Synthesis, biological evaluation and in silico studies of novel thiadiazole-hydrazone derivatives for carbonic anhydrase inhibitory and anticancer activities.

Thiadiazole and hydrazone derivatives (5a-5i) were synthesized and their chemical structures were verified and described by 1H NMR, 13C NMR, and HRMS spectra. Three cancer cell lines (MCF-7, MDA, and HT-29) and one healthy cell line (L929) were used to test the cytotoxicity activity of synthesized compounds as well as their inhibitory activity against carbonic anhydrase I, II and IX isoenzymes. Compound 5d (29.74 µM) had a high inhibitory effect on hCA I and compound 5b (23.18 µM) had a high inhibitory effect on hCA II. Furthermore, compound 5i was found to be the most potent against CA IX. Compounds 5a-5i, 5b and 5i showed the highest anticancer effect against MCF-7 cell line with an IC50 value of 9.19 and 23.50 µM, and compound 5d showed the highest anticancer effect against MDA cell line with an IC50 value of 10.43 µM. The presence of fluoro substituent in the o-position of the phenyl ring increases the effect on hCA II, while the methoxy group in the o-position of the phenyl ring increases the activity on hCA I as well as increase the anticancer activity. Cell death induction was evaluated by Annexin V assay and it was determined that these compounds cause cell death by apoptosis. Molecular docking was performed for compounds 5b and 5d to understand their biological interactions. The physical and ADME properties of compounds 5b and 5d were evaluated using SwissADME.

Video game-based therapy for the non-dominant hand improves manual skills and grip strength.

The study was designed to investigate the effect of virtual reality-supported training on manual skills and grip strength in the non-dominant hand in healthy participants. Thirty participants were randomized into two groups: ErgoActive group (n=15) and control group (n=15). The ErgoActive study group received 8 weeks of training with leap motion controller-based virtual reality games. The training was done 1 day per week for 30min. The participants' hand function was evaluated using the Jebsen Taylor Hand Function Test (JTHFT), while grip strength was evaluated with a Jamar Hand Dynamometer and Pinchmeter. After 8 weeks, the ErgoActive and control groups had significantly different JTHFT, Jamar and Pinchmeter results (P<0.05). When leap motion controller-based virtual reality applications are used, healthy subjects have increased manual skills and grip strength in their non-dominant hand. These virtual reality games are an effective and fun way of improving patients' hand functions.

Recombinant adiponectin inhibits inflammation processes via NF-kB pathway in acute pancreatitis.

PURPOSE:   Adiponectin is a protein stemming from adipose tissue and having strong anti-inflammatory properties. We aimed to assess the damage diminishing effects of recombinant adiponectin  (rAD) through NF-kB in the experimental acute pancreatitis  (AP) model. MATERIALS AND METHODS:   Acute pancreatitis was created by applying 50 µg/kg dose of intraperitoneal cerulean. The rats were randomised and divided into 3 groups as control, AP and rAD groups. Moreover, the rats in each group were divided into two sub-groups as 24th and 48th hour subgroups. rAD was injected in the study group intraperitoneally. Tissue and blood samples were taken after 24 and 48 hours. Histopathological assessment and NF-kB activity were investigated in pancreatic tissue. RESULTS:   Serum TNF-a, IL-1b and IL-6 levels were found to be statistically significant in the AP group compared to the rAD group in the 24th and 48th hour  (p < 0.05). Similarly, NF-kB activity was also found to be significant in the AP group both in the 24th and 48th hour  (p < 0.05). There were significant differences in the AP and the rAD groups histopathologically in terms of edema, inflammation, vacuolisation and necrosis  (p < 0.001). CONCLUSION:   rAD has significantly reduced NF-kB activity, cytokine levels and tissue damage  (Tab. 1, Fig. 1, Ref. 51).

Investigation of the effects of thymoquinone on erythrocyte deformability in sepsis treatment which created by cecal perforation in rat.

