Myoinositol supplementation in the prevention of gestational diabetes mellitus among high-risk pregnant women: A meta-analysis / Philippine Journal of Obstetrics and Gynecology

Objective@#The objective of the study was to determine the effectiveness of myoinositol (MI) supplementation in the prevention of gestational diabetes mellitus (GDM) among high-risk patients.@*Materials and Methods@#Comprehensive and systemic online searches were performed on PubMed, MEDLINE, Ovid, and Cochrane. Cross-referencing from related articles was also done. Only studies published in English were included in the study. We selected all randomized controlled trials on MI and singleton pregnant women with high risk for GDM.@*Data Collection and Analysis@#Five randomized controlled trials were evaluated by two independent reviewers. For each comparison, the quality of evidence was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Cochrane Collaboration tool. Review Manager 5.3 was used to generate the risk of bias evaluation and the analysis of the results.@*Main Results@#The present study identified five randomized controlled trials involving 871 participants. The comparison of the studies showed a statistically significant reduction in the incidence of GDM in MI supplementation versus the control group (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.19–0.53, P = 0.0001, Z = 4.36) by 68%. Similarly, there is a greater reduction in the incidence of fetal macrosomia among patients in the MI group than the controlled group (OR = 0.24, 95% CI = 0.07–0.78; P = 0.02, Z = 2.36) by 78%. However, there was no difference in terms of incidence of gestational hypertension (OR = 0.61, 95% CI = 0.19–2.01; P = 0.42, Z = −0.81), cesarean section (OR = 0.89, 95% CI = 0.65–1.22; P = 0.47, Z = 0.72), and neonatal hypoglycemia (OR = 0.35, 95% CI = 0.01–8.80; P = 0.53, Z = 0.63) outcomes.@*Conclusion@#MI supplementation taken at 4 g daily would decrease the incidence of GDM and fetal macrosomia. There was no statistically significant reduction in the risk of gestational hypertension, cesarean section, and neonatal hypoglycemia in the supplementation of MI.

Superexpressão do receptor de Inositol 1,4, 5-trifosfato isoforma 3 (ITPR3) em colangiocarcinoma e sua correlação com a proteína dependente de cálcio S100A4 / Inositol 1,4, 5-triphosphate receptor isoform 3 (ITPR3) overexpression in cholangiocarcinoma and its correlation with calcium-dependent protein S100A4

O colangiocarcinoma (CCA) é a segunda neoplasia mais maligna do fígado que surge na árvore biliar. O CCA está associado com mau prognóstico e os principais fatores envolvidos em sua patogênese não são bem compreendidos. Os receptores tirosina quinases (RTKs), como o receptor do fator de crescimento epidérmico (EGFR), podem mediar as vias de sinalização de cálcio intracelular (Ca 2+ ), via inositol 1,4,5-trifosfato (InsP3). Eles ativam os receptores 1,4,5-trifosfato (ITPRs) e regulam o crescimento tumoral. ITPR isoforma 3 é o principal canal de liberação intracelular de Ca 2+ em colangiócitos. Os efeitos do Ca 2+ intracelular, por sua vez são mediados por proteínas de ligação de cálcio, como calmodulina e proteína A4 de ligação de cálcio S100 (S100A4). No entanto, o significado clínico patológico e biológico de EGFR, ITPR3 e S100A4 no CCA permanece obscuro. Assim, o presente trabalho investiga a imuno exprepressão dessas três proteínas em 59 pacientes diagnosticados com CCA, submetidos a tratamento cirúrgico curativo e correlaciona os dados com características clínico-patológicas e sobrevida. A alta expressão de ITPR3 foi correlacionada com os níveis de CA 19-9, estágio TNM e metástases em linfonodos (N). Além disso, a expressão de ITPR3 foi aumentada em CCA distal em comparação com ductos biliares de controle e CCAs intra-hepáticos e peri-hilares. Os escores clínicos ITPR3 e S100A4 foram significativamente correlacionados. Em resumo, a super expressão de ITPR3 pode contribuir para a progressão da CCA e pode representar um potencial alvo terapêutico. Palavras-chave: ITPRs; ITPR3; S100A4; Colangiocarcinoma; Fígado; Câncer

