Flupentixol/melitracen for chronic refractory cough after treatment failure with other neuromodulators.

BACKGROUND: Gabapentin and baclofen are recommended for the treatment of chronic refractory cough (CRC). We investigated the efficacy of flupentixol/melitracen in patients unresponsive to these neuromodulators.METHODS: A total of 101 patients with CRC who failed to respond to gabapentin and baclofen were recruited, and treated with flupentixol/melitracen. The prevalence of cough resolution and changes in the Cough Symptom Score (CSS), cough thresholds to capsaicin, Hull Airway Reflux Questionnaire (HARQ), Leicester Cough Questionnaire (LCQ), Generalized Anxiety Disorder-7, Hamilton Anxiety Rating Scale, Patient Health Questionnaire-9, and Hamilton Depression Rating Scale-24 were evaluated after treatment.RESULTS: Ninety-eight patients (97.0%) completed the study. The overall successful cough resolution rate was 62.4% (63/101). Cough resolution was accompanied by an obvious decrease in the CSS and HARQ score and a remarkable increase in cough thresholds to capsaicin challenge and LCQ score, whereas anxiety and depression scores did not change significantly. The prevalence of adverse effects (e.g., insomnia and dizziness) was 21.8%. The prevalence of cough recurrence within 2 weeks after treatment cessation was 17.8%.CONCLUSION: Flupentixol/melitracen may be an efficacious option for CRC unresponsive to other neuromodulators.

Novel lncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting miR-29b.

Transforming growth factor-ß/Smad signaling plays an important role in diabetic nephropathy. The current study identified a novel Smad3-dependent long noncoding RNA (lncRNA) Erbb4-IR in the development of type 2 diabetic nephropathy (T2DN) in db/db mice. We found that Erbb4-IR was highly expressed in T2DN of db/db mice and specifically induced by advanced glycosylation end products (AGEs) via a Smad3-dependent mechanism. The functional role of Erbb4-IR in T2DN was revealed by kidney-specific silencing of Erbb4-IR to protect against the development of T2DN, such as elevated microalbuminuria, serum creatinine, and progressive renal fibrosis in db/db mice, and to block AGE-induced collagen I and IV expression in mouse mesangial cells (mMCs) and mouse tubular epithelial cells (mTECs). Mechanistically, we identified that the Erbb4-IR-microRNA (miR)-29b axis was a key mechanism of T2DN because Erbb4-IR was able to bind the 3' untranslated region of miR-29b genomic sequence to suppress miR-29b expression at transcriptional level. In contrast, silencing of renal Erbb4-IR increased miR-29b and therefore protected the kidney from progressive renal injury in db/db mice and prevented mTECs and mMCs from AGE-induced loss of miR-29b and fibrotic response in vitro. Collectively, we identify that Erbb4-IR is a Smad3-dependent lncRNA that promotes renal fibrosis in T2DN by suppressing miR-29b. Targeting Erbb4-IR may represent a novel therapy for T2DN.

Association between interleukin-17 gene polymorphisms and the risk of laryngeal cancer in a Chinese population.

IL-17 is associated with the occurrence and development of laryngeal cancer. However, no study has reported the association between IL-17 polymorphisms and laryngeal cancer susceptibility. Therefore, we analyzed the association of three polymorphism loci (rs2275913, 197 G/A; rs3748067, 383 A/G; and rs763780, 7488 T/C) of IL-17A and IL-17F with laryngeal cancer in the Chinese population. A case-control study was performed with 325 patients and 325 controls. Polymorphisms were detected by polymerase chain reaction and sequencing methods. SPSS17.0 software was used for statistical analysis. Allele and genotype frequencies of IL-17A rs2275913 were significantly different between patients and controls (P < 0.05). Frequencies of rs2275913 (197 G/A) AA and GA+AA genotypes compared to the GG genotype were significantly higher in patients than in controls, indicating the association of these genes with laryngeal cancer susceptibility; adjusted OR values were 2.54 (1.50-4.23) and 1.62 (1.19-2.17), respectively. Furthermore, individuals with the GA+AA genotype, compared to the GG genotype, aged ≤60 years, with smoking and alcohol consumption habits, and without a family history of cancer showed a higher cancer risk (OR = 2.74, 95%CI = 1.41-5.23; OR = 2.11, 95%CI = 1.21-3.55; OR = 1.91, 95%CI = 1.02-3.70; OR = 1.99, 95%CI = 1.08-3.39, respectively). In conclusion, the rs2275913 IL-17A (197 G/A) is associated with the incidence and development of laryngeal cancer in the Chinese population, and the AA and GA+AA genotypes harbor a high laryngeal cancer risk.

