The relationship of tongue fat content and efficacy of uvulopalatopharyngoplasty in Chinese patients with obstructive sleep apnea.

BACKGROUND: To investigate the relationship between tongue fat content and severity of obstructive sleep apnea (OSA) and its effects on the efficacy of uvulopalatopharyngoplasty (UPPP) in the Chinese group. METHOD: Fifty-two participants concluded to this study were diagnosed as OSA by performing polysomnography (PSG) then they were divided into moderate group and severe group according to apnea hypopnea index (AHI). All of them were also collected a series of data including age, BMI, height, weight, neck circumference, abdominal circumference, magnetic resonance imaging (MRI) of upper airway and the score of Epworth Sleepiness Scale (ESS) on the morning after they completed PSG. The relationship between tongue fat content and severity of OSA as well as the association between tongue fat content in pre-operation and surgical efficacy were analyzed.Participants underwent UPPP and followed up at 3rd month after surgery, and they were divided into two groups according to the surgical efficacy. RESULTS: There were 7 patients in the moderate OSA group and 45 patients in the severe OSA group. The tongue volume was significantly larger in the severe OSA group than that in the moderate OSA group. There was no difference in tongue fat volume and tongue fat rate between the two groups. There was no association among tongue fat content, AHI, obstructive apnea hypopnea index, obstructive apnea index and Epworth sleepiness scale (all P > 0.05), but tongue fat content was related to the lowest oxygen saturation (r=-0.335, P < 0.05). There was no significantly difference in pre-operative tongue fat content in two different surgical efficacy groups. CONCLUSIONS: This study didn't show an association between tongue fat content and the severity of OSA in the Chinese group, but it suggested a negative correlation between tongue fat content and the lowest oxygen saturation (LSaO2). Tongue fat content didn't influence surgical efficacy of UPPP in Chinese OSA patients. TRIAL REGISTRATION: This study didn't report on a clinical trial, it was retrospectively registered.

Association between obstructive sleep apnea and thyroid function: A 10-year retrospective study.

PURPOSE: To explore whether the obstructive sleep apnea (OSA) has an impact on thyroid function in patients. METHOD: The data of 853 patients were retrospectively collected from the Second Affiliated Hospital of Xi'an Jiaotong University in recent ten years. All the objects were divided into the control group, mild-moderate and severe OSA groups according to the result of polysomnography. RESULTS: In the non-elderly population (age <60), there were significant differences in serum free triiodothyronine (FT3) and total triiodothyronine (TT3) between the mild-moderate and severe OSA groups (all p < 0.05). And there were differences in serum total thyroxine, anti-thyroid peroxidase, and antithyroglobulin between the control and mild-moderate OSA groups (all p < 0.05). Moreover, FT3 was associated with age (OR = 0.98, p < 0.05) and apnea-hypopnea index (OR = 1.01, p < 0.05). The occurrence of thyroid nodules was associated with average transcutaneous oxygen saturation (Mean SaO2) (OR = 0.97, p < 0.05). In the elderly (age ≥60), there was no difference in FT3 and TT3 between the mild-moderate and severe OSA. While the occurrence of thyroid nodules was also associated with Mean SaO2 (OR = 0.90, p < 0.05). CONCLUSION: In the non-elderly population, the progress of OSA may promote the increase in thyroid hormone (especially FT3) levels, while in the elderly population not. In the whole age population, Mean SaO 2 is associated with the occurrence of thyroid nodules. Future research on the relationship between OSA and thyroid function, and age stratification is necessary.

Prediction model of obstructive sleep apnea-related hypertension: Machine learning-based development and interpretation study.