AIM: We aimed to study the effects of thymoquinone on erythrocyte deformability in an experimental model of sepsis given before or after the initiation of the sepsis model. METHOD: The animals were grouped as (n = 6) control, nigella sativa, sepsis, sepsis group with administration of nigella sativa before sepsis development and sepsis group with nigella sativa administration after sepsis development. Cecal ligation and puncture model (CLP) was used to induce sepsis in the animals. The thymoquinone was given 1 hour before or after the CLP in the study groups with a dose of 500 mg·kg(-1). Erythrocyte deformability and relative resistance was calculated. RESULT: Relative resistance was increased in the sepsis groups when compared to the control group (p < 0.0001). Deformability index was increased in the sepsis group when compared to the other groups (p < 0.0001 in all groups). Sepsis group with after nigella sativa groups deformability index was significantly different from the deformability index in control group (p = 0.002). The use of nigella sativa before the initiation of sepsis corrected the deformability index significantly and the results were comparable to the control group (p = 0.078). CONCLUSION: Thymoquinone administration before induction of CLP was observed to have protective effects on these alterations in CLP sepsis (Tab. 1, Fig. 1, Ref. 26).

Candesartan mediates microcirculation in acute necrotizing pancreatitis.

AIM: In the present study we aimed to determine the effect of an AT-II antagonist candesartan on pancreatic microcirculation in an experimental model of acute necrotizing pancreatitis. MATERIALS AND METHODS: There were five study groups with 10 animals in each. Pancreatitis was induced by intravenous infusion of cerulein and coadministration of glycodeoxycholate into biliopancreatic canal. Candesartan is given at 6th and 18th hour to the 24th and 48th hour groups, respectively. At 24th and 48th hours; following anaesthesia laparotomy was performed and laser Doppler flowmetry was performed in the pancreatic tissue of the animals. Following scarification blood samples were obtained for amylase, myeloperoxidase, IL-6 and tumour necrosis factor alpha. Tissue samples from the pancreas were obtained for histopathological analysis, endothelial cell apoptosis (TUNEL assay) and matrix metalloproteinase-9 immunohistochemistry. RESULTS: Pancreatic microcirculation was higher in the candesartan treated groups (p < 0.05). Myeloperoxidase, IL-6 and tumour necrosis factor alpha was found to be lower in the candesartan treated groups (p < 0.05). The pancreatic edema and inflammation were found to be reduced in the candesartan treated groups (p < 0.05). Endothelial apoptosis was found to be reduced by cadesartan treatment but it did not reach statistical significance (p > 0.05). Tissue matrix metalloproteinase -9 levels were found to be reduced with candesartan treatment (p < 0.05). CONCLUSION: Treatment with candesartan in the early phases of acute necrotizing pancreatitis effective on microcirculation of pancreatic tissue (Tab. 3, Fig. 6, Ref. 28).

MicroRNA -143 and -223 in obesity.

BACKGROUND: Obesity alters endocrine and metabolic functions of adipose tissue and has been recognized as a chronic inflammatory disease, which in turn may contribute to the development of insulin resistance, type 2 diabetes, obesity-associated vasculopathy and cardiovascular disease. The pathogenesis of obesity involves many regulatory pathways including transcriptional regulatory networks, including microRNAs. METHODS: A total of 83 patients were included in the study. Patients were recruited from a cardiology outpatient clinic and were allocated into 3 age- and sex-matched groups according to their body mass index. Group 1 included 23 morbidly obese, group 2 30 obese, and group 3 30 normal or overweight subjects. RESULTS: In our study, we showed that miR-143 and miR-223 levels were significantly lower in groups 1 and 2 than the control group (normal BMI or overweight). CONCLUSIONS: Obesity leads to alterations in miRNA expressions and miRNA-143 and -223s can be used as biomarkers for the metabolic changes in obesity.

Periodontal status and post-transplantation complications following intensive periodontal treatment in patients underwent allogenic hematopoietic stem cell transplantation conditioned with myeloablative regimen.

