Adjunctive systemic antimicrobials in the treatment of chronic periodontitis: A systematic review and network meta-analysis.

The aim of this systematic review and network meta-analysis was to assess the efficacy of antimicrobials adjunctive to scaling and root planing (SRP) in the treatment of chronic periodontitis. The study was conducted according to the PRISMA statement. The protocol (CRD42020178621) was registered on the International Prospective Register of Systematic Reviews (PROSPERO). The MEDLINE, EMBASE, and CENTRAL databases were searched up to March 2020; furthermore, a manual search of relevant periodontal journals was conducted. Mean differences (MD) and standard deviations were calculated for clinical attachment level (CAL) gain and probing depth (PD) reduction at 6 and 12 months. A network meta-analysis was performed to assess direct and indirect comparisons and to establish a ranking of treatments. A total of 21 randomized clinical trials (RCTs) were included in the systematic review. Network meta-analysis showed that SRP + amoxicillin (AMX) + metronidazole (MTZ), as compared to SRP, reached the highest PD reduction at 6 [MD = 0.47; 95% CI (0.3; 0.64)] and 12 months [MD = 0.51; 95% CI (0.25; 0.78)], and CAL gain at 6 [MD = 0.54; 95% CI (0.27; 0.8)] and 12 months [MD = 0.37; 95% CI (0.05; 0.69)]. Network meta-analysis indicated that AMX + MTZ adjunctive to SRP provided the best improvement in clinical parameters, followed by SRP + MTZ.

The effects of ULF-TENS stimulation on gnathology: the state of the art.

AIMS: The aim of this study was to evaluate the state of the art in the current literature regarding the effect of ultra low frequency-transcutaneous electrical nerve stimulation (ULF-TENS) on patients with temporomandibular disorders (TMD). METHODOLOGY: The authors reviewed the literature through a thorough manual and electronic research on PubMed database (using the Medical Subject Headings thesaurus) and subsequent analysis of all the found papers regarding the effect of TENS on TMD patients. No randomized controlled trials on the investigated topic were found. Only eight papers regarding controlled clinical trials (CCT) were selected according to the search strategy selection criteria. RESULTS: According to the available literature and the authors' experience, ULF-TENS seems to be a valid support in the management of TMD patients, but also a 'provocative' tool, so its application should always be monitored by electromyographic and electrognathographic analysis (before and after TENS). CONCLUSIONS: Further clinical studies (mainly randomized controlled trials) on ULF-TENS application in neuromuscular gnathology are needed.

Does orthodontic treatment provide a real functional improvement? a case control study.

BACKGROUND: Electromyographic analysis of the masticatory muscles provides useful data on the behavior of these muscles during stomatognathic system functioning and allows a functional assessment of orthodontic treatments. This study was undertaken to verify if achieving an Angle Class I bite through orthodontic treatment can lead to neuromuscular balance. METHODS: This study enrolled 30 patients (20 females, 10 males, mean age: 15.78 years) with an Angle Class II, division 1 malocclusion that was orthodontically treated. A group of 30 subjects (19 females, 11 males; mean age: 16.15 years), randomly selected among subjects with an Angle Class II, division 1 malocclusion that had not been orthodontically treated served as the Control group. Both groups were subjected to electromyography to study their neuromuscular characteristics. The Shapiro-Wilk's test revealed a non normal distribution, therefore we used a Friedman two way ANOVA by ranks test to compare differences of surface electromyography values between treated and untreated subjects at closed and open eyes condition. RESULTS: A statistically significant interaction between orthodontic treatment and open eyes conditions was detected for anterior temporal muscles. A significant imbalance of the anterior temporal muscles, which is indicative of an asymmetric electromyographic pattern, was also found. CONCLUSIONS: The present data indicate that achieving a correct occlusal target does not necessarily correspond to a neuromuscular balance.

Effect of ill-fitting dentures on the swallowing duration in patients using polygraphy.

