Tonsillolithiasis and orofacial pain

Tonsilloliths are rare calcified structures that usually result from chronic inflammation of the tonsils. Concretions show differences in size, shape and colour. They are usually asymptomatic but can be associated with halitosis, foreign body sensation, dysphagia and odynophagia, otalgia, and neck pain. A patient was referred because panoramic radiography performed by a general dentist revealed radiopaque shadows over the ascending rami of the mandible, located bilaterally: a solitary structure on the higher portion of the right side and two small structures on the left side. Paroxysmal attacks of orofacial pain and symptoms such as dysphagia and swallowing pain on the left side distributed within the tonsillar fossa and pharynx and the angle of the lower jaw were present. The computed tomography images revealed bilateral tonsilloliths. Clinically, there was no sign of inflammation, and the patient's past history revealed an approximately 2-year history of dysphagia, swallowing pain and left-sided neck pain. At the request of the patient, no surgical intervention was carried out. Glossopharyngeal neuralgia is a rare entity, and the aim of this report was to indicate the importance of tonsilloliths as a cause of orofacial pain.     

Breakthroughs in the genetics of orofacial clefting

Nonsyndromic orofacial clefts have a multifactorial etiology, involving both genetic and environmental factors. Although linkage and candidate gene studies have attempted to elucidate the underlying genetic architecture, only the interferon regulatory factor 6 (IRF6) gene has been identified as causative. The recent introduction of high-throughput genotyping technologies has enabled researchers to perform genome-wide association studies (GWAS). Four GWAS of nonsyndromic cleft lip with or without cleft palate have been conducted, and these have identified five new chromosomal loci. One locus, located in an intergenic region of chromosome 8q24, has been implicated in all GWAS and constitutes a major susceptibility locus. This review describes the latest genetic findings for nonsyndromic orofacial clefts and discusses their biological and functional implications.     

Real-time analysis of orofacial movements using electromagnetic articulography

A real-time version of electromagnetic articulography is presented, which permits the recording of five positions of the articulators in the oro-facial system. Movements can be shown online on PC screen. Owing to its biological safety and ease of handling, the system is especially suitable for clinical applications.     

The role of nitric oxide in orofacial pain

Nitric oxide (NO) is a free radical gas that has been shown to be produced by nitric oxide synthase (NOS) in different cell types and recognized to act as a neurotransmitter or neuromodulator in the nervous system. NOS isoforms are expressed and/or can be induced in the related structures of trigeminal nerve system, in which the regulation of NOS biosynthesis at different levels of gene expression may allow for a fine control of NO production. Several lines of evidence suggest that NO may play a role through multiple mechanisms in orofacial pain processing. This report will review the latest evidence for the role of NO involved in orofacial pain and the potential cellular mechanisms are also discussed.     

Reversal of haloperidol-induced orofacial dyskinesia and neuroinflammation by isoflavones

Molecular Biology Reports - Schizophrenia is a mental illness and its pharmacological treatment consists in the administration of antipsychotics like haloperidol. However, haloperidol often causes...     

Thymidylate synthase polymorphisms and risks of human orofacial clefts

OBJECTIVE: Underlying mechanisms are unknown by which folic acid use in early pregnancy may reduce risks of orofacial clefts. Thymidylate synthase (TYMS) is a folate‐dependent enzyme that catalyzes reductive methylation of deoxyuridylate to thymidylate, thereby playing a central role in DNA synthesis and repair. We investigated two TYMS functional variants (a 28‐bp tandem repeat in the promoter enhancer region of the 5′‐UTR; and TYMS 1494del6 (rs16430): a 6‐bp deletion in the 3′‐UTR) for their risk of cleft palate (CP) and of cleft lip with/without CP (CLP). We investigated effect measure modification between these variants and maternal folate intake for cleft risk. DESIGN: This case‐control study included deliveries from July 1999 to June 2003 from select areas of California. Case groups included CLP or CP alone. Nonmalformed, liveborn controls were randomly selected. Maternal interviews provided information on vitamin use and dietary folate intake. DNA was derived from newborn bloodspots. RESULTS: Data were available for 304 CLP cases, 123 CP cases, and 581 controls. 1496del6 variants did not appear to influence risk of CP or CLP. Homozygosity for the 28‐bp VNTR variant influenced CP risk (odds ratios, OR = 1.8, 95% confidence interval, 1.1–3.1), particularly among Hispanic infants, OR 2.1 (1.0–4.6). Effect measure modification was observed between the 28‐bp VNTR and combined folate intake for CP with an OR of 10.0 (1.6–60.9). CONCLUSION: Although these findings are consistent with biological mechanisms, they were based on relatively small sample sizes and may represent false‐positive discoveries. Replication is warranted in other populations. Birth Defects Research (Part A) 97:95–100, 2013. © 2013 Wiley Periodicals, Inc.     