Background: Obstructive sleep apnea (OSA) is a globally prevalent disease closely associated with hypertension. To date, no predictive model for OSA-related hypertension has been established. We aimed to use machine learning (ML) to construct a model to analyze risk factors and predict OSA-related hypertension. Materials and methods: We retrospectively collected the clinical data of OSA patients diagnosed by polysomnography from October 2019 to December 2021 and randomly divided them into training and validation sets. A total of 1,493 OSA patients with 27 variables were included. Independent risk factors for the risk of OSA-related hypertension were screened by the multifactorial logistic regression models. Six ML algorithms, including the logistic regression (LR), the gradient boosting machine (GBM), the extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and the multilayer perceptron (MLP), were used to develop the model on the training set. The validation set was used to tune the model hyperparameters to determine the final prediction model. We compared the accuracy and discrimination of the models to identify the best machine learning algorithm for predicting OSA-related hypertension. In addition, a web-based tool was developed to promote its clinical application. We used permutation importance and Shapley additive explanations (SHAP) to determine the importance of the selected features and interpret the ML models. Results: A total of 18 variables were selected for the models. The GBM model achieved the most extraordinary discriminatory ability (area under the receiver operating characteristic curve = 0.873, accuracy = 0.885, sensitivity = 0.713), and on the basis of this model, an online tool was built to help clinicians optimize OSA-related hypertension patient diagnosis. Finally, age, family history of hypertension, minimum arterial oxygen saturation, body mass index, and percentage of time of SaO2 < 90% were revealed by the SHAP method as the top five critical variables contributing to the diagnosis of OSA-related hypertension. Conclusion: We established a risk prediction model for OSA-related hypertension patients using the ML method and demonstrated that among the six ML models, the gradient boosting machine model performs best. This prediction model could help to identify high-risk OSA-related hypertension patients, provide early and individualized diagnoses and treatment plans, protect patients from the serious consequences of OSA-related hypertension, and minimize the burden on society.

NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia.

BACKGROUND: Obstructive sleep apnea (OSA) is mainly characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), the latter one being associated with multiple organ injury. Recently, OSA-induced cognition dysfunction has received extensive attention from scholars. Astrocytes are essential in neurocognitive deficits via A1/A2 phenotypic changes. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining neuroinflammation. However, whether the NLRP3 regulates the A1/A2 transformation of astrocytes in CIH-related brain injury remains unclear. METHODS: We constructed an OSA-related CIH animal model and assessed the rats' learning ability in the Morris water maze; the histopathological assessment was performed by HE and Nissl staining. The expression of GFAP (astrocyte marker), C3d (A1-type astrocyte marker), and S100a10 (A2-type astrocyte marker) were detected by immunohistochemistry and immunofluorescence. Western blotting and RT-qPCR were used to evaluate the changes of A1/A2 astrocyte-related protein and NLRP3/Caspase-1/ASC/IL-1ß. RESULTS: The learning ability of rats decreased under CIH. Further pathological examination revealed that the neurocyte in the hippocampus were damaged. The cell nuclei were fragmented and dissolved, and Nissl bodies were reduced. Immunohistochemistry showed that astrocytes were activated, and morphology and number of astrocytes changed. Immunofluorescence, Western blotting and RT-qPCR showed that the expression of C3d was increased while S100a10 was decreased. Also, the expression of the inflammasome (NLRP3/Caspase-1/ASC/IL-1ß) was increased. After treatment of MCC950 (a small molecule inhibitor of NLRP3), the damage of nerve cells was alleviated, the Nissl bodies increased, the activation of astrocytes was reduced, and the expression of A2-type astrocytes was increased. In contrast, A1-type astrocytes decreased, and the expression of inflammasome NLRP3/Caspase-1/ASC/IL-1ß pathway-related proteins decreased. CONCLUSION: The NLRP3 inflammasome could regulate the A1/A2 transformation of astrocytes in brain injury induced by CIH.

Serum neurofilament light reflects cognitive dysfunctions in children with obstructive sleep apnea.