OBJECTIVES: Evaluation of the periodontal status is necessary prior to management with high-dose chemotherapy before hematopoietic stem cell therapy (HSCT). During medical therapy, pre-existing periodontal conditions may exacerbate and cause local and systemic complications. When possible, maximal oral health should be achieved prior to engraftment. In this study, we aimed to determine the alterations occurred in the periodontal status of the patients after periodontal treatment and allogenic HSCT and evaluate the effect of intensive periodontal approach on the short-term complications of HSCT. METHODS: The alterations occurred in the periodontal tissues 3-4 weeks after periodontal treatment and after HSCT periods of 3 months for 29 patients treated with full-mouth periodontal treatment completed in 24 h in addition to eradication of dental foci, and oral hygiene status were evaluated using pocket depth measurements, presence of bleeding on probing and plaque and gingival indices. The incidence and severity of acute graft-versus-host disease (GVHD) and oral mucositis (OM) were recorded. Duration of engraftment period and the episode of febrile neutropenia were also evaluated. RESULTS: There were significant improvements in periodontal status after periodontal treatment (P<0.001). There were 14 (48.3%) patients without acute GVHD and 17 (58.6%) patients with no sign of OM. The majority of OM was at grade II level. There was a negative relation that exists between the percentage of BOP (+) sites and presence of OM (r=-0.518, P<0.05). CONCLUSIONS: Together with a significant reduction in gingival inflammation and maintenance of the improvement in periodontal health, remarkable decrease in the incidence and severity of OM were observed.

Gastrocolic fistula as a complication after gastrojejunostomy.

Gastrocolic fistula formation is an extremely rare complication of gastric ulcer disease. We report a case of a 55-year-old man who presented with a two-month history of abdominal discomfort, postprandial diarrhea, nausea and faecal vomiting. Upper gastrointestinal endoscopy showed an ulcer in the greater curvature of the stomach. Barium enema examination revealed an obvious gastrocolic fistula between the greater curvature of the stomach and the transverse colon. The involved segment of the colon was excised and truncal vagotomy and antrectomy was performed. The patient was discharged on the 7th postoperative day. It is concluded that cases with postprandial diarrhea and nutritional disturbances after gastric surgery should remind us of the probability of gastrocolic fistula formation.

L-alanin-L-glutamine supplementation improves the outcome after colorectal surgery for cancer.

OBJECTIVE: To investigate the effect of l-alanine-l-glutamine (Gln) on postoperative complication rate and duration of hospitalization in patients operated for colorectal cancer. METHOD: A total of 109 patients operated with the diagnosis of colorectal cancer and given enteral nutrition between January 2001 and January 2005 were prospectively analysed. The patients were randomized and analysed in two groups; Gln group (n = 57): patients were given parenteral Gln (1 g/kg/day, Dipeptiven, Fresenuis Kabi, Germany) together with enteral nutrition (Ensure; Abbott, Zwolle, The Netherlands) and the control group (n = 52) only received enteral nutrition (Ensure; Abbott), which was a standard isonitrogenous and isocaloric formula. The supplemental enteral nutrition was provided for at least 5 days pre- and postoperatively according to the nutritional status of the patients. Age, gender, subjective global assessment (SGA), body mass index (BMI), serum albumin, protein, associated disorders, localization of pathology, techniques of anastomosis, postoperative complications and length of hospital stay were analysed for each patient. RESULTS: The duration of nutritional support in the Gln group was 6 +/- 2 and 5 +/- 1 days pre- and postoperatively; while it was 7 +/- 1 and 6 +/- 1 days for the control group, and there were no significant difference among the groups (P > 0.05). Age, gender, SGA, BMI, levels of serum albumin and protein, localization of pathology and techniques of anastomosis were also similar (P > 0.05). Wound infection (P = 0.038), intraabdominal abcess formation (P = 0.044) and wound dehiscence (P = 0.044) were significantly higher in the control group than in the Gln group. There was no significant difference in terms of anastomotic leakage and other complications between both groups (P > 0.05). Hospital stay was significantly shorter in the Gln group (P < 0.001). CONCLUSION: Supplementation of parenteral Gln decreased the postoperative complications and hospital stay and in the patients undergoing the colorectal surgery for cancer.

Morphological changes in diseased cementum layers: a scanning electron microscopy study.

The aim of this study was to compare the morphological changes that occurred in root cementum layers due to periodontal disease by using scanning electron microscopy (SEM). Ninety-two periodontally hopeless teeth extracted from 29 patients were studied. Measurements of probing depth (PD) and clinical attachment loss (CAL) were taken prior to extractions. After the longitudinal fracturing process of root specimens, healthy and diseased cementum layers of roots were evaluated by SEM for the thickness of the cementum and the morphological changes in collagen fibers. The result of SEM evaluation revealed a significant ( P < 0.001) decrease in the thickness of cementum layer on the diseased root surfaces compared to the healthy surfaces. There were denser and conspicuous collagen fibers with their interfibrillar matrix in cementum layers on the healthy root surfaces compared to the diseased surfaces. Within the limits of this study, the thickness of cementum layers in diseased areas was found to be significantly less than that in the healthy areas of root surfaces. However, there exist variations in the density and visibility of cemental fibers between individuals and within the individual.