Cholangiocarcinoma (CCA) is the second most malignant neoplasm in the liver that arises from the biliary tree. CCA is associated with a poor prognosis, and the key players involved in its pathogenesis are still not well understood. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), can mediate intracellular calcium (Ca2+) signaling pathways via inositol 1,4,5trisphosphate (InsP3), activating inositol 1,4,5-trisphosphate receptors (ITPRs) and regulating tumor growth. ITPR isoform 3 (ITPR3) is the main intracellular Ca2+ release channel in cholangiocytes. The effects of intracellular Ca2+ are mediated by calciumbinding proteins such as Calmodulin and S100 calcium-binding protein A4 (S100A4). However, the clinicopathological and biological significance of EGFR, ITPR3 and S100A4 in CCA remains unclear. Thus, the present work investigates the immunoexpression of these three proteins in 59 CCAs from patients who underwent curative surgical treatment and correlates the data with clinicopathological features and survival. High ITPR3 expression was correlated with CA 19-9 levels, TNM stage and lymph node metastasis (N). Furthermore, ITPR3 expression was increased in distal CCA compared to control bile ducts and intrahepatic and perihilar CCAs. In summary, ITPR3 overexpression could contribute to CCA progression and it may represent a potential therapeutic target.

IRE1α deficiency impairs autophagy in chondrocytes by upregulating calcium homeostasis endoplasmic reticulum protein / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which inositol-requiring enzyme-1α (IRE1α) regulates autophagy function of chondrocytes through calcium homeostasis endoplasmic reticulum protein (CHERP).@*METHODS@#Cultured human chondrocytes (C28/I2 cells) were treated with tunicamycin, 4μ8c, rapamycin, or both 4μ8c and rapamycin, and the expressions of endoplasmic reticulum (ER) stress- and autophagy-related proteins were detected with Western blotting. Primary chondrocytes from ERN1 knockout (ERN1 CKO) mice and wild-type mice were examined for ATG5 and ATG7 mRNA expressions, IRE1α and p-IRE1α protein expressions, and intracellular calcium ion content using qPCR, Western blotting and flow cytometry. The effect of bafilomycin A1 treatment on LC3 Ⅱ/LC3 Ⅰ ratio in the isolated chondrocytes was assessed with Western blotting. Changes in autophagic flux of the chondrocytes in response to rapamycin treatment were detected using autophagy dual fluorescent virus. The changes in autophagy level in C28/I2 cells overexpressing CHERP and IRE1α were detected using immunofluorescence assay.@*RESULTS@#Tunicamycin treatment significantly up-regulated ER stress-related proteins and LC3 Ⅱ/LC3 Ⅰ ratio and down-regulated the expression of p62 in C28/I2 cells (P < 0.05). Rapamycin obviously up-regulated LC3 Ⅱ/LC3 Ⅰ ratio (P < 0.001) in C28/I2 cells, but this effect was significantly attenuated by co-treatment with 4μ8c (P < 0.05). Compared with the cells from the wild-type mice, the primary chondrocytes from ERN1 knockout mice showed significantly down-regulated mRNA levels of ERN1 (P < 0.01), ATG5 (P < 0.001) and ATG7 (P < 0.001), lowered or even lost expressions of IRE1α and p-IRE1α proteins (PP < 0.01), and increased expression of CHERP (P < 0.05) and intracellular calcium ion content (P < 0.001). Bafilomycin A1 treatment obviously increased LC3 Ⅱ/ LC3 Ⅰ ratio in the chondrocytes from both wild-type and ERN1 knockout mice (P < 0.01 or 0.05), but the increment was more obvious in the wild-type chondrocytes (P < 0.05). Treatment with autophagy dual-fluorescence virus resulted in a significantly greater fluorescence intensity of LC3-GFP in rapamycin-treated ERN1 CKO chondrocytes than in wild-type chondrocytes (P < 0.05). In C28/I2 cells, overexpression of CHERP obviously decreased the fluorescence intensity of LC3, and overexpression of IRE1α enhanced the fluorescence intensity and partially rescued the fluorescence reduction of LC3 caused by CHERP.@*CONCLUSION@#IRE1α deficiency impairs autophagy in chondrocytes by upregulating CHERP and increasing intracellular calcium ion content.