BACKGROUND: In children, obstructive sleep apnea (OSA) can cause cognitive dysfunctions. Amyloid-beta and tau are elevated in OSA. Neurofilament light (NfL) is a marker of neuro-axonal damage, but there are no reports of NfL for OSA. The objective was to investigate the serum levels of NfL and tau in children with or without OSA and explore their relationship with cognitive dysfunctions caused by OSA. METHODS: This retrospective case-control study included children diagnosed with adenoid tonsil hypertrophy from July 2017 to September 2019 at the Second Affiliated Hospital of Xi'an Jiaotong University. Correlations between cognitive scores and tau and NfL were examined. RESULTS: Fifty-six OSA and 49 non-OSA children were included. The serum NfL levels were higher in the OSA group (31.68 (27.29-36.07) pg/ml) than in the non-OSA group (19.13 (17.32-20.95) pg/ml) (P < 0.001). Moreover, NfL was correlated with the course of the disease, apnea-hypopnea index (AHI), obstructive apnea index (OAI), obstructive apnea-hypopnea index (OAHI), average oxygen saturation (SaO2), respiratory arousal index (RAI), and cognitive dysfunctions evaluated by the Chinese Wechsler Intelligence Scale for Children (C-WISC) (all P < 0.05). The area under the receiver operating characteristics curve (AUC) of NfL was 0.816 (95%CI: 0.736-0.897). Multiple regression analysis revealed that NfL was significantly associated with verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ) and full-scale intelligence quotient (FIQ) (P < 0.001, respectively). CONCLUSIONS: Serum NfL levels are associated with the severity of cognitive dysfunctions in children diagnosed with adenoid tonsil hypertrophy and might be a candidate noninvasive, objective marker to identify cognitive dysfunctions in children with OSA.

[Clinical features, diagnosis and treatment for patients presenting with granulation tissue of the external auditory canal].

Objective:To explore the clinical characteristics and diagnosis and treatment in the patients presenting with granulation tissue of the external auditory canal. Methods:The data of 71 postoperative patients presenting with granulation tissue of the external auditory canal in the Department of Otolaryngology, the First Affiliated Hospital of the Air Force Military Medical University from January 2015 to June 2020 were analyzed retrospectively, including the chief complaint, physical examination, auxiliary examination and preoperative imaging, biopsy was performed when necessary to confirm the diagnosis. Among the 71 patients, 30 cases were diagnosed as chronic otitis media, 19 cases were external auditory canal cholesteatoma, 5 cases were external auditory canal carcinoma, 6 cases were paraganglioma, 1 case was granulomatous hemangioma, 1 case was first branchial cleft fistula, 4 cases were granuloma of the external auditory canal, 4 cases were hemangioma of the external auditory canal, and 1 case was foreign body of the external auditory canal. Individualized treatment plans are made according to the characteristics and extent of the lesions. Results:Postoperative follow-up was 12 to 74 months, with an average of （44±18.1） months. Seventy patients（98.6%） had no complications such as sensorineural deafness, external auditory stenosis or peripheral facial paralysis after surgery, and one patient with paraganglioma had postoperative neurological function grade Ⅱ, and was treated with nutritional nerves, and the postoperative neural function recovered to grade Ⅰ after 3 months. Conclusion:The patients presenting with granulation tissue of the external auditory canal can be diagnosed as various diseases. It is necessary to analyze the patient's medical history in detail, confirm the diagnosis in combination with imaging examination, and formulate an individualized treatment plan to reduce misdiagnosis and missed diagnosis.

Relationship between serum brain-derived neurotrophic factor and cognitive impairment in children with sleep-disordered breathing.

