Spontaneous regeneration of bone following mandibular ramus bone harvesting: a CBCT analysis.

The aim of this study was to evaluate healing at the donor site following autogenous block graft harvesting from the mandibular ramus. In this retrospective study, cone beam computed tomography images taken at different time-points were examined, and the volumes of preoperative and postoperative regions of interest were calculated in the software. Images were classified into four groups: 0-3 months, 4-6 months, 7-12 months, and >12 months post-surgery. To characterize the healing process over time, statistical analyses were conducted for both the 70% and 80% healing thresholds. Nearly half (n = 15, 47%) of the 32 patients included in this study achieved 70% bone healing within 4-12 months post-surgery. At the end of the 28-month period covered by this study, 21 patients (66%) had achieved 70% bone healing. The median time to achieve 70% healing was 9 months, while the median time to achieve 80% healing was 28 months. The findings of this study validate the feasibility of reutilizing the mandibular ramus area for additional bone augmentation when other intraoral sites are unavailable.

Piezosurgery versus conventional rotary surgery for impacted third molars: A randomised, split-mouth, clinical pilot trial.

BACKGROUND: Few studies have compared the effects of piezosurgery and conventional rotary surgery for impacted wisdom teeth on the quality of life. Among these studies, the inclusion parameters and evaluation methods have varied. MATERIAL AND METHODS: This study aimed to compare the effects of piezosurgery and conventional rotary instruments on the quality of life using a standardised method. Patients with bilateral and symmetric mandibular impacted wisdom teeth were included based on the Winter and Pell-Gregory scale and Yuasa difficulty index criteria. The primary objective was to assess the effects of the methods on the quality of life using the Oral Health Impact Profile-14 questionnaire. Secondary objectives included comparisons of swelling, trismus, pain, and total operative times. The study was conducted between October 2021 and March 2022. The clinical trial protocol was recorded in the United States National Library of Medicine clinical trial registry (NCT05545553). RESULTS: We enrolled 20 patients (40 wisdom teeth) and found that the removal of impacted teeth using the piezosurgery method positively affected the quality of life and considerably improved swelling, trismus, and pain scores. However, piezosurgery may affect postoperative morbidities such as increased total operative times. CONCLUSIONS: Piezosurgery appears to have advantages over conventional rotary surgery for impacted wisdom tooth extraction in terms of quality of life and postoperative symptoms. However, further research should investigate potential drawbacks and confirm these findings.

Case Report: Novel Pathogenic Variant Detected in Two Siblings with Type 1 Gaucher Disease.

BACKGROUND: Gaucher disease (GD) is an autosomal recessive lysosomal storage disease. The disease develops due to glucocerebrosidase enzyme deficiency caused by biallelic pathogenic variants in the glucosylceramidase beta 1 (GBA1) gene, which encodes the glucocerebrosidase enzyme. The GBA1 gene is located at chromosomal location 1q22 and consists of 11 exons. In this article, we report a novel pathogenic variant in the GBA1 gene. CASE PRESENTATIONS: A 32-year-old female patient with no known chronic disease was admitted with complaints of weakness, bone pain, and abdominal pain. Her evaluation included hepatosplenomegaly, thrombocytopenia, osteoporosis, and anemia. The clinical suspicion of Gaucher disease was confirmed by glucocerebrosidase enzyme level and genetic testing. In her family screening, her sister also had hepato-splenomegaly, osteoporosis, thrombocytopenia, and anemia. Both sisters had no neurological symptoms. As a result of GBA1 gene sequence analysis in two of our patients, a missense variant was detected in the c.593C>A homozygous genotype. This variant has not been reported in any previously published case. CONCLUSION: In this case report, we aimed to contribute to the literature by reporting a new novel pathogenic variant in the GBA1 gene leading to type 1 Gaucher disease that has not been described before.

The evaluation of changes in maxillofacial bones using cone beam tomography in acromegaly.

