Deletion of pancreatic ß-cell adenosine kinase improves glucose homeostasis in young mice and ameliorates streptozotocin-induced hyperglycaemia.

Severe reduction in the ß-cell number (collectively known as the ß-cell mass) contributes to the development of both type 1 and type 2 diabetes. Recent pharmacological studies have suggested that increased pancreatic ß-cell proliferation could be due to specific inhibition of adenosine kinase (ADK). However, genetic evidence for the function of pancreatic ß-cell ADK under physiological conditions or in a pathological context is still lacking. In this study, we crossed mice carrying LoxP-flanked Adk gene with Ins2-Cre mice to acquire pancreatic ß -cell ADK deficiency (Ins2-Cre± Adkfl/fl ) mice. Our results revealed that Ins2-Cre+/- Adkfl/fl mice showed improved glucose metabolism and ß-cell mass in younger mice, but showed normal activity in adult mice. Moreover, Ins2-Cre± Adkfl/fl mice were more resistant to streptozotocin (STZ) induced hyperglycaemia and pancreatic ß-cell damage in adult mice. In conclusion, we found that ADK negatively regulates ß-cell replication in young mice as well as under pathological conditions, such as STZ induced pancreatic ß-cell damage. Our study provided genetic evidence that specific inhibition of pancreatic ß-cell ADK has potential for anti-diabetic therapy.

Olfactory Change Pattern after Endoscopic Sinus Surgery in Chronic Rhinosinusitis with Olfactory Dysfunction.

OBJECTIVE: To determine the change pattern of olfactory function in chronic rhinosinusitis (CRS) with olfactory dysfunction after endoscopic sinus surgery (ESS), and its association with inspection scores. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Second Hospital of Shandong University, China, from December 2014 to January 2016. METHODOLOGY: Thirty-four CRS with nasal polyps (CRSwNP) patients and 14 CRS without nasal polyps (CRSsNP) patients were evaluated preoperatively by T&T olfactory test, olfactory VAS test, SNOT-20score and Lund-Mackay CT score. Outcomes were re-evaluated at 1 month, 3 months and 6 months postoperatively. RESULTS: Both olfactory and SNOT-20 scores showed significant improvement within 6 months in both CRSwNP and CRSsNP groups. Patients with anosmia in T&T test showed the largest degree of improvement. No significant recovery of olfactory dysfunction was observed at 1 month and 3 months in CRSsNP groups postoperative. In CRSwNP, the olfactory scores were correlated with the CT scores significantly (r=0.649, p<0.001; r=0.625, p<0.001). However, no correlation was found between the SNOT-20 score and olfactory score preoperatively. CONCLUSION: Our study has confirmed that the therapeutic effects of ESS on olfactory function last for up to 6 months, particularly in patients with CRSwNP. Although the therapeutic effects plateaued at 3 months postoperatively, the olfactory function continues to recover between 3 and 6 months.

Bone Age and Serum Osteocalcin Levels in Children With Obstructive Sleep Apnea Hypopnea Syndrome Before and After Adenotonsillectomy.

Our aim was to study the changes in bone age and serum osteocalcin levels before and after adenotonsillectomy (AT) in children with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 58 OSAHS children (37 males and 21 females) with the mean age of 6.68 ± 1.11 years were enrolled and assessed by x-ray-based bone age estimation and enzyme-linked immunosorbent assay-based measurement of serum osteocalcin levels, before surgery and 6 months after AT. SPSS 19.0 software was used for statistical analysis. Our results revealed that bone age and serum osteocalcin levels in OSAHS patients were significantly lower than normal controls before AT (P < 0.05). Within 6 months after surgery, the bone age and the serum osteocalcin levels were significantly elevated in OSAHS patients (P < 0.05), compared with those before surgery. Serum osteocalcin levels and bone age are negatively correlated with apnea-hypopnea index, oxygen desaturation index, the percentage of the total recorded time spent below 90% oxygen saturation, and Epworth sleepiness scale scores (all P < 0.05). Our findings suggested that bone age and serum osteocalcin levels may be correlated with the development of OSAHS in children. AT may improve bone age and serum osteocalcin levels in OSAHS children.

Adenotonsillectomy outcomes regarding bone age and osteocalcin in treatment of obstructive sleep apnea syndrome in children.