BACKGROUND: Surface electromyography (SEMG) has been widely used in the recent years to study swallowing physiology, offering a valid and reliable tool for identifying normal swallowing. The goal of our study was to assess the contribution of denture fitness in the age-related increase of swallowing duration. METHODS: Twenty denture wearers and 20 dentate individuals were analysed using SEMG and a computerised kinesiography of mandibular movement. Three spontaneous saliva swallowings were recorded for each patient with both their old and new prostheses. Three spontaneous saliva swallowings were recorded for each dentate person in two different recording sessions. RESULTS: Old prosthesis mean swallowing time was 1.84 (SD ± 0.85) seconds while the new well-fitting prostheses needed a 1.28 (SD ± 0.55) (p = 0.0009) swallowing time. The difference in swallowing time was significant (p = 0.01) between dentate subjects and individuals wearing an old prosthesis. No significant difference was found between dentate subjects and the same prosthesis wearers when a new well-fitting prosthesis was worn. CONCLUSION: Data presented in this work suggest that part of the increased duration of swallowing showed by elderly and healthy people is because of incorrect an dental prosthesis. Prolongation of swallowing duration in the elderly population could be reconsidered in the light of the quality of dental device worn by the aged population.

Surface electromyography pattern of human swallowing.

BACKGROUND: The physiology of swallowing is characterized by a complex and coordinated activation of many stomatognathic, pharyngeal, and laryngeal muscles. Kinetics and electromyographic studies have widely investigated the pharyngeal and laryngeal pattern of deglutition in order to point out the differences between normal and dysphagic people. In the dental field, muscular activation during swallowing is believed to be the cause of malocclusion.Despite the clinical importance given to spontaneous swallowing, few physiologic works have studied stomatognathic muscular activation and mandibular movement during spontaneous saliva swallowing.The aim of our study was to investigate the activity patterns of the mandibular elevator muscles (masseter and anterior temporalis muscles), the submental muscles, and the neck muscles (sternocleidomastoid muscles) in healthy people during spontaneous swallowing of saliva and to relate the muscular activities to mandibular movement. METHODS: The spontaneous swallowing of saliva of 111 healthy individuals was analyzed using surface electromyography (SEMG) and a computerized kinesiography of mandibular movement. RESULTS: Fifty-seven of 111 patients swallowed without occlusal contact (SNOC) and 54 individuals had occlusal contact (SOC). The sternocleidomastoid muscles showed a slight, but constant activation during swallowing. The SEMG of the submental and sternocleidomastoid muscles showed no differences between the two groups. The SEMG of the anterior temporalis and masseter muscles showed significant differences (p < 0.0001). The duration of swallowing was significantly higher in the SNOC subjects. Gender and age were not related to electromyographic activation. Healthy SOC and SNOC behaved in different ways. CONCLUSION: The data suggest that there is not a single "normal" or "typical" pattern for spontaneous saliva swallowing. The polygraph seemed a valuable, simple, non-invasive and reliable tool to study the physiology of swallowing.

Effects of intervertebral disc disorders of low back on the mandibular kinematic: kinesiographic study.

BACKGROUND: Intervertebral disc disorders are one of the most common causes of low back pain. Neuromuscular dysfunction frequently is present in patients with lumbar disc herniation.When considering joint dysfunction, it is important to remember that the spine functions as a unit. Dysfunction on one level can trigger compensatory changes in other spinal levels or in other areas of the musculoskeleton. Findings demonstrated the relationship between stomatognathic and postural systems justifying the hypothesis that muscular-skeletal impairment in one system could affect the other one. However, evidence that a lumbar intervertebral disc herniation could influence the mandibular kinematics is still lacking. Aim of this study was to analyse the effects that intervertebral disc herniation of low back could have on the mandibular kinematics. FINDINGS: Kinesiographic evaluations of the mandibular dynamics of 23 adult patients suffering L4/L5 and L5/S1 lumbosacral disc hernation were compared with a non pathological control group. A statistically significant difference of maximal mouth opening (p < .05) and of maximal mouth opening velocity (p < .03) was found comparing the study patients with the control subjects. CONCLUSION: Lumbosacral disc herniation appears to be associated with changes in the activity of mandibular kinematics both in rate and quality of movement. The study suggests the existence of connections between masticatory system and lumbar disk herniation.

Optimization of hydroxybenzothiazoles as novel potent and selective inhibitors of 17ß-HSD1.

17ß-HSD1 is a novel target for the treatment of estrogen-dependent diseases, as it catalyzes intracellular estradiol formation. Starting from two recently described compounds, highly active and selective inhibitors were developed. Benzoyl 6 and benzamide 17 are the most selective compounds toward 17ß-HSD2 described so far. They also showed a promising profile regarding activity in T47-D cells, selectivity toward ERα and ERß, inhibition of hepatic CYP enzymes, metabolic stability, and inhibition of marmoset 17ß-HSD1 and 17ß-HSD2.

