Effect of Repeated Recruitment Manoeuvres on Patients with Severe Acute Respiratory Distress Syndrome.

OBJECTIVE: The study aimed to evaluate the influence of repeated recruitment manoeuvres (RRMs) on lung injury in patients with acute respiratory distress syndrome (ARDS). METHODS: Forty-one ventilated patients with severe ARDS were selected for this study. Recruitment manoeuvres (RMs) were conducted with continuous positive airway pressure (CPAP; 30 cm H2O for 40 seconds). Recruitment manoeuvres were repeated every two hours for all three groups. Changes in haemodynamics, pulmonary compliance, gas exchange and extravascular lung water index (EVLWI) were monitored before RM (pre-RM), 10 minutes after each RM, and four hours after RM3 (4 hours post-RRM). Pulmonary inflammatory factors (tumour necrosis factor-alpha [TNF-α] and interleukin [IL]-6 and -10) were also analysed. RESULTS: Compared with those in pre-RM, pulmonary compliance, oxygenation index (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen [PaO2/FiO2]) and EVLWI remarkably improved in RM1, RM2, RM3 and 4 hours post-RRM (p < 0.05). The PaO2/FiO2 ratio increased significantly in RM1 and RM3 (p < 0.05). Extravascular lung water index decreased significantly in RM1 compared with that in RM3 and 4 hours post-RRM (p < 0.05). There was no significant difference in cytokines. CONCLUSION: Repeated recruitment manoeuvres during lung-protected ventilation can improve pulmonary compliance and oxygenation and significantly decrease extravascular lung water in ARDS patients. Lung injury was not worsened by RRMs in patients with severe ARDS.

DNA sequencing identifies mutation of the von Hippel-Lindau gene in tubal pregnancy.

Genetic mutations in the von Hippel-Lindau (VHL) gene are common in certain diseases. The effects on the VHL gene in the tubal pregnancy tissues are unknown but with further study, it was found that the VHL gene may be related to prognosis or therapy selection. This study was conducted to analyse the VHL gene in tissues of human fallopian tube and tubal pregnancy. A total of 35 patients undergoing salpingectomy for tubal pregnancy were recruited into the experimental group. Samples of ampullary fallopian tube during mid-secretory phase were collected from 10 patients with benign uterine disease as the control group. Fluorescent dye dideoxy termination method was performed to detect three exons sequences of the VHL gene in tissues of both the human fallopian tube and tubal pregnancy. The DNA sequences of three exons of VHL gene coding region in tubal pregnancy were not found in mutations. The present study suggested that the VHL gene mutations were not related with tubal pregnancy.

Lactotripeptides intake and blood pressure management: a meta-analysis of randomised controlled clinical trials.

BACKGROUND AND AIMS: Lactotripeptides (LTPs, including IPP and VPP) have held promise in the framework of lifestyle modification for prevention and control of hypertension - a cardiovascular risk factor, as LTPs are reported to have an inhibitory effect on angiotensin-converting enzyme. While the number of clinical trials to test the efficacy of LTP continues to increase, the results have been inconsistent, especially in the last few years. The purpose of the present meta-analysis is to precisely estimate the pooled mean effect of LTPs on conventional blood pressure (BP) generally and on 24-h ambulatory BP (ABP) particularly, as well as the change of BP in relation to baseline BP, race, and study design, to better reflect the evolving field. DATA SYNTHESIS: In general analysis of 24 studies with 28 trials on 1919 human subjects, there are small reductions in both systolic BP (SBP) and diastolic BP (DBP) with the pooled mean effects of 1.66 (95% confidence interval (CI): -2.48 and -0.84) and 0.76 mmHg (-1.31 and -0.20) in response to LTP administration. In analysis of 24-h ABP response to LTP intervention, the reductions of SBP and DBP are 1.30 (-2.49 and -0.11) and 0.57 mmHg (-1.49 and 0.35). In subgroup analysis, the anti-hypertensive efficacy appears to be related to baseline BP, ethnic differences, treatment duration and double versus not double-blind design. CONCLUSIONS: The present findings indicate that the BP-lowering effect of LTP is statistically significant, though small in magnitude. More clinical investigations (especially randomized double-blind trials with ABP) are warranted to determine the anti-hypertensive efficacy of LTP conclusively.

The effects of gastric cancer interstitial fluid on tumors based on traditional Chinese medicine 'phlegm' theory and the investigation on the mechanism through microRNA-21 regulation.