Effects of the ITPR1 gene overexpression on Ca²⁺ concentration, lipid content and calcium transport-related genes in duck uterine epithelial cells / 生物工程学报

Inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is an important intracellular channel for releasing Ca²⁺. In order to investigate the effects of the ITPR1 overexpression on Ca²⁺ concentration and lipid content in duck uterine epithelial cells and its effects on calcium transport-related genes, the structural domain of ITPR1 gene of duck was cloned into an eukaryotic expression vector and transfected into duck uterine epithelial cells. The overexpression of the ITPR1 gene, the concentration of Ca²⁺, the lipid content, and the expression of other 6 calcium transport-related genes was determined. The results showed that the concentration of Ca²⁺ in uterine epithelial cells was significantly reduced after transfection (P<0.05), the triglyceride content was significantly increased (P<0.01), and the high-density lipoprotein content was significantly decreased (P<0.01). The correlation analysis results showed that the overexpression of the C-terminal half of the ITPR1 gene was significantly positively correlated with the total cholesterol content (P<0.01), which was significantly positively correlated with the low-density lipoprotein content (P<0.05). The overexpression of the N-terminal half of the ITPR1 gene was significantly positively correlated with the triglyceride content (P<0.01), which was significantly negatively correlated with the concentration of Ca²⁺ (P<0.05). RT-qPCR results of 6 calcium transport-related genes showed that the overexpression of the C-terminal half of the ITPR1 gene significantly inhibited the expression of the IP3R2, VDAC2 and CAV1 genes, and the overexpression of the N-terminal half of the ITPR1 gene significantly promoted the expression of the IP3R3 and CACNA2D1 genes. In conclusion, the ITPR1 gene overexpression can promote Ca²⁺ release in duck uterus epithelial cells, promote the synthesis of triglyceride, low-density lipoprotein and cholesterol, and inhibit the production of high-density lipoprotein, and the ITPR1 gene overexpression affected the expression of all 6 calcium transport-related genes.

Síndrome dos ovários policísticos: particularidades no manejo da infertilidade / Polycystic ovary syndrome: particularities in the management of infertility

A síndrome dos ovários policísticos (SOP) é responsável por cerca de 80% dos casos de infertilidade anovulatória. Não há na literatura evidências suficientes para a definição do tratamento ideal da infertilidade na SOP, mas repete-se que deve ser iniciado por mudanças no estilo de vida, e frequentemente envolve a indução farmacológica da ovulação e, em casos selecionados, as técnicas de reprodução assistida e o drilling ovariano laparoscópico. Este texto pretende reunir informações atuais sobre o manejo da infertilidade em mulheres com SOP e, dessa forma, permitir ao ginecologista a escolha da melhor abordagem, de forma Individualizada e baseada nas melhores evidências disponíveis.(AU)

Expression of myo-inositol cotransporters in the sciatic nerve and dorsal root ganglia in experimental diabetes

The transport of myo-inositol is the main mechanism for the maintenance of its high intracellular levels. We aimed to measure the mRNA and protein levels of myo-inositol cotransporters in the sciatic nerve (SN) and dorsal root ganglia (DRG) during experimental diabetes. Streptozotocin-induced (STZ; 4, 8, and 12 weeks; 65 mg/kg; ip) diabetic rats (DB) and age-matched euglycemic (E) rats were used for the analysis of mRNA and protein levels of sodium myo-inositol cotransporters 1, 2 (SMIT1, SMIT2) or H+/myo-inositol cotransporter (HMIT). There was a significant reduction in the mRNA levels for SMIT1 in the SN and DRG (by 36.9 and 31.0%) in the 4-week DB (DB4) group compared to the E group. SMIT2 was not expressed in SN. The mRNA level for SMIT2 was up-regulated only in the DRG in the DB4 group. On the other hand, the protein level of SMIT1 decreased by 42.5, 41.3, and 44.8% in the SN after 4, 8, and 12 weeks of diabetes, respectively. In addition, there was a decrease of 64.3 and 58.0% of HMIT in membrane and cytosolic fractions, respectively, in the SN of the DB4 group. In the DRG, there was an increase of 230 and 86.3% for SMIT1 and HMIT, respectively, in the DB12 group. The levels of the main inositol transporters, SMIT1 and HMIT, were greatly reduced in the SN but not in the DRG. SMIT-1 was selectively reduced in the sciatic nerve during experimental STZ-induced diabetes.