[Analysis of tinnitus with sudden deafness].

Objective:To explore the pathogenesis of tinnitus.Method:Retrospective analysis of 192 patients with sudden deafness was done with the characteristics.Charactier of tinnitus and the factors that may affect tinnitus.Result:The intense of tinnitus is related with sex,χ²=14.704,P<0.01,and with age increased,the difference was more significant.The intense of tinnitus has not significant difference between age group with 45 years old(χ² =6.515,P>0.05) and the classification of sudden deafness and the degree of hearing loss(χ²=7.783,P>0.05,χ²=17.374,P>0.05).Conclusion:Tinnitus was the protection mechanism of the body,and the intensity was irrelevant to hearing loss.On one hand,there may be different modulate systems between different individual,on the other hand,women over 45 years old were more suffered from the severe tinnitus.

Fas-associated factor 1 plays a negative regulatory role in the antibacterial immunity of Locusta migratoria.

Insect immune responses are precisely regulated to maintain immune balance. In this study, the Fas-associated factor 1 (FAF1) gene of Locusta migratoria manilensis, a homologue of the caspar gene that functions as a specific negative regulator in the antibacterial immunity pathway, was cloned. Gene expression analysis showed that FAF1 was expressed throughout the developmental stages and in all tested tissues, but its transcription levels varied significantly. Thus, FAF1 appears to be tightly regulated and is probably involved in multiple physiological processes. In addition, the antimicrobial peptide gene prolixicin was cloned and characterized. After bacterial challenge, prolixicin was rapidly up-regulated, whereas FAF1 was markedly down-regulated. This result was consistent with the observation that prolixicin was hyperactivated when FAF1 was suppressed by RNA interference. Moreover, after bacterial infection, the survival rate of FAF1-knockdown locusts was much higher than that of the wild-type. Taken together, these findings strongly suggest that FAF1 shares a similar function as caspar in Drosophila and may be involved in the negative regulation of antibacterial immunity in locusts.

Controllable growth of highly ordered ZnO nanorod arrays via inverted self-assembled monolayer template.

This article presents a facile and effective approach to the controllable growth of highly ordered and vertically aligned ZnO nanorod arrays on the GaN substrate via a hydrothermal route by using the TiO(2) ring template deriving from the polystyrene microsphere self-assembled monolayer. The size of TiO(2) ring template can be flexibly tuned from 50 to 400 nm for the 500 nm polystyrene microspheres by varying the time of reactive ion etching and the concentration of TiO(2) sol. As a result, the diameter of the individual ZnO nanorods can be potentially tuned over a wide range. The combination of several characterization techniques has demonstrated that the ordered ZnO nanorods are highly uniform in diameter and height with perfect alignment and are epitaxially grown along [0001] direction. This work provides a novel and accessible route to prepare oriented and aligned ZnO nanorod arrays with high crystalline quality.

Microstructures and mechanical properties of silks of silkworm and honeybee.

Natural silks as important biomaterials have wide applications in scaffolds for tissues, biocompatible coatings and drug delivery, etc. In this paper, we report on the microstructures and mechanical properties of honeybee and silkworm silks. The microstructures and mechanical properties of these natural silks are measured by environment scanning electron microscopy (ESEM), scanning probe microscopy (SPM), tensile tests, and nanoindentation. It is found that the honeybee silk appears as a single fiber with a circular cross-section and has a much finer and smoother texture than the silkworm silk. The honeybee silk exhibits a distinct linear and brittle elastic feature with an elastic modulus of 6.5GPa and a breaking strain of 3.8%, whereas the silkworm silk possesses a nonlinear and hierarchical failure character with an initial elastic modulus of 8.9GPa and a breaking strain of 15.7%. Moreover, the nanoindentation measurements show that the honeybee silk exhibits much less anisotropy than the silkworm silk. The ratio of the longitudinal modulus to the transverse modulus of the honeybee silk is 2.0, whereas that of the silkworm silk is 18.9. The different structural and mechanical properties of the honeybee and silkworm silks are likely a result of their specific biological functions.

[Distribution of calcitonin gene-related peptide-like immunoreactive fibres in the temporomandibular joint of rat].