BACKGROUND: To investigate the effect of adenotonsillectomy (AT) on bone development, quality of life and polysomnography evaluation in children with obstructive sleep apnea syndrome (OSA). METHODS: Preoperative and postoperative (6 months) physical examination, PSG, bone age (BA) and osteocalcin (OC) evaluation were performed on the selected OSA children (n=92) and the healthy children (n=87). The OSA children were also scored based on the OSA 18-item questionnaire. A two-year follow-up was conducted to evaluate BA and OC changes. RESULTS: After AT, 81 (88.04%) OSA children recovered completely, eight (8.70%) achieved remarkable improvements, and three (3.26%) achieved moderate improvements. In the OSA children, postoperative OSA 18-item score and the scores of the five domains were significantly higher than preoperative ones. Compared with the preoperative, body mass index (BMI), weight for age Z-sores, height for age Z-sores, weight for height Z-sores and BMI Z-score in the OSA group 6 months after the operation were significantly increased, but no significant difference was detected between the OSA and the control group. The changes of BA and chronological age in the OSA group were significantly different from those in the control group. Two years after AT, BA between the two groups was no longer significantly different. Preoperative serum OC in the OSA group was lower than that in the control group, but increased to normal levels 6 months after AT. Correlation analysis showed serum OC levels were negatively correlated with apnea hyponea index, obstructive apnea index, arousal index, and lowest oxygen saturation. CONCLUSIONS: After AT, bone growth and development in children with OSA recovered gradually, and the serum OC levels decreased to the normal level. Therefore, preventive measures and positive treatments should be applied to minimize the negative effects of OSA in children.

Comparisons of thyroid hormone, intelligence, attention, and quality of life in children with obstructive sleep apnea hypopnea syndrome before and after endoscopic adenoidectomy.

Objective. The aim of this study was to compare the differences in thyroid hormone, intelligence, attention, and quality of life (QoL) of children with obstructive sleep apnea hypopnea syndrome (OSAHS) before and after endoscopic adenoidectomy. Method. A total of 35 OSAHS children (21 males and 14 females with a mean age of 6.81 ± 1.08 years) were included in this study for analyzing the levels of thyroid hormone, intelligence, attention, and QoL. There were 22 children underwent endoscopic adenoidectomy with bilateral tonsillectomy (BT), while the other 13 children who underwent endoscopic adenoidectomy without bilateral tonsillectomy without BT. Results. Our results revealed no significant difference in serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) levels in OSAHS children before and after endoscopic adenoidectomy (all P > 0.05). However, there were significant differences in full-scale intelligence quotient (FIQ) (92.45 ± 5.88 versus 106.23 ± 7.39, P < 0.001), verbal intelligence quotient (VIQ) (94.17 ± 15.01 versus 103.91 ± 9.74, P = 0.006), and performance intelligence quotient (PIQ) (94.12 ± 11.04 versus 104.31 ± 10.05, P = 0.001), attention (98.48 ± 8.74 versus 106.87 ± 8.58, P < 0.001), and total OSA-18 scores (87.62 ± 17.15 versus 46.61 ± 10.15, P < 0.001) between before and after endoscopic adenoidectomy in OSAHS children. Conclusion. Our findings provided evidence that the intelligence, attention, and QoL of OSAHS children may be significantly improved after endoscopic adenoidectomy.

Antiproliferative effects of celecoxib in Hep-2 cells through telomerase inhibition and induction of apoptosis.

BACKGROUND: To investigate the effect of celecoxib on telomerase activity and apoptosis in a human laryngeal squamous carcinoma cell line (Hep-2 cells). MATERIALS AND METHODS: The growth inhibition rate of Hep-2 cells in vitro was measured by MTT assay, and apoptosis by TUNEL assay and flow cytometry (FCM). The TRAP-ELISA method was used to determine telomerase activity in Hep-2 cells. The mRNA expression of human telomerase RNA component(hTR), human telomerase reverse transcriptase (hTERT) and human telomerase-associated protein(hTEP1) was determined by RT-PCR assay. Expression of Bax and Bcl-2 proteins was assessed by Western blotting. RESULTS: Celecoxib can inhibit proliferation and induce apoptosis in a dose- and time-dependent manner, repress telomerase activity, decrease hTERT mRNA and Bcl-2 protein expression and increase Bax protein expression, PGE2 had no effect on telomerase. CONCLUSIONS: Celecoxib had the antiproliferative and pro-apoptotic effect in Hep-2 cells. Apoptosis was accompanied by a decrease in telomerase activity which was directly correlated with hTERT mRNA and up-regulation of Bax/Bcl-2. Bcl-2 may thus play an important role in telomerase activity as well as apoptosis.