Antinociceptive activity of atranorin in mice orofacial nociception tests

Physicochemical characterization and antinociceptive and anti-inflammatory activities of atranorin (AT) extracted from Cladina kalbii Ahti in formalin- and capsaicin-induced orofacial pain and anti-inflammatory tests in rodents were studied. Physicochemical characterization showed that AT has the general formula C19H18O8. Male Swiss mice were pretreated with AT (100, 200, and 400 mg/kg, i.p.), morphine (3 mg/kg, i.p.), or vehicle (0.9% saline with two drops of 0.2% Tween 80) before formalin (20 microl, 2%) or capsaicin (20 microl, 2.5 microg) were injected into the right vibrissa. Our results showed that i.p. treatment with AT displayed marked inhibitory effects in different orofacial pain tests in mice. AT (400 mg/kg, i.p.) was effective in reducing the nociceptive face-rubbing behavioural response in both phases of the formalin test, which was also naloxone-sensitive. Additionally, AT produced a significant antinociceptive effect at all doses in the capsaicin test. Such results were unlikely to be provoked by motor abnormality, since AT-treated mice exhibited no performance alteration on the rota rod apparatus. AT exhibited significant anti-inflammatory activity in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced hind paw edema in rats. Additionally, AT exhibited a dose-dependent antioxidant activity in vitro, as assessed by total radical-trapping antioxidant parameter and total antioxidant reactivity assays. All these findings suggest that AT might represent an important tool for the management of orofacial pain and/or inflammatory disorders.     

Developmental microRNA expression profiling of murine embryonic orofacial tissue

BACKGROUND: Orofacial development is a multifaceted process involving precise, spatio‐temporal expression of a panoply of genes. MicroRNAs (miRNAs), the largest family of noncoding RNAs involved in gene silencing, represent critical regulators of cell and tissue differentiation. MicroRNA gene expression profiling is an effective means of acquiring novel and valuable information regarding the expression and regulation of genes, under the control of miRNA, involved in mammalian orofacial development. METHODS: To identify differentially expressed miRNAs during mammalian orofacial ontogenesis, miRNA expression profiles from gestation day (GD) ‐12, ‐13 and ‐14 murine orofacial tissue were compared utilizing miRXplore microarrays from Miltenyi Biotech. Quantitative real‐time PCR was utilized for validation of gene expression changes. Cluster analysis of the microarray data was conducted with the clValid R package and the UPGMA clustering method. Functional relationships between selected miRNAs were investigated using Ingenuity Pathway Analysis. RESULTS: Expression of over 26% of the 588 murine miRNA genes examined was detected in murine orofacial tissues from GD‐12–GD‐14. Among these expressed genes, several clusters were seen to be developmentally regulated. Differential expression of miRNAs within such clusters wereshown to target genes encoding proteins involved in cell proliferation, cell adhesion, differentiation, apoptosis and epithelial‐mesenchymal transformation, all processes critical for normal orofacial development. CONCLUSIONS: Using miRNA microarray technology, unique gene expression signatures of hundreds of miRNAs in embryonic orofacial tissue were defined. Gene targeting and functional analysis revealed that the expression of numerous protein‐encoding genes, crucial to normal orofacial ontogeny, may be regulated by specific miRNAs. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.     

Corticosteroid use during pregnancy and risk of orofacial clefts

Background

The association between the risk of orofacial clefts in infants and the use of corticosteroids during pregnancy is unclear from the available evidence. We conducted a nationwide cohort study of all live births in Denmark over a 12-year period.