Background: As an important neuroprotective factor, the brain-derived neurotrophic factor (BDNF) may have a key role in cognitive impairment in children with sleep-disordered breathing (SDB). The main aim of this study was to compare the levels of BDNF and tyrosine kinase receptor B (TrkB) in normal children and those with obstructive sleep apnea (OSA) and primary snoring (PS) and to explore a possible link between BDNF/TrkB, inflammation, and SDB with cognitive impairment in children. Methods: A total of 44 OSA children and 35 PS children who completed polysomnography between October 2017 and October 2019 were enrolled. At the same time, 40 healthy children during the same period were included as a control. Enzyme-linked immunosorbent assay was used to measure serum indices of BDNF, TrkB, interleukin-1beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Correlation and pooled analyses were performed between the cognitive scores and four serological indicators. Logistic regression was used to analyze the risk factors for cognitive impairment. Results: Significant differences were found in serum BDNF, TrkB, IL-1ß, and TNF-α between the three groups (all P < 0.01). The serum BDNF and TrkB in the OSA and PS groups were lower than those in the control group, whereas the serum IL-1ß and TNF-α were higher than those in the control group (all P < 0.05). Moreover, among these four indices, the strongest correlation was found between BDNF and the Chinese Wechsler Intelligence Scale (all P < 0.05). Logistic regression analysis revealed a correlation between OSA status, TrkB, and course of mouth breathing and cognitive status. Conclusion: The levels of serum BDNF and TrkB were related to cognitive impairment in children with SDB. Also, BDNF and TrkB could be used as noninvasive and objective candidate markers and predictive indices of cognitive impairment in children with SDB.

Assessment of event-related evoked potentials and China-Wechsler intelligence scale for cognitive dysfunction in children with obstructive sleep apnea.

OBJECTIVE: To explore the relationship between obstructive sleep apnea (OSA) and cognitive impairment by combining event-related evoked potentials (ERPs) and China-Wechsler Younger Children Scale (C-WISC) in children with sleep-disordered breathing (SDB) with vs. without OSA. METHODS: This was a retrospective case-control study of all consecutive children (n = 148) with adenoid tonsil hypertrophy between July 2017 and March 2019 at the Hospital. RESULTS: The children were divided into the OSA (n = 102) and non-OSA (n = 46) groups. The apnea-hypopnea index (AHI), obstructive apnea index (OAI), and obstructive apnea-hypopnea index (OAHI) in the OSA group were elevated compared with those of the non-OSA group (all P < 0.001). The mean oxygen saturation (SaO2) and SaO2 nadir were lower in the OSA group compared with the non-OSA group (both P < 0.001). The respiratory arousal index (RAI) values in the OSA group were larger than those of the non-OSA group (P < 0.001). The P300 and N100 latencies in the OSA group were longer than those of the non-OSA group (both P < 0.001). Pearson's correlation analysis revealed correlations of the P300 peak latency with full-scale intelligence quotient (FIQ) (P < 0.001 and r = -0.527), verbal intelligence quotient (VIQ) (P < 0.001 and r = -0.448), and performance intelligence quotient (PIQ) (P < 0.001 and r = -0.515). There was a correlation between the N100 peak latency and PIQ (P = 0.026 and r = -0.183). CONCLUSION: ERPs, as an objective measurement, might help assess cognitive impairment in children with OSA.

Aberrant methylation­mediated decrease of lncRNA HNF1A­AS1 contributes to malignant progression of laryngeal squamous cell carcinoma via EMT.