Hydroxybenzothiazoles as new nonsteroidal inhibitors of 17ß-hydroxysteroid dehydrogenase type 1 (17ß-HSD1).

17ß-estradiol (E2), the most potent estrogen in humans, known to be involved in the development and progession of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17ß-HSD1, which catalyses the reduction of the weak estrogen estrone (E1) to E2, is often overexpressed in breast cancer and endometriotic tissues. An inhibition of 17ß-HSD1 could selectively reduce the local E2-level thus allowing for a novel, targeted approach in the treatment of EDD. Continuing our search for new nonsteroidal 17ß-HSD1 inhibitors, a novel pharmacophore model was derived from crystallographic data and used for the virtual screening of a small library of compounds. Subsequent experimental verification of the virtual hits led to the identification of the moderately active compound 5. Rigidification and further structure modifications resulted in the discovery of a novel class of 17ß-HSD1 inhibitors bearing a benzothiazole-scaffold linked to a phenyl ring via keto- or amide-bridge. Their putative binding modes were investigated by correlating their biological data with features of the pharmacophore model. The most active keto-derivative 6 shows IC50-values in the nanomolar range for the transformation of E1 to E2 by 17ß-HSD1, reasonable selectivity against 17ß-HSD2 but pronounced affinity to the estrogen receptors (ERs). On the other hand, the best amide-derivative 21 shows only medium 17ß-HSD1 inhibitory activity at the target enzyme as well as fair selectivity against 17ß-HSD2 and ERs. The compounds 6 and 21 can be regarded as first benzothiazole-type 17ß-HSD1 inhibitors for the development of potential therapeutics.

17ß-Hydroxysteroid dehydrogenases (17ß-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development.

17ß-Hydroxysteroid dehydrogenases (17ß-HSDs) are oxidoreductases, which play a key role in estrogen and androgen steroid metabolism by catalyzing final steps of the steroid biosynthesis. Up to now, 14 different subtypes have been identified in mammals, which catalyze NAD(P)H or NAD(P)(+) dependent reductions/oxidations at the 17-position of the steroid. Depending on their reductive or oxidative activities, they modulate the intracellular concentration of inactive and active steroids. As the genomic mechanism of steroid action involves binding to a steroid nuclear receptor, 17ß-HSDs act like pre-receptor molecular switches. 17ß-HSDs are thus key enzymes implicated in the different functions of the reproductive tissues in both males and females. The crucial role of estrogens and androgens in the genesis and development of hormone dependent diseases is well recognized. Considering the pivotal role of 17ß-HSDs in steroid hormone modulation and their substrate specificity, these proteins are promising therapeutic targets for diseases like breast cancer, endometriosis, osteoporosis, and prostate cancer. The selective inhibition of the concerned enzymes might provide an effective treatment and a good alternative to the existing endocrine therapies. Herein, we give an overview of functional and structural aspects for the different 17ß-HSDs. We focus on steroidal and non-steroidal inhibitors recently published for each subtype and report on existing animal models for the different 17ß-HSDs and the respective diseases. Article from the Special issue on Targeted Inhibitors.

New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) inhibitory activity and selectivity.

17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is responsible for the catalytic reduction of weakly active E1 to highly potent E2. E2 stimulates the proliferation of hormone-dependent diseases via activation of the estrogen receptor alpha (ERalpha). Because of the overexpression of 17beta-HSD1 in mammary tumors, this enzyme should be an attractive target for the treatment of estrogen-dependent pathologies. Recently, we have reported on a series of potent 17beta-HSD1 inhibitors: bis(hydroxyphenyl) azoles, thiophenes, and benzenes. In this paper, different substituents are introduced into the core structure and the biological properties of the corresponding inhibitors are evaluated. Computational methods and analysis of different X-rays of 17beta-HSD1 lead to identification of two different binding modes for these inhibitors. The fluorine compound 23 exhibits an IC(50) of 8 nM and is the most potent nonsteroidal inhibitor described so far. It also shows a high selectivity (17beta-HSD2, ERalpha) and excellent pharmacokinetic properties after peroral application to rats.