BACKGROUND: The aim of the study was to evaluate the changes in craniofacial dimensions of newly diagnosed and untreated acromegaly patients, patients with non-functional pituitary adenoma and healthy individuals on Cone Beam Computed Tomography (CBCT). MATERIAL AND METHODS: 50 newly diagnosed acromegaly patients who did not receive any treatment for acromegaly were included in the study (Group A). Twenty patients with nonfunctional pituitary adenoma (Group B) and 30 healthy individuals were included (Group C). Linear, angular and volumetric measurements were performed. RESULTS: Mandibular length showed significant difference in acromegaly patients, and maxillar length statistically significant difference was found between the A-B and B-C (p> 0,05), no difference was found between the A-C (p<0,05). SNB and ANB angle was statistically different in all groups, while SNA angle was statistically different between group A-C and B-C. In volumetric measurements, a statistically significant difference was found between groups a-c and groups A-B (p< 0,05), no difference was found between groups B-C (p>0,05). CONCLUSIONS: CBCT measurements showed that mandibular volume and length were increased in the acromegaly group compared to the group B-C. Present study is the first research that compares acromegaly patients in respect to changes in maxillofacial dimensions.

Piperazine and piperidine-substituted 7-hydroxy coumarins for the development of anti-inflammatory agents.

Coumarins (2H-1-benzopyran-2-one), derivatives that can be isolated from several plants, have been reported for their anticoagulant, antimicrobial, anti-inflammatory, or anticancer activity. Some of these structures are currently approved for the treatment of cardiovascular diseases, as antibiotics or as an anticancer drug. Given the great potential of this structure and the limited number of studies that focus on molecules derived from carbon 8 of the benzopyranone heterocycle, we synthesized in this project 38 coumarin derivatives by substituting carbon 8 of the benzopyran ring with some aromatic and aliphatically substituted piperidines and piperazines. As a few of these structures were already shown to exhibit some carbonic anhydrase (CA) inhibition and as CA enzymes are reported to be closely related to inflammation, the synthesized derivatives were evaluated for their anti-inflammatory activity in vitro. The results indicated that compounds 20 and 31 revealed promising anti-inflammatory activity, as they demonstrated better activity than the reference drugs.

Do We Build Similar Molecules for Comorbid Diseases? Tevarud in Drug Design, an Analysis for Depression and Inflammation.

Tevarud designates two poets coincidently writing a same verse in the Ottoman Divan literature. This study aims to analyze the structural similarity of molecules independently designed for inflammation and depression to determine if coincidentally we are building similar molecules for comorbid diseases. For this purpose, a molecule library was first constituted with structures that were developed as anti-inflammatory (AI) and antidepressant (AD) agents these last decades. Then, the similarity of the structures was determined by calculating the Tanimoto and Cosine similarity coefficients for each AD/AI pair. The highest scores were obtained for two theophylline derivatives: AD17 (for which some AI activity was found to be mentioned) and AI42. The study also pointed out the similarity of some AD coumarins with some AI flavonoids interestingly found to be highly similar to some AI coumarins and AD flavonoids, respectively. Thus, our investigation demonstrated that structures independently developed as AD and AI derivatives can present extremely high structural similarity, a finding that can suggest mechanistic interconnection for these comorbid diseases and also guide for the design of novel bioactive compounds.

Investigation of Vitamin D levels in medical staff in a dental clinic.

AIMS: Recently, Vitamin D deficiency is pandemic now. The main reason of vitamin D deficiency is inadequate exposure to sunlight. Vitamin D level in nutrients is low and it can be ineffective to meet the daily requirements. Vitamin D is synthesized in the skin by ultraviolent radiation. In the present study, the authors aimed to investigate serum 25(OH) D levels of the medical staff working in different positions in the Faculty of Dentistry. SUBJECTS AND METHODS: A total of 51 dentists, 28 dental assistants, 11 secretaries, and 10 nurses working in the Faculty of Dentistry, Erciyes University between November and December 2014 were included to the study. The serum 25(OH) D levels of the participants were evaluated. RESULTS: Of the participants, 62 were females and 38 were males with a mean age of 30.17 ± 5.77 (range: 20-49) years. The mean vitamin D levels were found to be 12.1 ± 8.37 ng/mL (range: 2.1-38.3). A total of 51 participants had severe vitamin D insufficiency, while three participants had normal vitamin D levels with only one dentist. CONCLUSION: According to the results of present study, dental staff should be considered as a high-risk group for vitamin D deficiency. Vitamin D deficiency and insufficiency is a common problem among medical staffs as in several working groups such as white-collar workers and bankers. Results of present study suggest that insufficient exposure to the sunlight may lead to severe vitamin D deficiency in dental professionals. Vitamin D supplementation may be recommended to the dental staff.