Aberrant methylation is one of the most frequent epigenetic alterations that regulate the expression levels of genes, including long non­coding RNAs (lncRNAs), in tumors. However, to the best of our knowledge, the expression and function of hepatic nuclear factor 1α antisense RNA 1 (HNF1A­AS1) and its methylation condition have not yet been reported in the development and progression of laryngeal squamous cell carcinoma (LSCC). In the present study, the expression and methylation of HNF1A­AS1 were first examined by reverse transcription­quantitative PCR, bisulfite genomic sequencing and methylation­specific polymerase chain reaction in samples from patients with LSCC, which were based on the in silico analysis using The Cancer Genome Atlas data, and were then further verified in LSCC cell lines with and without 5­Aza­2'­deoxycytidine (5­Aza­dC) treatment. Subsequently, proliferation, cell cycle distribution, migration and invasion of LSCC cells following either knockdown or overexpression of HNF1A­AS1 were determined in vitro. Furthermore, the characteristic of HNF1A­AS1 on epithelial­mesenchymal transition (EMT) changes was investigated in vitro and in vivo. The associations between the expression levels of HNF1A­AS1 and tumorigenicity and cervical lymph node metastasis were assessed in a xenograft model in nude mice. In the present study, downregulation and hypermethylation in CpG sites of HNF1A­AS1 were detected in LSCC tissues as well as metastatic cervical lymph nodes samples when compared with those in the adjacent non­tumor tissues. Additionally, HNF1A­AS1 inhibited proliferation, migration and invasion of LSCC cells in vitro by regulating the process of EMT. Furthermore, HNF1A­AS1 inhibited tumor growth and metastasis by regulating EMT in vivo. Additionally, the migration and invasion abilities, and the expression levels of HNF1A­AS1 and EMT markers in LSCC cells were significantly reversed by treatment with 5­Aza­dC. In summary, HNF1A­AS1 was downregulated by hypermethylation in LSCC and laryngeal cancer cells. These findings suggested that HNF1A­AS1 could serve as a tumor suppressor lncRNA in LSCC by regulating the EMT process, leading to the discovery of novel therapeutic targets and strategies for the treatment of patients with LSCC.

[Analysis of influencing factors of excessive daytime sleepiness in adults with different degrees of sleep-disordered breathing].

Objective:To explore the main influencing factors of excessive daytime sleepiness（EDS） in adults with different degrees of sleep-disordered breathing（SDB）, which will provide the scientific evidences for the individualized diagnosis and treatment. Method:Retrospective analysis was performed on the clinical data of 361 young and middle-aged snoring patients monitored by polysomnography. According to the presence or absence of obstructive sleep apnea（OSA） and apnea hypopnea index（AHI） levels, they were divided into primary snoring（AHI<5）, mild OSA（AHI 5-<15）, moderate OSA（AHI 15-<30） and severe OSA（AHI≥30）. From sleep efficiency（ES）, different sleep stages（REM, NREM1, NREM2, NREM3） ratio of total sleep, oxygen reduction index（ODI）, blood oxygen saturation<90% of total sleep time（TS90%）, the average saturation of blood oxygen（MSaO2） and the lowest blood oxygen saturation（LSaO2） of all-night sleep, and AHI in different sleep stages（REM-AHI, NREM-AHI）, MSaO2 in different sleep stages（REM-MSaO2, NREM-MSaO2） and LSaO2 in different sleep stages（REM-LSaO2, NREM-LSaO2）, the main influencing factors of EDS were discussed. Result:Among the 361 patients, 23 patients suffered from the primary snoring, 47 patients with mild OSA, 56 patients with moderate OSA, and 235 patients with severe OSA. REM-AHI, ODI and TS90% in EDS group were 10.9, 9.6 and 0.2 respectively in patients with primary snoring, which were significantly higher than those without EDS（P<0.01）. The main influencing factors of EDS were REM-AHI, ODI, and TS90%. However, among patients with mild OSA, REM-AHI was the main influencing factor of EDS, REM-AHI of the EDS group was 29.6, which was significantly higher than that of the non-EDS（P<0.05）. In patients with moderate OSA, LSaO2 of the EDS group was 76.2, significantly lower than the group without EDS（P<0.05）, the main influencing factor of EDS is LSaO2. In patients with severe OSA, BMI, ODI and TS90% in EDS group were significantly higher than those without EDS（P<0.05 or P<0.01）, while NREM-MSaO2, MSaO2 and LSaO2 were significantly lower than those without EDS（P<0.05 or P<0.01）. The main influencing factors of EDS were BMI, NREM-MSaO2, MSaO2, LSaO2, ODI and TS90%. Conclusion:Frequent apnea during REM stage may be one of the important factors causing EDS in patients with primary snoring and mild OSA. For patients with moderate and severe OSA, intermittent hypoxia at night may be the main factor leading to EDS, and obesity may promote the development of the disease and the occurrence of sleepiness.