Does temporary splinting before non-surgical therapy eliminate scaling and root planing-induced trauma to the mobile teeth?

The objective of this study was to determine whether temporary splinting of periodontitis-affected mobile teeth, prior to non-surgical mechanical therapy, affects treatment outcome by eliminating scaling and root planing-induced trauma to the teeth. Mandibular anterior teeth of 29 patients (15 females; 14 males; age range 30 to 48 years) with adult periodontitis were evaluated. Clinical measurements were performed at 4 sites per tooth including mesial, distal, buccal and lingual aspects at baseline, 3 and 6 months after treatment. The following clinical parameters were analyzed: plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), probing attachment level (PAL), gingival margin level (GML) and tooth mobility (TM). Patients were randomly divided into 3 groups: i) group 1 (n = 8) received scaling and root planing (SRP) only, ii) group 2 (n = 10) received scaling and root planing before splinting and iii) group 3 (n = 11) received scaling and root planing after splinting. Statistical analysis revealed that there were no significant differences among the groups for either bleeding on probing or probing attachment level values at any of the time intervals. At the end of the study, the greatest decrease in pocket depth was noted in group 2 (1.24+/-0.10 mm) which was thought to be the result of gingival recession (0.73+/-0.07 mm). Group 1 was the only group that showed reduction in tooth mobility at 3 months compared to baseline (1.67+/-0.55 PTV units). Group 3 displayed the least reduction in tooth mobility during the entire study period (0.26+/-0.44 PTV units). In conclusion, splinting of mobile teeth before SRP, and thereby elimination of potential SRP-induced trauma to the mobile teeth, did not show any adjunctive effect on healing when compared to splinting after SRP. Thorough debridement of root surfaces, even performed in the presence of increased mobility, resulted in improvements in clinical parameters, i.e. mechanical manipulation of mobile teeth during periodontal treatment did not affect clinical outcome negatively.

Estrogen and progesterone receptors in the peripheral giant cell granulomas of the oral cavity.

Peripheral giant cell granulomas are common proliferative lesions of the oral cavity with a predilection for females. In this study, the presence of estrogen and progesterone receptors in 26 peripheral giant cell granuloma cases were studied utilizing the immunoperoxidase technique. In fourteen cases, estrogen receptor positivity was found in stromal cells. In ten of these, osteoclast-type giant cells also exhibited estrogen receptor immunostaining. Progesterone receptor expression was not detected. It was concluded that the cells forming peripheral giant cell granuloma are potential targets for estrogens and that these lesions might be conditioned by sex hormones.

Gingival Langerhans' cells in type I diabetes mellitus.

Langerhans' cells (LCs) are intraepithelial immunocompetent cells. Changes in the number of LCs occur in inflammatory and autoimmune diseases. In this study, the number of gingival LCs in patients with type I diabetes mellitus was compared with those of normal individuals using immunohistochemical methods. Gingival biopsies were obtained from 20 type I diabetics and 10 healthy individuals. Anti-CD1 positive LCs formed an intraepithelial network and showed a marked increase in type I diabetics. This increase was not related to diabetic age. The number of LCs was proportional to the density of subepithelial inflammatory cells. Our findings suggest that LCs may play a role in the development of diabetic gingivitis.

Familial gingival fibromatosis with unusual histologic findings.

This article describes the occurrence of numerous calcifications, amyloid deposits, and islands of odontogenic epithelium in the gingiva of 3 siblings with familial gingival fibromatosis. These microscopic features have not been reported previously in patients with this condition.

Generalized gingival enlargement due to accumulation of amyloid-like material.