Novel 8-Substituted Coumarins That Selectively Inhibit Human Carbonic Anhydrase IX and XII.

A novel series of 8-substituted coumarin-based compounds, characterized by the presence of alkylpiperazine and arylpiperazine chains, were synthesized and tested for their inhibitory activity against four human carbonic anhydrase (hCA) isoforms. All compounds displayed nanomolar potency against the cancer-related hCA IX and hCA XII; moreover, they were shown to be devoid of any inhibitory activity toward the cytosolic hCA I and hCA II up to 10 µM concentration in the assay system. Therefore, the synthesized coumarin ligands demonstrated to be potent and selective hCA IX/XII inhibitors, and were shown to be as potent as the reference inhibitor acetazolamide against hCA XII, with single-digit nanomolar Ki values. Molecular modeling studies provided a rationale for explaining the selectivity profile of these non-classic hCA inhibitors and their interactions with the enzymes, according to their specific mechanism of action, thus paving the way for future structure-based lead optimization studies.

Hypothalamic-pituitary-adrenal axis function in traumatic spinal cord injury-related neuropathic pain: a case-control study.

PURPOSE: This study aimed to investigate the hypothalamic-pituitary-adrenal (HPA) axis in spinal cord injury (SCI)-related neuropathic pain (NP) using dynamic adrenocorticotropic hormone (ACTH) stimulation tests. METHODS: This case-control study was conducted with 22 patients diagnosed with traumatic chronic spinal cord injury (15 with and 7 without neuropathic pain) and ten age- and sex-matched healthy control subjects. Collected data included socio-demographic variables, SCI characteristics, and level of NP using a numeric rating scale (NRS) and the Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS). HPA axis function was measured via low-dose (1 µg) and standard-dose (250 µg) ACTH tests (LDT and SDT, respectively). RESULTS: No significant differences existed regarding peak cortisol responses or area under the curve (AUC) of cortisol responses between the SCI patients with NP and healthy controls using LDT and SDT. In the SCI patients without pain, cortisol responses were significantly lower than those in the healthy controls for LDT and SDT. Peak cortisol and AUC responses of the LDT and SDT were positively correlated with NRS in SCI patients with NP. CONCLUSIONS: This study demonstrated that, in chronic SCI patients with NP, basal cortisol levels are relatively higher compared to healthy controls, and that HPA axis can be activated with low- and standard-dose ACTH stimulation tests. Although NP following SCI was not significantly associated with hypo- or hypercortisolemia, either after low- or standard-dose ACTH stimulation test, the severity of NP during chronic SCI may be positively associated with HPA axis activity.

The Importance of the Structural Similarity of Drugs Used for Depression and Inflammation, Two Comorbid Diseases.

Growing evidence links inflammation to depression and the combination of antiinflammatory drugs with an antidepressant to treat depressive symptoms is currently suggested. There are only few studies concerning the molecular mechanism underlying this comorbidity, and many of them point out the importance of the tryptophan pathway. There is yet no data that analyzes the structural similarity of the molecules used for the treatment of these comorbid diseases. This review aimed first to classify current antidepressant drugs and Non-steroidal Anti-inflammatory Drugs (NSAIDs) according to their structure. Molecules with two aromatic rings linked with a heteroatom or a carbonyl group (vortioxetine, ketoprofen, diclofenac), or presenting a naphtyl moiety in their structure (duloxetine, agomelatine, naproxen, nabumetone) were found to be structurally related. The antidepressant activity of these NSAIDs and the anti-inflammatory activity of these antidepressants were investigated. The literature search interestingly revealed reports indicating a serotonin-related antidepressant activity of the NSAIDs for structures found to be structurally similar to some antidepressants. Similarly, the antiinflammatory activity of the corresponding antidepressants was found to be correlated to the tryptophan metabolism pathway. These findings suggest a common molecular mechanism involved in both of the diseases and exhibit the importance of the molecular structure for a drug to be a potent antidepressant and/or anti-inflammatory agent.

COMPARISON OF FINASTERIDE, METFORMIN, AND FINASTERIDE PLUS METFORMIN IN PCOS.