Methods

We collected data on all live births in Denmark from Jan. 1, 1996, to Sept. 30, 2008. We included live births for which information was available from nationwide health registries on the use of corticosteroids during pregnancy, the diagnosis of an orofacial cleft and possible confounders.

Results

There were 832 636 live births during the study period. Exposure to corticosteroids during the first trimester occurred in 51 973 of the pregnancies. A total of 1232 isolated orofacial clefts (i.e., cleft lip, cleft palate, or cleft lip and cleft palate) were diagnosed within the first year of life, including 84 instances in which the infant had been exposed to corticosteroids during the first trimester of pregnancy. We did not identify any statistically significant increased risk of orofacial clefts associated with the use of corticosteroids: cleft lip with or without cleft palate, prevalence odds ratio (OR) 1.05 (95% confidence interval [CI] 0.80–1.38]; cleft palate alone, prevalence OR 1.23 (95% CI 0.83–1.82). Odds ratios for risk of orofacial clefts by method of delivery (i.e., oral, inhalant, nasal spray, or dermatologic and other topicals) were consistent with the overall results of the study and did not display significant heterogeneity, although the OR for cleft lip with or without cleft palate associated with the use of dermatologic corticosteroids was 1.45 (95% CI 1.03–2.05).

Interpretation

Our results add to the safety information on a class of drugs commonly used during pregnancy. Our study did not show an increased risk of orofacial clefts with the use of corticosteroids during pregnancy. Indepth investigation of the pattern of association between orofacial clefts and the use of dermatologic corticosteroids during pregnancy indicated that this result did not signify a causal connection and likely arose from multiple statistical comparisons.The anti-inflammatory and immuno-suppressive properties of corticosteroids in pharmacotherapeutic doses has a wide range of clinical uses, such as for the treatment of asthma, atopic dermatitis and other allergic conditions, autoimmune diseases and cancer. However, caution is warranted for the use of corticosteroid medications during pregnancy. Corticosteroid use during pregnancy has been associated with orofacial clefts in animals, and similar risks in humans are suspected.^1,2 The available epidemiologic evidence favours an association, but many of the studies that have been done have been limited by recall bias and a lack of statistical power. The association between risk of orofacial clefts and the use of corticosteroids during pregnancy remains unclear.^3–10We conducted a nationwide cohort study in Denmark with independent and prospective determination of corticosteroid use during pregnancy and the diagnosis of orofacial clefts. Our study comprised all live births from January 1996 to September 2008.     

Maternal diseases and isolated orofacial clefts in Hungary

BACKGROUND: Isolated orofacial clefts (OFCs) are likely to be caused by gene-environment interaction; therefore, the objective of the current study was to evaluate the possible association between all maternal diseases during pregnancy and isolated cleft lip with or without cleft palate (CL+/-CP) and posterior cleft palate (PCP) in the offspring. METHODS: The database of the large population-based Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996, was evaluated. The database includes 1374 cases with isolated CL+/- CP and 601 with PCP, plus 38,151 matched population controls (without defects) and 20,868 patient controls with other defects. Data collection was based on prospective medical records, retrospective maternal data via a self-reported questionnaire, and home visits of nonresponding families. RESULTS: An increased risk for isolated CL+/- CP was found for children born to mothers with influenza, common cold, orofacial herpes, and gastroenteritis during pregnancy. Risk for isolated PCP was increased in children of mothers with influenza, sinusitis, and bronchitis. Among chronic maternal diseases, epilepsy and angina pectoris showed a higher prevalence in the mothers of children born with isolated OFCs (cases). CONCLUSIONS: Some maternal diseases are risk factors for the pathogenesis of isolated OFCs. It is worth considering the prevention of possible harmful effects of influenza by vaccination during the expected epidemic period.     