This study aimed to investigate the effects of gastric cancer interstitial fluid (GCIF) on tumors and explore the possible mechanism of Xiaotan Sanjie decoction (XTSJ) on treatment of gastric cancer from the view of regulating microRNA-21 (miR-21) expression. The GCIF was extracted and identified by measuring the levels of interleukin-8 (IL-8), intercellular adhesion molecule 1 (ICAM-1) and miR-21. The effects of GCIF on the proliferation of SGC-7901 cells and tumor growing were assessed by cell counting kit-8 (CCK-8) assay and subcutaneously transplanted tumor-bearing nude mice model, respectively. Additionally, inhibition effect of XTSJ decoction on proliferation of SGC-7901 cells intervened by GCIF were assessed in vitro and anti-cancer effect of it was further assessed using orthotopic transplanted tumor-bearing nude mice model. The concentration of SGC-7901 gastric cancer cells were dependent on the concentration of the added GCIF. After 72 hours of continuous culture, the interstitial fluid had an obvious proliferative effect on the SGC-7901 tumor cells, which was the most significant in the high concentration group. XTSJ decoction could inhibit the growth-promoting effect (P < 0.01) of GCIF on gastric cancer cells. Intervention of the GCIF might promote the growth (P < 0.05) of the subcutaneously transplanted tumors in nude mice and decrease the net weight of the tumor-bearing nude mice (P < 0.05) after tumor removal. The GCIF was able to up-regulate the expression (P < 0.001) of miR-21 in the subcutaneously transplanted tumors. XTSJ decoction could downregulate the expression (P < 0.05) of miR-21 in SGC-7901 orthotopically transplanted tumors. XTSJ decoction can inhibit the multiplicative effect of GCIF on gastric cancer cells, growth of gastric tumor and promotion effect of GCIF on tumors, probably due to the down-regulating miR-21 expression in tumor tissues.

A Cross-Sectional Study of GLIM-Defined Malnutrition Based on New Validated Calf Circumference Cut-off Values and Different Screening Tools in Hospitalised Patients over 70 Years Old.

BACKGROUND AND AIMS: The Global Leadership Initiative on Malnutrition (GLIM) is new criteria for diagnosing malnutrition that need validation adjusted to race. Our aim is to determine the optimal reference values of calf circumference (CC), investigate the prevalence of GLIM-defined malnutrition based on different screening tools in inpatients over 70 years old in China and assess its relationship with clinical outcomes. METHODS: We designed two continuity studies by analyzing a prospective multicenter database. First, we estimated and validated the CC cut-off values by receiver operating characteristic analyses against in-hospital mortality. Then the patients who were at risk by NRS 2002, MNA-SF and MUST were assessed by the GLIM criteria using the new CC values. Some clinical parameters and outcome data were evaluated. RESULTS: The optimal cut-off values of CC were 29.6 cm for male patients and 27.5 cm for female patients. The prevalence of GLIM-defined malnutrition was 27.5% by using NRS2002, 32.6% by using MNA-SF and 25.4% by using MUST. Patients with GLIM-defined malnutrition showed significantly worse values in BMI, total protein, albumin, neutrophil/lymphocyte ratio, CC, rate of complication, in-hospital mortality, length of stay, and total hospital cost than normal patients. Multivariate logistic regression showed the odds ratio of in-hospital mortality was significantly associated with GLIM defined malnutrition by using MNA-SF [OR = 1.231, 95%CI (1.022, 1.484), P = 0.029]. CONCLUSIONS: The Chinese reference values of CC for inpatients over 70 years old were validated by in-hospital mortality, which could be implemented in GLIM criteria. And this population possessed a high prevalence of nutrition risk and malnutrition. GLIM criteria with MNA-SF seems to be the first choice to diagnose malnutrition.

A method for recording miniature inhibitory postsynaptic currents in the central nervous system suitable for quantal analysis.