Efficacy and safety of sitagliptin added to metformin and insulin compared with voglibose in patients with newly diagnosed type 2 diabetes

OBJECTIVE: To assess the efficacy and safety of sitagliptin compared with voglibose added to combined metformin and insulin in patients with newly diagnosed type 2 diabetes (T2DM). METHODS: In this 12-week prospective, randomized, parallel trial, 70 newly diagnosed T2DM patients with glycosylated hemoglobin (HbA1c) ≥9% and/or fasting plasma glucose (FPG) ≥11.1 mmol/L were randomized (1:1) to receive sitagliptin 100 mg per day + metformin + insulin glargine or voglibose 0.2 mg three times daily + metformin + insulin glargine. Change in HbA1c at week 12 was the primary endpoint. RESULTS: The mean baseline HbA1c was 11.0% in the patients. The changes in HbA1c from baseline were -6.00% in the sitagliptin group and -3.58% in the voglibose group, and the between-group difference was -2.42% (95% CI -1.91 to -2.93, p=0.02). The differences in FPG and homeostatic model assessment of β-cell function (HOMA-β) and the change in body weight between groups from baseline were -2.95 mmol/L (p=0.04), 43.91 (p=0.01) and -2.23 kg (p=0.01), respectively. One patient (2.9%) in the sitagliptin group and three patients (8.6%) in the voglibose group exhibited hypoglycemia. CONCLUSIONS: Sitagliptin added to combined metformin and insulin therapy showed greater efficacy and good safety regarding hypoglycemia in patients with newly diagnosed T2DM compared with voglibose.

Pharmacological Therapy in Panic Disorder: Current Guidelines and Novel Drugs Discovery for Treatment-resistant Patient

Panic disorder (PD) being one of the most intensively investigated anxiety disorders is considered a heterogeneous psychiatric disease which has difficulties with early diagnosis. The disorder is recurrent and usually associated with low remission rates and high rates of relapse which may exacerbated social and quality of life, causes unnecessary cost and increased risk for complication and suicide. Current pharmacotherapy for PD are available but these drugs have slow therapeutic onset, several side effects and most patients do not fully respond to these standard pharmacological treatments. Ongoing investigations indicate the need for new and promising agents for the treatment of PD. This article will cover the importance of immediate and proper treatment, the gap in the current management of PD with special emphasis on pharmacotherapy, and evidence regarding the novel anti-panic drugs including the drugs in developments such as metabotropic glutamate (mGlu 2/3) agonist and levetiracetam. Preliminary results suggest the anti-panic properties and the efficacy of duloxetine, reboxetine, mirtazapine, nefazodone, risperidone and inositol as a monotherapy drug. Apart for their effectiveness, the aforementioned compounds were generally well tolerated compared to the standard available pharmacotherapy drugs, indicating their potential therapeutic usefulness for ambivalent and hypervigilance patient. Further strong clinical trials will provide an ample support to these novel compounds as an alternative monotherapy for PD treatment-resistant patient.

Identification of phospholipase C β downstream effect on transient receptor potential canonical 1/4, transient receptor potential canonical 1/5 channels

Gα(q)-coupled receptor stimulation was implied in the activation process of transient receptor potential canonical (TRPC)1/4 and TRPC1/5 heterotetrameric channels. The inactivation occurs due to phosphatidylinositol 4,5-biphosphate (PI(4,5)P₂) depletion. When PI(4,5)P₂ depletion was induced by muscarinic stimulation or inositol polyphosphate 5-phosphatase (Inp54p), however, the inactivation by muscarinic stimulation was greater compared to that by Inp54p. The aim of this study was to investigate the complete inactivation mechanism of the heteromeric channels upon Gα(q)-phospholipase C β (Gα(q)-PLCβ) activation. We evaluated the activity of heteromeric channels with electrophysiological recording in HEK293 cells expressing TRPC channels. TRPC1/4 and TRPC1/5 heteromers undergo further inhibition in PLCβ activation and calcium/protein kinase C (PKC) signaling. Nevertheless, the key factors differ. For TRPC1/4, the inactivation process was facilitated by Ca²⁺ release from the endoplasmic reticulum, and for TRPC1/5, activation of PKC was concerned mostly. We conclude that the subsequent increase in cytoplasmic Ca²⁺ due to Ca²⁺ release from the endoplasmic reticulum and activation of PKC resulted in a second phase of channel inhibition following PI(4,5)P₂ depletion.