[Effect of tympanoplasty on wet ear with different mucosal status of tympanic cavity].

Objective:A retrospective analysis of audiologic outcome and graft take rate on post-tympanoplasty with different middle ear mucosal conditions in wet ear. Method:According to the characteristics of middle ear mucosal condition and residual eardrum, 80 cases with wet ear of chronic suppurative otitis media were divided into the hydrocele group, the swelling group and the granulation group. The factors in different groups, including gender, age, disease course, sides, size and location of perforations, destruction of ossicular chain and reconstruction methods were analyzed. Moreover, postoperative hearing improvement and graft take rate were compared among the three groups. Result:There was no significant difference in gender, age, disease course, sides, size and location of perforations among the hydrocele group, the swelling group and the granulation group （P>0.05）. Overall, the postoperative average Air-Bone Gaps（ABG） were reduced in all wet ear patients after surgery （P<0.01）. The ABG was decreased from （25.5 ± 10.8） dB to（15.4 ± 9.4） dB in the hydrocele group, and decreased from （27.6 ± 8.7） dB to （15.2 ± 9.6） dB in the swelling group, and from （29.5 ± 7.7） dB to （17.2 ± 17.2） dB in the granulation group. The graft take rates were 90.0% in totally. There were no significant difference in graft take rates among the three groups, and 84.6% in the hydrocele group, 93.3% in the swelling group and 100.0% in the swelling group（P>0.05）. Conclusion:Wet ear is not an absolute contraindication of tympanoplasty for chronic suppurative otitis media. Whether there was effusion, swelling or granulomatous hyperplasia in the tympanoplasty, the patients'hearing improved significantly after tympanoplasty, and the healing rate of the tympanoplasty did not decrease. Further basic and clinical studies are needed to standardize the timing of wet ear surgery, clarify the operative contraindication and elucidate the pathophysiological mechanism of eardrum healing.

Related biomarkers of neurocognitive impairment in children with obstructive sleep apnea.

OBJECTIVES: Different experiment approaches have demonstrated that children with obstructive sleep apnea (OSA) exhibit neurocognitive and behavioral deficits. This review summarized the potential biomarkers of OSA-associated neurocognitive impairment in children. METHODS: A scoping review of studies on children with OSA that evaluated the potential value of different markers in identifying neurocognitive impairment was undertaken. Additionally, the biomarkers were categorized according to the different research methods, including brain imaging studies, serological indicators and urine markers. RESULTS: Majority of the studies that evaluated blood biomarkers, plasma insulin growth factor-1 (IGF-1) and Alzheimer's disease (AD)-related biomarkers appeared to exhibit a favorable profile, and could discriminate between OSA children with or without neurocognitive impairments. Brain imaging studies and urinary neurotransmitters could also be helpful for screening OSA cognitive morbidity in children. CONCLUSION: Due to limited research methods available in children, the cognitive susceptibility of children with OSA has been rarely studied. The main reason for this may be the limited research methods in children. Numerous study populations of children and complex psychological tests are required, which involve major labor and costs.Multi-center prospective studies are needed to identify suitable biomarkers for the timely prediction and effective intervention to prevent neurocognitive impairment in children with OSA and to explore further opportunities in this arena.

[Diagnosis and treatment of unilateral allergic fungal sinusitis].