Hyaline or amyloid-like substances may be seen in several oral lesions. Some of these originate from epithelial cells and some from connective tissue components. In this study, amyloid-like material causing gingival enlargement in three patients, with eyelid involvement in two, was examined using histochemistry, immunohistochemistry and electron microscopy. These accumulations did not share the classical features of amyloid such as green birefringence under polarized light after Congo red staining. Our findings suggest that epithelial degeneration plays an important role in the pathogenesis of these amyloid-like accumulations. These substances may be the result of defective amyloidogenesis and our cases may represent an oral counterpart of ligneous conjunctivitis or colloid milium of the skin.

Long-term evaluation of surgical periodontal treatment with and without maintenance care.

A study was conducted on the effectiveness of individual maintenance recalls and the long-term effects of surgical therapy on pocket depth and tooth loss in 43 patients with moderate to advanced periodontal disease. Sixteen of the patients had periodic control and 27 were uncontrolled. Intervals of periodic recall ranged from 3 to 6 months according to individual needs. Pocket depths were measured from four aspects of each tooth and initially classified as shallow (1-3 mm), moderate (4-6 mm) or deep (7 mm or more). Changes in each pocket depth level were determined after 10 years. Tenth-year comparisons showed that the uncontrolled group had significantly higher mean pocket depth values. Tooth loss rate was 3.6% in the controlled group, and 14.1% in the uncontrolled group, and the mean numbers of lost teeth were 0.69 and 3.63, respectively, in the ten-year period. It was concluded that periodic recalls were essential for long-term success of periodontal surgery.

Mast cells in periodontal disease.

Since the roles of mast cells in periodontal tissues are not clear, this study aimed to count the number of mast cells in gingival tissues of healthy volunteers and patients with chronic periodontal disease before and three weeks after surgical treatment. The numbers of mast cells were found to be increased on postoperative healed tissues and inflamed tissues respectively, compared to healthy tissues. This increase is closely related to fibrosis in connective tissues.

New attachment formation following periodontal surgery in a dog.

We evaluated new attachment following treatment of experimental periodontitis in a canine model. Periodontal destruction was induced over an 8-month period using silk ligatures and a soft diet, and this remained stable for 170 days before surgery. After surgical scaling and root planing of eight bicuspid teeth, the apical end of the pockets was estimated using an occlusal stent and a periodontal probe, then marked with a blade. The root surfaces of three bicuspids were treated with citric acid for 3 min, and tetracycline salt was applied to the root surfaces of two teeth. The remaining three bicuspids served as controls. Postoperatively, no attempts were made to improve oral hygiene, and on day 48 light microscopic examination of biopsy materials revealed new attachment in all treated teeth. However, in some sections new cementum and new collagen formation was much more extensive and complete in both groups of experimental teeth than in the control teeth.

[Mast cell counting in fibrous gingival hyperplasias and giant cell granuloma]. / Fibröz diseti hiperplazileri ve dev hücreli granulomlarda mast hücre sayimi.

Mast cells are the normal components of the connective tissues and they are found particularly in perivascular areas. They have a primary role in hypersensitivity reactions and inflamatuar process. They are found in whole healthy and inflamed periodontal tissues. Number of mast cells increase in some connective tissue tumors. However the roles of mast cells in fibrous gingival hyperplasias and giant cell granulomas of gingiva, is not clear. In this study, the number of mast cells were counted in both lesion groups. Numbers of mast cells were found increased on gingival fibrous hyperplasias, comparing to normal connective tissues and giant cell granulomas.

[Long term effects of surgical and non-surgical periodontal treatment. 1. Attachment level changes]. / Cerrahi olan ve olmayan periodontal tedavilerin uzun süreli etkilerinin degerlendirilmesi. I. Atasman düzeyi degisimleri.

The long term effectiveness of modified Widman flap and subgingival curettage techniques were evaluated in 21 patients who have chronic periodontitis. Individual acrylic reference plates and a color coded WHO probe were used for attachment level measurements. Attachment level changes which were determined in 3 rd, 6th, and 9th months calculated as percentage gain or loss of initial attachment level and compared statistically. Initially shallow pockets showed loss of attachment in both techniques. There was significant attachment gain in initially moderate and deep pockets. Accordingly, attachment gain occurred at facial, interproximal and oral surfaces with both techniques. It can be concluded that if the effective plaque control would be maintained post operatively, subgingival curettage is the first choice of method in the treatment of periodontal pockets.