The Correlation Between CVP and SVV and Intraoperative Minimal Blood Loss in Living Donor Hepatectomy.

BACKGROUND: Blood loss during liver surgery is found to be correlated with central venous pressure (CVP). The aim of the current retrospective study is to find out the cutoff value of CVP and stroke volume variation (SVV), which may increase the risk of having intraoperative blood loss of more than 100 mL during living liver donor hepatectomies. METHOD AND PATIENTS: Twenty-seven adult living liver donors were divided into 2 groups according to whether they had intraoperative blood loss of less (G1) or more than 100 mL (G2). The mean values of the patients' CVP and SVV at the beginning of the transaction of the liver parenchyma was used as the cutoff point. Its correlation to intraoperative blood loss was evaluated using the χ2 test; P < .001 was regarded as significant. RESULTS: The cutoff points of CVP and SVV were 8 mm Hg and 13% respectively. The odds ratio of having blood loss exceeding 100 mL was 91.25 (P < .001) and 0.36 (P < .001) for CVP and SVV, respectively. CONCLUSION: CVP less than 5 mm Hg, as suggested by most authors, is not always clinical achievable. Our results show that a value of less than 8 mm Hg or SVV 13% is able to achieve a minimal blood loss of 100 mL during parenchyma transaction during a living donor hepatectomy. Measurements used to lower the CVP or increased SVV in our serial were intravenous fluids restriction and the use of a diuretic.

Neural stem cell transplantation at critical period improves learning and memory through restoring synaptic impairment in Alzheimer's disease mouse model.

Alzheimer's disease (AD) is characterized by neuronal loss in several regions of the brain. Recent studies have suggested that stem cell transplantation could serve as a potential therapeutic strategy to halt or ameliorate the inexorable disease progression. However, the optimal stage of the disease for stem cell transplantation to have a therapeutic effect has yet to be determined. Here, we demonstrated that transplantation of neural stem cells into 12-month-old Tg2576 brains markedly improved both cognitive impairments and neuropathological features by reducing ß-amyloid processing and upregulating clearance of ß-amyloid, secretion of anti-inflammatory cytokines, endogenous neurogenesis, as well as synapse formation. In contrast, the stem cell transplantation did not recover cognitive dysfunction and ß-amyloid neuropathology in Tg2576 mice aged 15 months when the memory loss is manifest. Overall, this study underscores that stem cell therapy at optimal time frame is crucial to obtain maximal therapeutic effects that can restore functional deficits or stop the progression of AD.

Intracellular domains of amyloid precursor-like protein 2 interact with CP2 transcription factor in the nucleus and induce glycogen synthase kinase-3beta expression.

Amyloid precursor protein (APP) is a member of a gene family that includes two APP-like proteins, APLP1 and 2. Recently, it has been reported that APLP1 and 2 undergo presenilin-dependent gamma-secretase cleavage, as does APP, resulting in the release of an approximately 6 kDa intracellular C-terminal domain (ICD), which can translocate into the nucleus. In this study, we demonstrate that the APLP2-ICDs interact with CP2/LSF/LBP1 (CP2) transcription factor in the nucleus and induce the expression of glycogen synthase kinase 3beta (GSK-3beta), which has broad-ranged substrates such as tau- and beta-catenin. The significance of this finding is substantiated by the in vivo evidence of the increase in the immunoreactivities for the nuclear C-terminal fragments of APLP2, and for GSK-3beta in the AD patients' brain. Taken together, these results suggest that APLP2-ICDs contribute to the AD pathogenesis, by inducing GSK-3beta expression through the interaction with CP2 transcription factor in the nucleus.

Subcellular localization of presenilins during mouse preimplantation development.

The genes defective in familial Alzheimer's disease encode the proteins presenilin 1 and 2 (PS1 and 2). Expression of presenilins (PSs) and their proteolytic processing are regulated during neuronal development. Even though these proteins are detected and regulated mainly in Golgi and endoplasmic reticulum, their subcellular distribution during the development is not known. The present study aimed to investigate the localization of PSs and their role during early developmental stage using mouse embryo model. At preimplantation stage, PSs were detected not only in cytoplasm, but also in the nucleus from oocyte to 2.5 dpc (day postcoitum), then disappeared in the nucleus at blastocyst stage (3.5 dpc). Antisense against PS1 and PS2 decreased the transition to blastocyst stage, whereas each antisense alone had no effect. Treatment with lactacystin (26S proteosome inhibitor), which arrest cell cycle at M phase, redistributed PSs into centrosome-kinetochore microtubule. PS2 overexpression in HEK 293 cell arrested cell cycle at S phase. These data suggest that PSs play key roles in cell division and differentiation during early development.

APP carboxyl-terminal fragment without or with abeta domain equally induces cytotoxicity in differentiated PC12 cells and cortical neurons.