The effects of finasteride on insulin resistance and of metformin on hyperandrogenism in patients with polycystic ovary syndrome (PCOS) are not clear. This study therefore compared the effects of finasteride, metformin, and finasteride plus metformin treatments on hormone levels, insulin resistance, and hirsutism score in women with PCOS. Fifty-two patients with PCOS were randomly assigned to receive finasteride 5 mg/day, metformin 1700 mg/day or finasteride plus metformin for 12 months. Body mass index (BMI), Ferriman Gallway score (FGS), serum concentrations of estradiol, sex hormone-binding globulin, free testosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and homeostasis model assessment of insulin resistance (HOMA-IR) index and areas under the curve (AUC) for insulin and glucose were evaluated before and after 12 months of treatment. Reductions in FGS, free testosterone, DHEAS, androstenedione, HOMA-IR, AUC-insulin, and AUC-glucose were significant within each group, whereas BMI and estradiol were not. Comparisons of changes in parameters in the 3 groups did not clearly show the superiority of any treatment modality. The treatment with finasteride alone significantly reduced both androgen levels and parameters of insulin resistance. In addition, metformin alone was effective, and not inferior to finasteride, in the treatment of hyperandrogenism.

The cysteine releasing pattern of some antioxidant thiazolidine-4-carboxylic acids.

Oxidative stress that corresponds to a significant increase in free radical concentration in cells can cause considerable damage to crucial biological macromolecules if not prevented by cellular defense mechanisms. The low-molecular-weight thiol glutathione (GSH) constitutes one of the main intracellular antioxidants. It is synthesized via cysteine, an amino acid found only in limited amounts in cells because of its neurotoxicity. Thus, to ensure an efficient GSH synthesis in case of an oxidative stress, cysteine should be provided extracellularly. Yet, given its nucleophilic properties and its rapid conversion into cystine, its corresponding disulfide, cysteine presents some toxicity and therefore is usually supplemented in a prodrug approach. Here, some thiazolidine-4-carboxylic acids were synthesized and evaluated for their antioxidant properties via the DDPH and CUPRAC assays. Then, the cysteine releasing capacity of the obtained compounds was investigated in aqueous and organic medium in order to correlate the relevant antioxidant properties of the molecules with their cysteine releasing pattern. As a result, the structures' antioxidative properties were not only attributed to cysteine release but also to the thiazolidine cycle itself.

Increased micronucleus, nucleoplasmic bridge, nuclear bud frequency and oxidative DNA damage associated with prolactin levels and pituitary adenoma diameters in patients with prolactinoma.

Prolactinoma is the most common pituitary tumor. Most pituitary tumors are benign, but they often are clinically significant. We investigated cytokinesis-block micronucleus cytome (CBMN cyt) assay parameters and oxidative DNA damage in patients with prolactinoma to assess the relations among age, prolactin level, pituitary adenoma diameter and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients with prolactinoma. We investigated 27 patients diagnosed with prolactinoma and 20 age- and sex-matched healthy controls. We measured CBMN cyt parameters and plasma 8-OHdG levels in peripheral blood lymphocytes of patients with prolactinoma and controls. The frequencies of micronucleus (MN), nucleoplasmic bridge, nuclear bud, apoptotic and necrotic cells, and plasma 8-OHdG levels in patients with prolactinoma were significantly greater than controls. MN frequency was correlated positively with age, prolactin levels and pituitary adenoma diameters in patients with prolactinoma. The increased chromosomal and oxidative DNA damage, and the positive correlation between MN frequency, prolactin levels and pituitary adenoma diameters may be associated with increased risk of cancer in patients with prolactinoma, because increased MN frequency is a predictor of cancer risk.

The Effects of Gonadotropin Replacement Therapy on Metabolic Parameters and Body Composition in Men with Idiopathic Hypogonadotropic Hypogonadism.

Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH.

Evaluation of the mutagenic and genotoxic effects of the ALC67 thiazolidine compound in Salmonella strains and human lymphocytes in vitro.