Evaluation of Transcranial Magnetic Stimulation Efficiency in Major Depressive Disorder Patients: A Magnetic Resonance Spectroscopy Study

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD). This study evaluated the antidepressant effect of rTMS and examined how it affected N-asetyl aspartate (NAA), choline (Cho), creatine (Cr), lactate (Lac), myoinositol (mIns), glutamate (Glu), glutathione (GSH), and glutamine (Gln) metabolite levels in the left dorsolateral prefrontal cortex (DLPFC) of MDD patients who were not receiving antidepressant medication. METHODS: In total, 18 patients (10 female, 8 male) were evaluated. Each patient underwent H magnetic resonance spectroscopy (H-MRS) before and within 3 days of completion of TMS therapy. All patients completed 20 sessions of rTMS directed at the left DLPFC over a 2-week period. The Hamilton Depression Scale (HAMD) scores of patients were calculated, and their responses to treatment were assessed within 1–3 days of completion of TMS. RESULTS: We found statistically significant differences in HAMD scores before and after rTMS. Moreover, the peak metabolite ratios of NAA/Cr, GSH/Cr, and Gln/Cr were significantly higher after rTMS compared to those before rTMS. CONCLUSION: Increased understanding of the mechanism of action of TMS will improve its application and may stimulate development of new-generation therapeutic agents.

Endoplasmic Reticulum Stress Induces MUC5AC and MUC5B Expression in Human Nasal Airway Epithelial Cells

OBJECTIVES: Endoplasmic reticulum (ER) stress is known to be associated with inflammatory airway diseases, and three major transmembrane receptors: double-stranded RNA-activated protein kinase-like ER kinase, inositol requiring enzyme 1, and activating transcription factor 6 (ATF6) play important roles in ER stress-related proinflammatory signaling. However, the effects of ER stress and these three major signaling pathways on the regulation of the production of airway mucins in human nasal airway epithelial cells have not been elucidated. METHODS: In primary human nasal epithelial cells, the effect of tunicamycin (an ER stress inducer) and 4-phenylbutyric acid (4-PBA, ER stress inhibitor) on the expression of MUC5AC and MUC5B was investigated by reverse transcriptasepolymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis. Small interfering RNA (siRNA) transfection was used to identify the mechanisms involved. RESULTS: Tunicamycin increased the expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules, including spliced X-box binding protein 1 (XBP-1), transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP), and ATF6. In addition, 4-PBA attenuated the tunicamycin-induced expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules. Furthermore, siRNA knockdowns of XBP-1, CHOP, and ATF6 blocked the tunicamycin-induced mRNA expressions and glycoprotein productions of MUC5AC and MUC5B. CONCLUSION.: These results demonstrate that ER stress plays an important role in the regulation of MUC5AC and MUC5B via the activations of XBP-1, CHOP, and ATF6 in human nasal airway epithelial cells.

Evaluation of the effect of retrograde intrarenal surgery with myo-inositol oxygenase

Objective: To investigate the effect of retrograde intra-renal surgery [RIRS] on kidneys using the myoinositol oxygenase [MIOX] enzyme. MIOX is a renal tubular-specific novel marker for the early diagnosis of acute kidney injury

Methods: A total of twenty seven individuals that had undergone RIRS to treat kidney stones were included in the study. Biochemical tests were performed on serum samples collected immediately before RIRS [hour 0] and at the 6th and 24th hours after the surgery

Results: The creatinine value at hour 6 was lower than the baseline [hour 0] value [p = 0.0305]. Cystatin C at hour 6 was lower than the value measured at hour 24 [p = 0.0142]. Similarly, MIOX was lower at hour 6 compared to hour 24 [p = 0.0214]. MIOX/creatinine at hour 6 was lower than the value calculated at hour 24 [p = 0.0348]. The basal values of MIOX and creatinine were found to have a positive correlation [correlation coefficient r = 0.5946, p = 0.0035]

