CREB and c-Fos expression in the dorsal hippocampus and basolateral amygdala regions.

Minocycline as a member of the tetracycline family is a lipophilic broad-spectrum antibiotic, which can display some non-antibiotic properties such as antioxidant, antiapoptosis, neuroprotection and modulation of pharmacological traits of drugs of abuse (ie, reward, sensitization and/or analgesia). Thus, the aim of the present study was to investigate the effect of intracerebroventricular (ICV) injection of minocycline on morphine-induced memory impairment and motor function in male Wistar rats. The behavioural responses were measured by a passive avoidance test for evaluating memory, and in the open field for studying motor function. Furthermore, the expression of Phospho-cAMP response element-binding protein (P-CREB) and c-Fos were assessed using immunohistochemistry in the dorsal hippocampus and basolateral amygdala (BLA). Our results showed that morphine dose-dependently impairs memory consolidation, but not motor function. Maximum effect was achieved with morphine at dose of 5 mg/kg. Pretreatment with ICV injection of minocycline (50 µg/rat) prevented morphine-induced memory impairment, but there was no effect on motor function. The results of immunohistochemistry analysis demonstrated that morphine decreased expression of P-CREB positive cells compared to saline control group in the BLA, but not in the dorsal hippocampus. On the other hand, pretreatment of animals with ICV injection of minocycline increased the expression of P-CREB in both brain areas. Moreover, there was no significant change in the expression of c-Fos positive cells in above-mentioned regions. In summary, our results indicated that pretreatment with ICV injection of minocycline prevented morphine-induced memory impairment and increased P-CREB expression in the dorsal hippocampus and BLA, which may explain its memory improvement property.

Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies.

A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC50s less than 100 µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.

A minireview on the in vitro and in vivo experiments with anti-Escherichia coli O157:H7 phages as potential biocontrol and phage therapy agents.

Phage therapy is an old method of combating bacterial pathogens that has recently been taken into consideration due to the alarming spread of antibiotic resistance. Escherichia coli O157:H7 is a foodborne pathogen that causes hemorrhagic colitis and life-threatening Hemolytic Uremic Syndrome (HUS). There are several studies on isolation of specific phages against E. coli O157:H7 and more than 60 specific phages have been published so far. Although in vitro experiments have been successful in elimination or reduction of E. coli O157:H7numbers, in vivo experiments have not been as promising. This may be due to escape of bacteria to locations where phages have difficulties to enter or due to the adverse conditions in the gastrointestinal tract that affect phage viability and proliferation. To get around the latter obstacle, an alternative phage delivery method such as polymer microencapsulation should be tried. While the present time results are not very encouraging the work should be continued as more efficient phage treatment regimens might be found in future.