ALC67 is an N-acylated thiazolidine compound with promising anticancer activity that led to the recent discovery of a series of 3-propionyl thiazolidine-4-carboxylic acid ethyl esters as a family of novel antiproliferative agents. Since the mutagenic and genotoxic properties of marketed anticancer molecules constitute a main issue to be addressed, this study focused on the analysis of the mutagenicity, antimutagenecity, and genotoxicity of this molecule. The mutagenicity and antimutagenicity of ALC67 were evaluated by Ames test performed on Salmonella TA98 and TA100 strains. The genotoxicity of this molecule was investigated in the chromosomal aberration assay on human lymphocytes. All results revealed that the analyzed structure is not mutagenic in the two Salmonella strains tested and was not genotoxic in human lymphocytes in vitro On the other hand, it showed a weak antimutagenic effect in these two bacterial strains. The above results indicate that after performing some more mutagenicity assays using the other recommended strains, this compound can be safely used for the development of new structures exhibiting anticancer activities.

GENETIC DISORDERS OF PITUITARY DEVELOPMENT IN PATIENTS WITH SHEEHAN'S SYNDROME.

INTRODUCTION: Genetic disorders associated with the development of the pituitary gland and cranial bones may cause a genetic tendency toward Sheehan's syndrome (SS). Our aim in this study was to investigate expression disorders in the genes responsible for the development of the pituitary gland and cranial bones in patients with SS. MATERIALS AND METHODS: Forty-four patients who were previously diagnosed with SS and 43 healthy women were compared in terms of the mean expression values of genes including the prophet of PIT-1 (PROP1), HESX homeobox 1 (HESX1), POU class 1 homeobox 1 (POU1F1), LIM homeobox 3 (LHX3), LHX4, glioma-associated oncogene homolog 2 (GLI2), orthodenticle homeobox 2 (OTX2), SIX homeobox 3 (SIX3), SIX6, T-box transcription factor 19 (TBX19), transducin-like enhancer protein 1 (TLE1), TLE3, distal-less homeobox 2 (DLX2), DLX5, MSH homeobox 2 (MSX2), and paired box 3 (PAX3). RESULTS: The mean expression values of the HESX1, TLE1, TLE3, and MSX2 genes were significantly different in the SS group from the healthy control group, while the mean expression values of the remaining genes were similar. CONCLUSION: The present study concludes that abnormal expressions of HESX1, TLE1, TLE3, and MSX2 genes may cause a genetic predisposition to the development of SS.

Etiology of hypopituitarism in tertiary care institutions in Turkish population: analysis of 773 patients from Pituitary Study Group database.

Hypopituitarism in adult life is commonly acquired and the main causes are known as pituitary tumors and/or their treatments. Since there are new insights into the etiology of hypopituitarism and presence of differences in various populations, more studies regarding causes of hypopituitarism are needed to be done in different ethnic groups with sufficient number of patients. Therefore, we performed a multi-center database study in Turkish population investigating the etiology of hypopituitarism in 773 patients in tertiary care institutions. The study was designed and coordinated by the Pituitary Study Group of SEMT (The Society of Endocrinology and Metabolism of Turkey). Nineteen tertiary reference centers (14 university hospitals and 5 training hospitals) from the different regions of Turkey participated in the study. It is a cross-sectional database study, and the data were recorded for 18 months. We mainly classified the causes of hypopituitarism as pituitary tumors (due to direct effects of the pituitary tumors and/or their treatments), extra-pituitary tumors and non-tumoral causes. Mean age of 773 patients (49.8 % male, 50.2 % female) was 43.9 ± 16.1 years (range 16-84 years). The most common etiology of pituitary dysfunction was due to non-tumoral causes (49.2 %) among all patients. However, when we analyze the causes according to gender, the most common etiology in males was pituitary tumors, but the most common etiology in females was non-tumoral causes. According to the subgroup analysis of the causes of hypopituitarism in all patients, the most common four causes of hypopituitarism which have frequencies over 10 % were as follows: non-secretory pituitary adenomas, Sheehan's syndrome, lactotroph adenomas and idiopathic. With regard to the type of hormonal deficiencies; FSH/LH deficiency was the most common hormonal deficit (84.9 % of the patients). In 33.8 % of the patients, 4 anterior pituitary hormone deficiencies (FSH/LH, ACTH, TSH, and GH) were present. Among all patients, the most frequent cause of hypopituitarism was non-secretory pituitary adenomas. However, in female patients, present study clearly demonstrates that Sheehan's syndrome is still one of the most important causes of hypopituitarism in Turkish population. Further, population-based prospective studies need to be done to understand the prevalence and incidence of the causes of hypopituitarism in different countries.