Conclusions: Similar to the serum creatinine, the serum MIOX level provides information about kidney functions. RIRS was confirmed to be a safe procedure for the treatment of acute kidney injury with no negative effects on the kidneys

Combined treatment with myo-inositol and luteolin selectively suppresses growth of human lung cancer A549 cells possibly by suppressing activation of PDK1 and Akt / 南方医科大学学报

OBJECTIVE@#To study the effects of myo-inositol and luteolin on human lung cancer A549 cells and explore the possible mechanisms.@*METHODS@#A549 cells were treated with different concentrations of myo-inositol and luteolin, either alone or in combination, and the cell viability was examined using MTT assay. A549 cells and human bronchial epithelial Beas-2B cells were treated for 48 h with 10 mmol/L myo-inositol and 20 μmol/L luteolin, alone or in combination, and the cell proliferation was detected using MTT assay; the colony formation and migration of the cells were examined with colony formation assay and wound healing assay, respectively. The protein expression levels in A549 cells were detected using Western blotting.@*RESULTS@#Both myo-inositol and luteolin could dose-dependently inhibit the viability of A549 cells. Treatments with 10 mmol/L myo-inositol, 20 μmol/L luteolin, and both for 48 h caused significant reduction in the cell viability (92%, 83% and 70% of the control level, respectively) and colony number (79%, 73% and 43%, respectively), and significantly lowered the wound closure rate (24.61%, 13.08% and 8.65%, respectively, as compared with 29.99% in the control group). Similar treatments with myoinositol and luteolin alone or in combination produced no significant inhibitory effect on the growth, colony formation or migration of Beas-2B cells. The expressions of p-PDK1 and p-Akt in myo-inositol-treated A549 cells and the expression of pPDK1 in luteolin-treated cells were significantly decreased ( < 0.05), and the decrements were more obvious in the combined treatment group ( < 0.05).@*CONCLUSIONS@#Luteolin combined with myo-inositol can selectively inhibit the proliferation and migration of A549 cells, and these effects are probably mediated, at least in part, by suppressing the activation of PDK1 and Akt.

Calcium-sensing receptor-mediated L-tryptophan-induced secretion of cholecystokinin and glucose-dependent insulinotropic peptide in swine duodenum

This study aimed to elucidate the effect of tryptophan (Trp) on gut hormone secretion as well as the roles of the calcium-sensing receptor (CaSR) and its downstream signaling pathway in gut hormone secretion by assessing swine duodenal perfusion in vitro. Swine duodenum was perfused with Krebs-Henseleit buffer as a basal solution. Various concentrations (0, 10, and 20 mM) of Trp were applied to investigate its effect on gut hormone secretion. A CaSR antagonist was used to detect the involvement of CaSR and its signal molecules. The 20 mM Trp concentration promoted the secretion of cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP), elevated the mRNA level of CaSR, and upregulated the protein levels of CaSR, protein kinase C (PKC), and inositol trisphosphate receptor (IP3R). However, NPS 2143, an inhibitor of CaSR, attenuated the CCK and GIP release, reduced the mRNA level of CaSR, and decreased the protein levels of CaSR, PKC, and IP3R with 20 mM Trp perfusion. The results indicate that CCK and GIP secretion can be induced by Trp in swine duodenum in vitro, and the effect is mediated by CaSR and its downstream signal molecules PKC and IP3R.

Electroacupuncture ameliorate learning and memory by improving N -acetylaspartate and glutamate metabolism in APP/PS1 mice

OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. Methods N -Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.

Calcium Signaling in Salivary Secretion

Calcium has versatile roles in diverse physiological functions. Among these functions, intracellular Ca²⁺ plays a key role during the secretion of salivary glands. In this review, we introduce the diverse cellular components involved in the saliva secretion and related dynamic intracellular Ca²⁺ signals. Calcium acts as a critical second messenger for channel activation, protein translocation, and volume regulation, which are essential events for achieving the salivary secretion. In the secretory process, Ca²⁺ activates K⁺ and Cl⁻ channels to transport water and electrolyte constituting whole saliva. We also focus on the Ca²⁺ signals from intracellular stores with discussion about detailed molecular mechanism underlying the generation of characteristic Ca²⁺ patterns. In particular, inositol triphosphate signal is a main trigger for inducing Ca²⁺ signals required for the salivary gland functions. The biphasic response of inositol triphosphate receptor and Ca²⁺ pumps generate a self-limiting pattern of Ca²⁺ efflux, resulting in Ca²⁺ oscillations. The regenerative Ca²⁺ oscillations have been detected in salivary gland cells, but the exact mechanism and function of the signals need to be elucidated. In future, we expect that further investigations will be performed toward better understanding of the spatiotemporal role of Ca²⁺ signals in regulating salivary secretion.