Quantal analysis of transmitter release is useful in examining presynaptic mechanisms involved in synaptic transmission. However, in central neurons, the presence of multiple synapses makes it difficult to use the traditional quantal analysis, developed for the neuromuscular transmission. We developed a method to minimize these difficulties. Experiments were performed, using the whole-cell patch-clamp recording technique, on rat CA1 pyramidal neurons in a hippocampal slice preparation. When the stratum radiatum was stimulated, mixed current signals including, miniature inhibitory postsynaptic currents (mIPSCs), miniature excitatory postsynaptic currents (mEPSCs), evoked inhibitory postsynaptic currents (eIPSCs) and evoked excitatory postsynaptic currents (eEPSCs), could be observed in CA1 pyramidal cells while slices were superfused with the normal, Na(+)-containing, medium. The mIPSCs could be blocked by bicuculline (10 microm). mEPSCs, eEPSCs and eIPSCs could not be observed when the Na(+)-containing perfusion medium was replaced by a Na(+)-free medium but reappeared when the Na(+)-containing medium was re-introduced. When a polarizing electrode was placed near the recorded neuron, while slices were superfused with the Na(+)-free medium, and depolarizing rectangular current pulses of different magnitudes were applied, the number of mIPSCs increased with increasing amount of the current. Amplitudes of the mIPSCs showed a Gaussian distribution and the coefficient of variation was small. These observations indicate that a combination of the Na(+)-free superfusing medium and local depolarizations with a polarizing electrode is useful for recording mIPSCs from a localized area of the recorded neuron and for quantal analysis.

Increased expression of long non-coding RNA SBDSP1 correlates with poor survival in colorectal cancer.

OBJECTIVE: Long non-coding RNA SBDSP1 (SBDSP1) had been reported to be increased in colorectal cancer (CRC), but its effects on prognosis were still unclear. The aim of this study was to investigate the clinical significance and prognostic value of the SBDSP1 expression in CRC. PATIENTS AND METHODS: The expression levels of SBDSP1 in CRC tissues and adjacent normal tissues were detected using quantitative Real-time PCR (qRT-PCR). The association between SBDSP1 expression and clinicopathological factors as well as survival rates were analyzed. To determine the prognostic value of SBDSP1, univariate and multivariate analysis were performed using the Cox proportional hazard analysis. RESULTS: The relative expression levels of SBDSP1 were significantly higher in CRC tissues than in the matched normal colon tissues (p < 0.01). SBDSP1 expression was significantly associated with differentiation (p = 0.002), depth of invasion (p = 0.007) and TNM stage (p= 0.004). Additionally, patients with higher SBDSP1 expression have significantly shorter disease-free survival (p = 0.006) and overall survival (p = 0.001) compared to those with lower expression. Moreover, univariate and multivariate analysis identified high SBDSP1 expression as an unfavorable prognostic factor for both overall survival and disease-free survival. CONCLUSIONS: The present study provides the first evidence that SBDSP1 may be a useful indicator of prognosis in patients with CRC.

Human Umbilical Cord Mesenchymal Stem Cells: Subpopulations and Their Difference in Cell Biology and Effects on Retinal Degeneration in RCS Rats.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). OBJECTIVE: To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. METHODS: Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. RESULTS: Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression. Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1 displayed stronger colony forming potential as well as adipogenic and osteogenic differentiation capacities. When the two subsets were respectively transplanted into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1 expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1 showed stronger rescue effect on the retinal function as indicated by the higher b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased apoptotic photoreceptors. When both subsets were treated with interleukin-6, mimicking the inflammatory environment when the cells were transplanted into the eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic factors in comparison with hUC-MSC2. CONCLUSION: The data here, in addition to prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect, paracrine of trophic factors and potential RPE cell differentiation capacity. Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should be used for effective treatment of RD.

Theta bursts set up glutamatergic as well as GABA-ergic plasticity in neonatal rat hippocampal CA1 neurons.

gamma-Aminobutyric acid (GABA) is inhibitory in adult, but excitatory in neonatal, neurons. The switch from excitatory to inhibitory action is due to a negative shift in the equilibrium potential for the GABA(A) receptor-mediated postsynaptic current (E(GABA-PSC)). Here, we report that, in neonatal rat hippocampal CA1 neurons, presynaptic theta-burst activation induces not only a shift in E(GABA-PSC) towards that in adult neurons, but also a recruitment of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor-mediated postsynaptic currents.

Clinical research about airway pressure release ventilation for moderate to severe acute respiratory distress syndrome.