Maternal multivitamin use and orofacial clefts in offspring

BACKGROUND: Cleft lip with or without cleft palate (CLP) and cleft palate alone (CP) affect approximately 1 in 1000 infants and 1 in 2,500 infants, respectively. Studies of the relation between orofacial clefts and multivitamins or folic acid have been inconsistent. METHODS: We used data from a population-based case-control study involving 309 nonsyndromic cleft-affected births (222 with CLP, 87 with CP) and 3,029 control births from 1968 to 1980 to evaluate the relation between regular multivitamin use and the birth prevalence of orofacial clefts. RESULTS: We found a 48% risk reduction for CLP (odds ratio = 0.52, 95% confidence interval = 0.34-0.80) among mothers who used multivitamins during the periconceptional period or who started multivitamin use during the first postconceptional month, after controlling for several covariates. The risk reduction for CP was less than those for CLP (odds ratio = 0.81, 95% confidence interval = 0.44-1.52); however, a small number of CP cases limited interpretation. No risk reductions for CLP or CP were found for women who began multivitamin use in the second or third month after conception. CONCLUSIONS: The magnitude of the risk reduction in our study is comparable to those of other recent studies; our study does not support the contention that only large dosages of folic acid are needed to prevent orofacial clefts. More studies are needed to test the effects of multivitamins and varying dosages of folic acid on the recurrence and/or occurrence of orofacial clefts to provide information needed to determine possible prevention strategies. Published 2001 Wiley-Liss, Inc.     

Impaired orofacial motor functions on chronic temporomandibular disorders

Because temporomandibular disorders (TMDs) rehabilitation continues to be a challenge, a more comprehensive picture of the orofacial functions in patients with chronic pain is required. This study assessed the orofacial functions, including surface electromyography (EMG) of dynamic rhythmic activities, in patients with moderate-severe signs and symptoms of chronic TMD. It was hypothesized that orofacial motor control differs between patients with moderate-severe chronic TMD and healthy subjects. Seventy-six subjects (46 with TMD and 30 control) answered questionnaires of severity of TMD and chewing difficulties. Orofacial functions and EMG during chewing were assessed.Standardized EMG indices were obtained by quantitative analysis of the differential EMG signals of the paired masseter and temporal muscles, and used to describe muscular action during chewing.TMD patients showed significant greater difficulty in chewing; worse orofacial scores; longer time for free mastication; a less accurate recruitment of the muscles on the working and balancing sides, reduced symmetrical mastication index (SMI) and increased standardized activity during EMG test than healthy subjects. SMI, TMD severity and orofacial myofunctional scores were correlated (P < 0.01). Impaired orofacial functions and increased activity of the muscles of balancing sides during unilateral chewing characterized the altered orofacial motor control in patients with moderate-severe chronic TMD. Implications for rehabilitation are discussed.     

Maternal caffeine intake during pregnancy and orofacial clefts

BACKGROUND: Moderate caffeine intake during pregnancy is common, but little is known about its potential association with birth defects. METHODS: The National Birth Defects Prevention Study is a population‐based, case‐control study of major birth defects, excluding infants with single‐gene disorders and chromosomal abnormalities. This analysis includes infants with cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), excluding infants whose cleft was secondary to holoprosencephaly or amniotic band sequence. Mothers reported dietary caffeine intake from coffee, tea, sodas, and chocolate in the year before pregnancy and reported intake of medications containing caffeine during pregnancy. We assessed the association between dietary caffeine intake, frequency of consuming each type of caffeinated beverage, medications containing caffeine, and CL/P or CPO among infants born from October 1997 through December 2004. RESULTS: This analysis included 1531 infants with CL/P, 813 infants with CPO, and 5711 infants with no major birth defects (controls). Examining dietary sources among control mothers, 11% reported consuming at least 300 mg of caffeine per day and 17% reported consuming less than 10 mg of caffeine per day; high consumption (≥3 servings per day) was reported by 8% (coffee), 4% (tea), and 15% (sodas); medications containing at least 100 mg caffeine/dose were reported by less than 1%. Although some effect estimates were elevated for moderate caffeine intake from all beverages, estimates were closer to the null for high caffeine levels. Isolated CL/P was associated with use of medications containing at least 100 mg of caffeine per dose. CONCLUSIONS: Our data do not suggest an association between maternal dietary caffeine intake and orofacial clefts, but caffeine‐containing medications merit further study. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.