OBJECTIVE: To investigate the clinical and pathological manifestation, prognosis of unilateral allergic fungal sinusitis (AFS), and to analyze the characters and treatment paradigm of unilateral AFS. METHOD: Clinical and pathological information of 10 cases of unilateral AFS were analyzed. Nasal endoscopy, skin prick test, and visual analogue score (VAS) of severity of illness were taken before surgery. Mucosa membrane and inspissated secretion obtained during endoscopic surgery were stained with hematoxylin-eosin and silver hexosamine. Regular clean of sinus and intranasal steroid spray were taken after surgery. RESULT: Endoscopy showed that 5 cases had pale mucous membranes in the ipsilateral nasal cavity. Skin prick test was positive in all patients. Nasal CT scan demonstrated unilateral lesion in all 10 patients. In the involved sinus, all 10 patients had brown or yellow brown viscous secretion, which demonstrated eosinophilic amorphous mass with accumulation of eosinophils, Charcot-Leyden crystallization and fungal hyphae under microscope. The number of eosinophils in lamina propria of sinus mucosa membrane was 72 +/- 11/hpf. After follow-up for 16 to 26 months(mean 22 months), 9 cases were cured and 1 improved. The pre-operative VAS was 8.5 +/- 1.2, and the post-operative VAS was 1.1 +/- 1.0 (P < 0.01). CONCLUSION: The systemic and local allergic reaction may co-exist in unilateral AFS, in which local hypersensitivity may be the dominant reaction. Endoscopic sinus surgery and intranasal steroid spray are effective in the treatment of unilateral AFS.

Tissue-protective effect of glutamine on hepatic ischemia-reperfusion injury via induction of heme oxygenase-1.

BACKGROUND/AIMS: Glutamine showed cytoprotective activity in vitro on anoxia-reoxygenation injury via induction of heme oxygenase-1 (HO-1). We thus investigated its in vivo tissue-protective effect in a rat liver ischemia-reperfusion (I/R) model. METHODS: Before the I/R procedure, animals were treated with glutamine. Liver injury was evaluated by serum liver enzymes, histological examination and apoptosis detection by transferase-mediated uridine nick end labeling staining. Meanwhile, expression and activities of HO-1 were measured by Western blot and a biochemical method. Liver blood flow was measured by using a laser Doppler flowmeter, and oxidative injury was investigated by the thiobarbituric acid-reactive substance (TBARS) assay. The inflammatory cytokine monocyte chemotactic protein (MCP)-1 was quantified by ELISA. RESULTS: I/R caused a large increase in levels of liver enzymes, remarkably inducing the necrosis and apoptosis of liver tissue, which was markedly inhibited by glutamine, during which HO-1 was upregulated significantly, and the HO-1 inhibitor zinc protoporphyrin nullified the effect of glutamine. Liver blood flow was greatly reduced after I/R; however, it was significantly improved by glutamine. Lipid peroxidation (TBARS) in liver tissue was largely induced which was significantly lowered by glutamine. Similar results were also observed for the production of MCP-1. CONCLUSION: Glutamine protected tissue against oxidative injury during rat hepatic I/R, by induction of HO-1 to fulfill antioxidative and antiapoptotic effects.

Pretreatment with glutamine attenuates anoxia/reoxygenation injury of human proximal renal tubular epithelial cells via induction of heme oxygenase-1.

BACKGROUND/AIMS: Glutamine showed potential cytoprotective activity probably due to induction of heme oxygenase-1 (HO-1). We thus investigated the effect of glutamine in vitro on anoxia/reoxygenation (A/R) injury of renal tubular epithelial cells. METHODS: Human proximal renal tubular epithelial cells (HK-2) were subjected to A/R with or without glutamine, after which viability and apoptosis of the cells were determined by MTT assay and annexin V flow cytometry, respectively. Meanwhile, expression of HO-1, caspase-3, Bcl-2 and inducible nitric oxide synthetase (iNOS) was measured by reverse transcriptase polymerase chain reaction and Western blot. RESULTS: A/R significantly induced apoptosis of HK-2 cells, which was inhibited by glutamine, during which HO-1 was upregulated significantly, but nullified by p38MAPK inhibitor. Caspase-3 and iNOS increased after A/R; however, glutamine inhibited this potential. Opposite results were observed for Bcl-2. CONCLUSION: Glutamine prevents A/R injury of HK-2 cells through induction of HO-1 via a p38MAPK-dependent pathway, which plays a key role in the cytoprotective effect of glutamine.