OBJECTIVE: To evaluate clinical effects of airway pressure release ventilation (APRV) in patients suffering from moderate to severe acute respiratory distress syndrome (ARDS).e of a patient presented with significant high aminotransferase levels due to the first human R. aeschlimannii infection ever detected in Italy. The hypothesis of rickettsiosis was made on the basis of a comprehensive medical history and was confirmed by serological tests. Molecular analyses made on a sample of hepatic tissue revealed the presence of a rickettsial species never found before in human liver. PATIENTS AND METHODS: From August 2012 to August 2014, fifty-two cases with moderate to severe ARDS were randomly divided into two groups. In the first group (APRV) the airway pressure release ventilation was used; the second group (SIMV) was ventilated using synchronized intermittent mandatory ventilation mode and positive end expiratory pressure (PEEP). Changes in oxygenation index, respiratory mechanics, extravascular lung water, functional residual capacity change and hemodynamics were recorded in both groups after mechanical ventilation. TNF-a and IL-10 levels in alveolar lavage were also measured. Acute physiology and chronic health evaluation (APACHE) II and Murray scores were evaluated. Pneumothorax and mediastinal emphysema during ventilation were also recorded. The probability of survival, the duration of ICU stay, days without organ failure and days without sedation were compared. RESULTS: Conditions in APRV were improved significantly. Oxygenation index was increased, airway peak pressure (Ppeak) was reduced, the lung dynamic compliance improved, extravascular lung water was relieved, functional residual capacity increased and Murray score was improved. In APRV group ventilation central venous pressure (CVP) and systemic circulation resistance index (SVRI) were reduced, but cardiac index (CI) increased, and at the same time lac and oxygen saturation of central venous blood (ScvO2) were improved. Free sedatives days were significantly reduced in APRV group while days without mechanical ventilation were increased and days in ICU were shortened significantly. TNF-α and IL-10 concentrations in the alveolar lavage, probability of survival and days without organ failure were similar in both groups. CONCLUSIONS: In patients suffering from moderate to severe ARDS, application of APRV improved lung function and hemodynamics. It also reduced the need for sedatives and the duration of mechanical ventilation as well as days in ICU.

Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration.

Bone marrow mesenchymal stem cells (BMSCs) have a therapeutic role in retinal degeneration (RD). However, heterogeneity of BMSCs may be associated with differential therapeutic effects in RD. In order to confirm this hypothesis, two subsets of rat BMSCs, termed rBMSC1 and rBMSC2, were obtained, characterized and functionally evaluated in the treatment of RD of Royal College of Surgeons (RCS) rats. Both subpopulations expressed mesenchymal stem cells (MSC) markers CD29 and CD90, but were negative for hemacyte antigen CD11b and CD45 expression. In comparison with rBMSC2, rBMSC1 showed higher rate of proliferation, stronger colony formation, and increased adipogenic potential, whereas rBMSC2 exhibited higher osteogenic potential. Microarray analysis showed differential gene expression patterns between rBMSC1 and rBMSC2, including functions related to proliferation, differentiation, immunoregulation, stem cell maintenance and division, survival and antiapoptosis. After subretinal transplantation in RCS rats, rBMSC1 showed stronger rescue effect than rBMSC2, including increased b-wave amplitude, restored retinal nuclear layer thickness, and decreased number of apoptotic photoreceptors, whereas the rescue function of rBMSC2 was essentially not better than the control. Histological analysis also demonstrated that rBMSC1 possessed a higher survival rate than rBMSC2 in subretinal space. In addition, treatment of basic fibroblast growth factor, an accompanying event in subretinal injection, triggered more robust increase in secretion of growth factors by rBMSC1 as compared to rBMSC2. Taken together, these results have suggested that the different therapeutic functions of BMSC subpopulations are attributed to their distinct survival capabilities and paracrine functions. The underlying mechanisms responsible for the different functions of BMSC subpopulation may lead to a new strategy for the treatment of RD.

Human Adipose-Derived Stem Cells Delay Retinal Degeneration in Royal College of Surgeons Rats Through Anti-Apoptotic and VEGF-Mediated Neuroprotective Effects.