Comparative effects of angiotensin II and angiotensin-(4-8) on blood pressure and ANP secretion in rats

Angiotensin II (Ang II) is metabolized from N-terminal by aminopeptidases and from C-terminal by Ang converting enzyme (ACE) to generate several truncated angiotensin peptides (Angs). The truncated Angs have different biological effects but it remains unknown whether Ang-(4-8) is an active peptide. The present study was to investigate the effects of Ang-(4-8) on hemodynamics and atrial natriuretic peptide (ANP) secretion using isolated beating rat atria. Atrial stretch caused increases in atrial contractility by 60% and in ANP secretion by 70%. Ang-(4-8) (0.01, 0.1, and 1 µM) suppressed high stretch-induced ANP secretion in a dose-dependent manner. Ang-(4-8) (0.1 µM)-induced suppression of ANP secretion was attenuated by the pretreatment with an antagonist of Ang type 1 receptor (AT₁R) but not by an antagonist of AT₂R or AT₄R. Ang-(4-8)-induced suppression of ANP secretion was attenuated by the pretreatment with inhibitor of phospholipase (PLC), inositol triphosphate (IP₃) receptor, or nonspecific protein kinase C (PKC). The potency of Ang-(4-8) to inhibit ANP secretion was similar to Ang II. However, Ang-(4-8) 10 µM caused an increased mean arterial pressure which was similar to that by 1 nM Ang II. Therefore, we suggest that Ang-(4-8) suppresses high stretch-induced ANP secretion through the AT₁R and PLC/IP₃/PKC pathway. Ang-(4-8) is a biologically active peptide which functions as an inhibition mechanism of ANP secretion and an increment of blood pressure.

Efficacy and Safety of "URSA Complex" in Subjects with Physical Fatigue: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fatigue is a common symptom both in diseases status and in healthy subjects. Various supplements and nutraceuticals for relieving of fatigue have been used. However, there are a few studies to evaluate the efficacy and the safety of the drug for fatigue alleviation, we conducted using URSA Complex to evaluate the efficacy on physical fatigue via score changes in the checklist individual strength (CIS).</p><p><b>METHODS</b>The study was designed as a multicenter, randomized, double-blind, placebo-controlled trial, with subjects randomized to one of the two arms, receiving either placebo or URSA Complex administered as identical capsules. The primary efficacy endpoints of this clinical trials are the ratio of improving CIS scores < 76 points in patients at the end (4 weeks). Secondary efficacy variables are as follows one is an improvement of fatigue and the other is an improvement of the liver enzyme.</p><p><b>RESULTS</b>The fatigue recovery rate in who had improved CIS scores of < 76 points were 70.0%, 50.9% in the therapy group and placebo group, respectively (P = 0.019). The fatigue recovery rate in CIS score was higher in URSA Complex therapy group than placebo group. The difference between therapy group and placebo group was statistically significant at 4 weeks later, but not 2 weeks.</p><p><b>CONCLUSIONS</b>Our results provided that the URSA Complex was effective in alleviating physical fatigue. The adverse event frequency in the therapy groups was similar to that in the placebo group.</p>

Descentralização das ações de vigilância epidemiológica em Pernambuco, Brasil / Decentralization of epidemiological surveillance in Pernambuco State, Brazil / Descentralización de la vigilancia epidemiológica en Pernambuco, Brasil