Mutations in the beta-amyloid precursor protein (APP) gene cause familial Alzheimer's disease (AD). Although amyloid beta peptide (Abeta) is the principal constituent of senile plaques in AD, other cleavage products of APP are also implicated in playing a role in the pathogenesis of AD. C-terminal fragments of APP (APP-CTs), that contain complete Abeta sequence, are found in neuritic plaques, neurofibrillary tangles and the cytosol of lymphoblastoid cells obtained from AD patients. Our previous report demonstrated that APP-CT105 causes death of differentiated PC12 cells and cultured rat cortical neurons (Kim and Suh [1996] J. Neurochem. 67:1172-1182) and induces strong inward currents in Xenopus oocyte (Fraser et al., [1996] J. Neurochem. 66:2034-2040). In the present study, to investigate which domain of APP-CT105 is responsible for the neurotoxicity, we have made deletion mutants of APP-CT105 without Abeta and transmembrane domain (TM) or without NPTY domain, a putative endocytosis signaling sequence, using the PCR-amplified strategy and the recombinant GST-fusion protein strategy. The effect on cell survival of the deletion mutants of APP-CT105 (8 microM) was then determined by the LDH and MTT assay. We found that C-terminal fragment without NPTY significantly causes cell death in NGF-differentiated PC12 cells and cultured rat cortical neurons. This finding suggests that NPTY may not play an important role in APP-CT105 mediated neurotoxicity. We found, however, that C-terminal fragment without Abeta and TM significantly induces neuronal cell death. Our results suggest that in addition to Abeta, C-terminal fragment of APP without Abeta and TM domain itself may also participate in the neuronal degeneration in AD.

Inhibition of the NGF and IL-1beta-induced expression of Alzheimer's amyloid precursor protein by antisense oligonucleotides.

Alzheimer's disease (AD) is a neurodegenerative disorder of the brain characterized by the extracellular deposition of amyloid in senile plaques and along the walls of the cerebral vasculature. The principal constituent of amyloid deposit is amyloid beta peptide (Abeta) derived from its larger precursor protein, amyloid precursor protein (APP). The overexpression of APP is known to be a risk factor for Abeta deposit in AD and in Down syndrome (DS). The inhibition of APP expression has been thought to be beneficial to patients with AD and DS. In this study, we investigated the effects of antisense oligonucleotide (AO) on the overexpression of APP induced by IL-1beta and NGF. Using phosphorothioate-oligonucleotides against initiation codon significantly reduced the protein levels of APP induced by NGF and IL-1beta to basal level in PC12 cell culture systems. These results showed that these antisense oligonucleotides may have a potential to be a therapeutic agent for some patients with AD and DS.

The NTPase/helicase activities of Drosophila maleless, an essential factor in dosage compensation.

Drosophila maleless (mle) is required for X chromosome dosage compensation and is essential for male viability. Maleless protein (MLE) is highly homologous to human RNA helicase A and the bovine counterpart of RNA helicase A, nuclear helicase II. In this report, we demonstrate that MLE protein, overexpressed and purified from Sf9 cells infected with recombinant baculovirus, possesses RNA/DNA helicase, adenosine triphosphatase (ATPase) and single-stranded (ss) RNA/ssDNA binding activities, properties identical to RNA helicase A. Using site-directed mutagenesis, we created a mutant of MLE (mle-GET) that contains a glutamic acid in place of lysine in the conserved ATP binding site A. In vitro biochemical analysis showed that this mutation abolished both NTPase and helicase activities of MLE but affected the ability of MLE to bind to ssRNA, ssDNA and guanosine triphosphate (GTP) less severely. In vivo, mle-GET protein could still localize to the male X chromosome coincidentally with the male-specific lethal-1 protein, MSL-1, but failed to complement mle1 mutant males. These results indicate that the NTPase/helicase activities are essential functions of MLE for dosage compensation, perhaps utilized for chromatin remodeling of X-linked genes.

Effects of temperature on somatosensory evoked potentials during open heart surgery.

Somatosensory evoked potentials (SEPs) have been found to be useful for early detection of brain ischemia during hypothermic cardiopulmonary bypass in cardiac surgery. However, the relationship between temperature and latency period remains unclear. We prospectively analyzed SEPs obtained during hypothermic cardiopulmonary bypass in 20 patients who had valvular replacement. We concluded that i) a linear correlation was found between temperature and latency period during cooling and rewarming, ii) no hysteresis effect existed in cooling and rewarming, iii) there was a greater hypothermic effect on the synaptic transmission than on the conduction velocity, and iv) age had also more profound effect on relationship between temperature and latency of SEPs.

Comparison of P6 acupoint injection with 50% glucose in water and intravenous droperidol for prevention of vomiting after gynecological laparoscopy.

Postoperative vomiting causes patients distress and delays discharge after outpatient surgery. Although P6 electroacupuncture is recognized as having an antiemetic effect, its inconvenient instrumentation may limit its clinical applicability. The purpose of this study was to explore a simple and effective alternative method for control of postoperative vomiting in outpatient surgery. We prospectively compared the effect of P6 acupoint injection with 0.2 ml 50% glucose in water (G/W) and intravenous injection of 20 micrograms/kg droperidol for prevention of vomiting in 120 consecutive outpatients undergoing gynecological laparoscopy with general anesthesia. Patients were randomly allocated to receive P6 acupoint injection, i.v. droperidol, or nothing as control group. Both P6 acupoint injection and i.v. droperidol 20 micrograms/kg were found to have a significant antiemetic effect when compared with the control group. We conclude that P6 acupoint injection with 50% G/W is a simple and effective method for reducing the incidence of postoperative emesis in outpatient surgery.