UNLABELLED: Stem cell therapy is a promising therapeutic approach for retinal degeneration (RD). Our study investigated the effects of human adipose derived stem cell (hADSCs) on Royal College of Surgeons (RCS) rats. METHODS: Green fluorescent protein (GFP)-labeled hADSCs were transplanted subretinally into RCS rats at postnatal (PN) 21 days to explore potential therapeutic effects, while adeno-associated viral vector (AAV2)-vascular endothelial growth factor (VEGF) and siVEGF-hADSCs were used to aid the mechanistic dissections. Visual function was evaluated by Electroretinogram (ERG) recording. Potential transdifferentiations were examined by Immunofluorescence (IF) and gene expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Apoptotic retinal cells were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay and the cytokines secreted by hADSCs were measured by Enzyme-linked Immunosorbent Assay (ELISA). RESULTS: The visual function of RCS rats began to decrease one week after their eyes opened at PN week 3 and almost lost in PN 5 weeks, accompanied by the loss of retinal outer nuclear layer (ONL). Subretinal transplantation of hADSCs significantly improved the visual function 2 weeks after the transplantation and such therapeutic effect persisted up to 8 weeks after the treatment (PN 11 weeks), with 3-4 rows of photoreceptors remained in the ONL and reduced apoptosis. Consistent with these phenotypic changes, the gene expression of rod photoreceptor markers Rhodopsin (Rho), Crx and Opsin (Opn1) in RCS rats showed obvious decreasing trends over time after PN 3 weeks, but were elevated with hADSC treatment. hADSC transplantation also repressed the expressions of Bax, Bak and Caspase 3, but not the expression of anti-apoptotic genes, including Bcl-2 and Bcl-XL. Finally, substantial VEGF, hepatocyte growth factor (HGF) and pigment epithelium-derived factor (PEDF) secretions from hADSCs were detected, while endogenous Vegf expression level decreased over time in RCS rats. The treatment of AAV2-VEGF showed comparable therapeutic effects as hADSCs but siRNA knockdown of VEGF in hADSCs essentially abolished the therapeutic effects. CONCLUSIONS: Subretinal transplantation of hADSCs in RCS rats effectively delayed the retinal degeneration, enhanced the retinal cell survival and improved the visual function. Mechanistically this was mainly due to hADSC dependent anti-apoptotic and neuroprotective effects through its secretion of growth and neurotrophic factors including VEGF. Clinical application of hADSCs merits further investigation.

Benzodiazepine involvement in LTP of the GABA-ergic IPSC in rat hippocampal CA1 neurons.

Benzodiazepine binding sites are present on gamma-aminobutyric acid (GABA) receptors in hippocampal neurons. Diazepam is known to potentiate the amplitude and prolong the decay of GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs). In this study, benzodiazepine involvement in long-term potentiation (LTP) of the IPSC was examined. Whole-cell recordings of IPSCs were made from rat hippocampal CA1 neurons in a slice preparation. LTP was induced by a tetanic stimulation in the stratum radiatum (2 trains of 100 Hz for 1 s, 20 s inter-train interval) while pharmacologically blocking ionotropic glutamate receptors. During LTP, the amplitude of the IPSCs was potentiated in the majority of neurons with the IPSC decay and shape unaffected. Diazepam (5 microM) potentiated the IPSC amplitude and prolonged the decay when applied before, but not during, LTP. In neurons in which LTP could not be induced by a tetanic stimulation, diazepam did not increase the amplitude of the pre-tetanic IPSC. Flumazenil, at a concentration (10 microM) that blocked the enhancement of the IPSC by applied diazepam, had no effect on the IPSC amplitude when applied before LTP induction but significantly decreased the IPSC when applied during LTP maintenance. The antagonist, when applied during the tetanic stimulation, did not block LTP, suggesting that benzodiazepine receptors do not participate in LTP induction. These results indicate that the maintenance of LTP of the IPSC involves (a) the release of endogenous benzodiazepine agonist(s) and/or (b) the participation of benzodiazepine binding sites on subsynaptic GABA(A) receptors.

Milk/dairy products consumption, galactose metabolism and ovarian cancer: meta-analysis of epidemiological studies.

Ovarian cancer is the fifth most common cause of cancer death among women and the leading cause of gynaecological cancer death in the United States. Milk/dairy products consumption was considered to be a risk factor for ovarian cancer mainly because milk carbohydrate-lactose and galactose metabolism is toxic to oocytes. However, recent evidence does not support this hypothesis completely. We collected epidemiological studies related to the association between milk/dairy products consumption or galactose metabolism (lactose, galactose, galactose-1-phosphate uridyltransferase, lactose/transferase) and ovarian cancer published between January 1966 and August 2003 and found 27 items from 22 independent studies. Twenty studies were case-control studies and the other two were cohort studies. A meta-analysis method was conducted to estimate relative risk combining all relative data. In general, we did not find any association between milk/dairy products or galactose metabolism and ovarian cancer risk in this meta-analysis. The consumption of whole milk and butter, which contain relatively high amounts of fat, was positively (relative risk > 1.2), but not significantly, associated with an increased risk.

Spatial confinement of laser light in active random media

We have observed spatial confinement of laser light in micrometer-sized random media. The optical confinement is attributed to the disorder-induced scattering and interference. Our experimental data suggest that coherent amplification of the scattered light enhances the interference effect and helps the spatial confinement. Using the finite-difference time-domain method, we simulate lasing with coherent feedback in the active random medium.

Efficacy of continuous renal replacement therapy in the treatment of severe acute pancreatitis associated acute respiratory distress syndrome.