OBJECTIVE: To observe the distribution of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerve fibres in rat's temporomandibular joint (TMJ). METHODS: The avidin-biotin-peroxidase complex method and image analysis were employed to detect CGRP-LI nerve fibres in frozen sections of TMJs in eight rats. RESULTS: CGRP-LI nerve fibres were plentifully distributed in TMJs except the central disc band and bone, mainly in the periphery of blood vessels, especially arteries. Density: anterior disc attachment and capsule, (454.6 +/- 72.8) mm(2); posterior portion, (302.7 +/- 43.4) mm(2); lateral portion, (240.2 +/- 23.6) mm(2); medial portion, (229.6 +/- 25.0)mm(2); and peripheral portion of disc, (202.4 +/- 35.2) mm(2). CONCLUSION: CGRP-LI nerve fibres were widely distributed in rat TMJ and were a part of trigeminal sensory nerve. Density was highest in anterior disc attachment and capsule.

Estimation of PC12 cell numbers with acid phosphatase assay and mitochondrial dehydrogenase assay: dopamine interferes with assay based on tetrazolium.

Both the acid-phosphatase and mitochondrial dehydrogenase assay have been used to quantify cell numbers. The commonly used acid-phosphatase assay uses p-nitrophenyl phosphate as a substrate, while the mitochondrial dehydrogenase assay is based on the conversion of tetrazolium to formazan. Our experimental results showed that the former assay was more sensitive in detecting small numbers of PC12 cells (200-10,000 cells/well), whereas the latter was useful for larger numbers of cells (2000-40,000 cells/well). The number of PC12 cells decreased after dopamine treatment, according to the acid-phosphatase assay and by direct cell counts under a light microscope. However, the optical densities measured by the mitochondrial dehydrogenase assay increased after dopamine treatment. We tried to clarify discrepancies between the two assays, since dopamine is an important neurotransmitter and both assays are commonly used to estimate cell numbers. To elucidate the interference between dopamine and tetrazolium salt, cell-free control experiments were performed. Dopamine and other catecholamines (adrenaline and noradrenaline) reacted with tetrazolium and, thus, produced a false positive reaction in the assay. We therefore conclude that the tetrazolium assay is not a suitable method for evaluating the number of catecholamine-treated cells, while the acid-phosphatase assay is reliable and sensitive.

The SH2-SH2-SH3 domain of phospholipase C-gamma1 directly binds to translational elongation factor-1alpha.

Phospholipase C-gamma1 (PLC-gamma1) is a lipase that hydrolyzes PIP2 to generate two second messengers, IP3 and DAG. By using the yeast two-hybrid system, we identified the translational elongation factor-1alpha (EF-1alpha) as a binding protein of PLC-gamma1 from the human B-lymphocyte library. Direct interaction between EF-1alpha and PLC-gamma1 was confirmed by the in vitro binding experiment using purified PLC-gamma1. Furthermore, from the in vitro binding experiment, we could demonstrate that the carboxyl terminal region of EF-1alpha is involved in the interaction with PLC-gamma1, and that both SH2 and SH3 domains of PLC-gamma1 are required for the interaction with EF-1alpha. In vivo interaction between EF-1alpha and PLC-gamma1 was confirmed by the immunoprecipitation experiment using anti-EF-1alpha antibody. The interaction between EF-1alpha and PLC-gamma1 was enhanced by EGF-treatment. Taken together, we suggest that EF-1alpha might play a role in PLC-gamma1-mediated signal transduction.

Glutathione protects PC12 cells from ascorbate- and dopamine-induced apoptosis.

The role of reduced glutathione (GSH) on ascorbate- and dopamine-induced apoptosis in PC12 cells was investigated. Ascorbate is a potent reducing agent and is thus expected to protect against dopamine-induced apoptosis. However, we found that both ascorbate and dopamine killed PC12 cells and ascorbate enhanced dopamine-induced toxicity. The EC50 of cell toxicity induced by ascorbate, dopamine and dopamine plus 0.1 mM ascorbate during 24-h treatment were 0.93+/-0.15 mM, 0.18+/-0.05 mM and 0.13+/-0.04 mM, respectively. When the medium contained 10 mM GSH, the EC50 increased approximately three- and sevenfold for ascorbate and dopamine, respectively. With increased treatment duration, no further toxic effects of ascorbate or dopamine were observed. The GSH synthesis inhibitor, DL-buthionine-(S,R)-sulfoximine (BSO), induced cell toxicity and potentiated the toxic effects of ascorbate and dopamine, suggesting that endogenous GSH participates in protecting against basal oxidative stress. We conclude that both ascorbate and dopamine induce apoptosis in PC12 cells and further that GSH protects them from apoptosis. This study indicates that the toxic effects of ascorbate are potentially due to an oxidative mechanism, similar to that induced by dopamine.