O objetivo do estudo foi analisar a relação entre o processo de descentralização da gestão do Sistema Único de Saúde (SUS) e o desenvolvimento das ações de vigilância epidemiológica em municípios de Pernambuco, Brasil. A estratégia de trabalho consistiu num estudo descritivo e exploratório qualitativo/quantitativo, com a realização de uma pesquisa de caráter documental e entrevistas semiestruturadas com informantes-chave, como também um estudo ecológico espacial e de série temporal, no qual foi traçada uma série histórica de dez anos (2001-2010), utilizando-se indicadores selecionados. O estudo evidenciou que o processo de descentralização em Pernambuco obteve adesão e evoluiu, porém com a existência de desigualdades e fragilidades no seu desenvolvimento, também apontadas pela oscilação nos resultados da série histórica dos indicadores selecionados. Assim, mesmo que o processo de descentralização das ações de vigilância epidemiológica ainda seja incipiente em alguns municípios, sabe-se que o papel de executor das ações promove o empoderamento do nível municipal, quando o mesmo passa a produzir as informações necessárias à tomada de decisão.

The study aimed to analyze the relationship between decentralization of the Brazilian Unified National Health System (SUS) and the development of epidemiological surveillance activities in municipalities (counties) in Pernambuco State, Brazil. This was an exploratory descriptive qualitative and quantitative study, including a document search, completion of semi-structured interviews by key informants, and an ecological spatial and time trend study of selected health indicators, covering a 10-year period (2001-2010). The study showed that municipalities adhered to the decentralization process, which was making progress in Pernambuco, but with inequalities and weaknesses in its development. There was also a fluctuation in the time series for the selected indicators. Thus, even though the decentralization of epidemiological surveillance is still incipient in some municipalities, their protagonist role in implementing the activities promotes empowerment at the local level by producing key information for decision-making.

El objetivo del estudio fue analizar la relación entre el proceso de descentralización del Sistema Único de Salud (SUS) y el desarrollo de acciones de vigilancia epidemiológica en los municipios de Pernambuco, Brasil. La estrategia de trabajo fue un estudio exploratorio descriptivo, cualitativo y cuantitativo, con la realización de una revisión documental, entrevistas semi-estructuradas con informantes clave, y un estudio ecológico espacial con una serie de tiempo de 10 años (2001-2010) de indicadores seleccionados. El estudio mostró que el proceso de descentralización en Pernambuco tiene adhesión y evolucionó, pero con la existencia de desigualdades y debilidades en su desarrollo, revelado también por la oscilación de la serie histórica de los indicadores. A pesar de que el proceso de descentralización de la vigilancia epidemiológica es aún incipiente en algunos municipios, se sabe que el papel de ejecutor de acciones promueve el empoderamiento del nivel municipal, cuando se comienza a producir información necesaria para la toma de decisiones.

Orthodontic treatment in patient with idiopathic root resorption: A case report

Multiple idiopathic external root resorption is a rare pathological condition usually detected as an incidental radiographic finding. External root resorption of permanent teeth is a multifactorial process related to several local and systemic factors. If an etiological factor cannot be identified for root resorption, the term "idiopathic" is applied. This report presents a case of multiple idiopathic apical root resorption. The condition was found in a young female patient seeking orthodontic treatment due to malocclusion. This kind of resorption starts apically and progresses coronally, causing a gradual shortening and rounding of the remaining root. Patients with this condition are not the ideal candidates for orthodontic treatment; however, the aim of this report is to describe an unusual case of idiopathic root resorption involving the entire dentition, and to present the orthodontic treatment of this patient. It describes the progress and completion of orthodontic therapy with satisfactory end results.

A reabsorção radicular externa idiopática é uma rara condição patológica, normalmente detectada como um achado fortuito radiológico. Trata-se de um processo multifatorial, relacionado a diversos fatores locais e sistêmicos. Se um fator etiológico não for identificado, a reabsorção radicular é classificada como idiopática. Apresentamos o caso de uma paciente do sexo feminino com reabsorção radicular idiopática, que procurou tratamento ortodôntico para corrigir uma má oclusão. Esse tipo de reabsorção começa apicalmente e evolui coronalmente, provocando o encurtamento gradual e o arredondamento da raiz remanescente. Os pacientes com essa condição não são os candidatos ideais para o tratamento ortodôntico, no entanto, o objetivo desse relato é descrever um caso incomum de reabsorção radicular idiopática que envolveu toda a dentição. Além disso, pretende-se apresentar o tratamento ortodôntico da paciente. Também são descritos o progresso e a conclusão do tratamento ortodôntico, assim como os satisfatórios resultados finais.