OBJECTIVE: To investigate the efficacy of the treatment of severe acute pancreatitis (SAP) complicated by acute respiratory distress syndrome (ARDS) using continuous renal replacement therapy (CRRT) by evaluating the effect of CRRT on respiratory and circulatory function as well as serum cytokines level. PATIENTS AND METHODS: Fifty four randomly selected patients with confirmed SAP complicated by ARDS after being admitted to intensive care unit (ICU) within 72 hr of onset were included in the study. Patients received mechanical respiratory support and CRRT. Arterial blood gas analysis was conducted and serum cytokine levels, including tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4) and interleukin 6 (IL-6), as well as C reactive protein (CRP) were evaluated respectively both before and 6h, 12h, and 24h after CRRT therapy. Peak inspiratory pressure and pulmonary compliance were also recorded. RESULTS: Arterial oxygen tension (PaO2), oxygenation index (OI) as well as dynamic pulmonary compliance were all elevated significantly, whereas peak inspiratory pressure significantly decreased at 6h, 12h and 24h after CRRT respectively; serum cytokine level and CRP significantly decreased (p < 0.05). CONCLUSIONS: CRRT can effectively reduce the level of inflammatory mediators, and improve respiratory and circulatory function.

Activity-mediated plasticity of GABA equilibrium potential in rat hippocampal CA1 neurons.

The equilibrium potential (E(GABA)(-PSC)) for gamma-aminobutyric acid (GABA) A receptor mediated inhibitory postsynaptic currents (PSCs) in hippocampal CA1 pyramidal neurons shifts when theta-burst stimulation (four pulses at 100 Hz in each burst in a train consisting of five bursts with an inter-burst interval of 200 ms, the train repeated thrice at 30-s intervals) is applied to the input. E(GABA)(-PSC) is regulated by K(+)/Cl(-) co-transporter (KCC2). GABA(B) receptors are implicated in modulating KCC2 levels. In the current study, the involvement of KCC2, as well as GABA(B) receptors, in theta-burst-mediated shifts in E(GABA)(-PSC) was examined. Whole-cell patch recordings were made from hippocampal CA1 pyramidal neurons (from 9 to 12 days old rats), in a slice preparation. Glutamatergic excitatory postsynaptic currents were blocked with dl-2-amino-5-phosphonovaleric acid (50 microM) and 6,7-dinitroquinoxaline-2,3-dione (20 microM). The PSC and the E(GABA)(-PSC) were stable when stimulated at 0.05 Hz. However, both changed following a 30-min stimulation at 0.5 or 1 Hz. Furosemide (500 microM) and KCC2 anti-sense in the recording pipette but not bumetanide (20 or 100 microM) or KCC2 sense, blocked the changes, suggesting KCC2 involvement. Theta-burst stimulation induced a negative shift in E(GABA)(-PSC), which was prevented by KCC2 anti-sense; however, KCC2 sense had no effect. CGP55845 (2 microM), a GABA(B) antagonist, applied in the superfusing medium, or GDP-beta-S in the recording pipette, blocked the shift in E(GABA)(-PSC). These results indicate that activity-mediated plasticity in E(GABA)(-PSC) occurs in hippocampal CA1 pyramidal neurons and theta-burst-induced negative shift in E(GABA)(-PSC) requires KCC2, GABA(B) receptors and G-protein activation.

The involvement of GABA-C receptors in paired-pulse depression of inhibitory postsynaptic currents in rat hippocampal CA1 pyramidal neurons.

In rat hippocampal CA1 pyramidal neurons, gamma-aminobutyric acid (GABA) A receptor-mediated inhibitory postsynaptic currents (IPSCs) undergo a paired-pulse depression (PPD) by the second of two pulses, with inter-pulse intervals of 100-2000 ms, applied to the stratum radiatum. While GABA-C receptors are described in the CA1 area, their functional significance is unknown. In this study, the involvement of GABA-C receptors in PPD was examined using an in vitro hippocampal slice preparation. IPSCs evoked by stimulations in stratum radiatum were recorded with patch pipettes from CA1 pyramidal cells. PPD, when induced in the above fashion, was blocked by the GABA-C receptor antagonist (1,2,5,6-Tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA, 10 muM, applied in the superfusing medium). GABA-A and GABA-B receptor-mediated IPSCs, as well as the baclofen-induced suppression of the GABA-A receptor mediated IPSC, were not antagonized by TPMPA (10-20 muM). These results indicate that PPD of the IPSC is mediated by the activation of GABA-C receptors.