Dopamine requires ascorbic acid to be the prolactin release-inhibiting factor.

A high concentration of dopamine (10(-6) mol/l) inhibited prolactin release for < 60 min during a 2-h perifusion period by use of primary cultured pituitary cells. However, when dopamine (10(-6) mol/l) and control medium were alternately perifused, dopamine inhibited prolactin release for a longer period, indicating that the inability of dopamine to sustain an inhibitory action is likely caused by decreased sensitivity of the lactotrophs to dopamine. When 3 x 10(-7) mol/l dopamine was perifused, prolactin release was inhibited for only 15 min, and the rate of prolactin release was decreased to a nadir by addition of ascorbic acid (10(-4) mol/l) 15 min after the start of dopamine perifusion. Dopamine decreased density of dopamine D2 receptors, and ascorbic acid inhibited the receptor downregulation in GH4ZR7 cells. These results support our hypothesis that dopamine requires a supplementary agent to be the prolactin release-inhibiting factor and that the supplementary agent is ascorbic acid.

[Effects of different lowdoses of aspirin on platelet activation and the number of platelets in the patients with coronary heart disease].

The number of alpha-granule membrane protein 140 (GMP-140) molecules was detected by using specific monoclonal antibodies (125I-SZ-51) against GMP-140 in three groups of patients with unstable angina treated with aspirin 50 mg (n = 27), 150 mg (n = 26) and 300 mg (n = 30) a day before and 7 days after treatment. The number of platelets was counted by using the routine method. The results indicated that the number of GMP-140 molecules decreased significantly and the number of platelets increased significantly after treatment with aspirin. With the increase of aspirin dosage the degree of these two changes increased (P < 0.01, both) too. When 300 mg of aspirin was used, the number of GMP-140 molecules was lower than that in a control group of healthy subjects (P < 0.005) and the number of platelets reached that of the control group (P > 0.05). There was no difference on the immediate side effects when these three dosages of aspirin were used. The authors of the opinion are that it is rational to use 300 mg of aspirin to treat patients with unstable angina at the beginning.

[Experimental research on treatment of acute organophosphorus insecticides poisoning with high-dose atropine: upregulation of muscarinic receptor].

Acute organophosphorus insecticides poisoning (AOIP) is a common medical emergency. There is, at present, a tendency to use high-dose atropine treatment (HDAT). This study aims to test if, during AOIP, HDAT would cause upregulation of muscarinic receptor (M-R). Male mice of the same batch and strain were raised, randomly divided into 3 groups and orally fed with DDVP of the same dose. HDAT for 7 days was given to group A, HDAT for 36 hours was given to group B and low-dose atropine treatment for 36 hours was given to group C. Then radionuclide assay was employed to measure the M-R in the brain and atrium of the mice in each group. The results were that, compared with a control group, the Bmax values (fmol.mg protein-1) of M-R in groups A and B were increased significantly (P < 0.01), while that in group C showed no evident change (P > 0.05). These results indicate that HDAT leads to some physiological change in the body, which may be responsible for the development of poisoning rebound and atropine dependence.

[Atropine dependence during treatment of acute organophosphorus pesticides poisoning].

In treating patients with acute organophosphorus pesticides poisoning, clinicians pay more attention to poisoning counterattack, while atropine dependence, which resembles counterattack, is not yet fully recognized. The authors analysed 1,039 patients with this kind of poisoning treated in 7 years. Among these cases 157 were dependent on atropine, consisting of 15.1% of the total. The clinical manifestations of the dependence were described. The diagnostic criteria of the dependence and its differential points from counterattack were suggested. It was found that higher occurrence rate of the dependence was seen in patients of younger age, with more severe poisoning and with longer duration and higher total dose of atropine treatment (P < 0.005 respectively). It is considered that its mechanism might be related to increased number of M-receptor and excessive accumulation of acetylcholine. It is suggested that quantitative analysis of relevant receptor be developed.