Human entorhinal gamma and theta oscillations selective for remote autobiographical memory

Current source densities in different layers of the human entorhinal cortex (ER) were recorded using a linear array of 24 microelectrodes during three memory conditions: a remote autobiographical condition eliciting recollections of events that occurred 10 or more years ago in the participant's past, a semantic icon condition invoking the mental image of a well‐known object, and a semantic knowledge condition asking about general information. Our data demonstrate theta, gamma, and delta oscillations in left ER particularly for remote autobiographical memory. Gamma is predominant in hippocampally projecting layers during presentation of the memory cue, whereas theta is prolonged and dominant in cortically projecting layers during memory retrieval. Gamma interactions between ER and hippocampal formation (HF) may elicit an HF contribution to recall under influences relayed from the association cortex (AC). This contribution may then be relayed back to AC during retrieval of the memory orchestrated by theta interactions with ER. Accordingly, theta oscillations were recorded simultaneously in frontal and temporal cortices. © 2009 Wiley‐Liss, Inc.     

Rapid sequence induction for appendectomies: a retrospective case-review analysis

Purpose

Rapid sequence induction (RSI) with cricoid pressure is suggested to decrease the risk of aspiration of gastric contents. However, the effectiveness of RSI has been questioned, and the technique may lead to airway and hemodynamic complications. The purpose of this study was to determine the frequency of RSI use in patients with acute appendicitis, the types of drugs administered, and the occurrence of any complications.

Methods

After approval by the Ethics Committee, the charts of patients undergoing appendectomy in a one-year period were examined retrospectively. Information was retrieved on Mallampati airway evaluation, airway device used, preoxygenation, RSI, and drugs at induction. Reported complications were noted, including airway difficulties, hypotension (systolic blood pressure < 80 mmHg) and hypertension (>160 mmHg) in the 20-min period after induction.

Results

General anesthesia with tracheal intubation was used in 248 of 250 cases reviewed. The Mallampati airway evaluation, preoxygenation, and RSI were recorded as performed in 95, 94, and 81% of cases, respectively. Opioids, propofol, and neuromuscular blocking agents were given in 98, 98, and 99% of patients, respectively. Succinylcholine use was common (80%), with 96% of these patients receiving rocuronium precurarization. Difficult intubation with successful alternate technique was encountered in three patients (1.2%). Hypotension and hypertension occurred in 27% and 8% of patients, respectively. There were no documented cases of aspiration. Oxygen desaturation was mentioned in one case at induction and in three cases at emergence.

Conclusion

An RSI with opioid, induction agent, and succinylcholine is the technique of choice for appendectomies at our institution. The frequency of airway complications is too low to recommend a change in practice.     

Sleep Apnea Is Associated with Cardiovascular Risk Factors among Kidney Transplant Patients

Background and objectives: We assessed the prevalence of obstructive sleep apnea (OSA) and its clinical correlates in a large sample of patients who received a kidney transplant (Tx). We also compared the prevalence of the disorder between dialysis patients who were on the waiting list for a Tx (WL) and Tx patients.Design, setting, participants, & measurements: This was a cross-sectional study of 100 Tx and 50 WL patients who underwent one-night polysomnography (SLeep disorders Evaluation in Patients after kidney Transplantation [SLEPT] Study). Sociodemographic information and data about medication, comorbidity, and laboratory parameters were collected.Results: The prevalence of mild (apnea-hypopnea index [AHI] ≥5/h and <15/h), moderate (AHI ≥15/h and <30/h), and severe OSA (AHI ≥30/h) was 18, 11, and 14% in the Tx group and 28, 16, and 10% in the WL group, respectively. The AHI was significantly correlated with age (ρ = 0.34), body mass index (ρ = 0.45), neck circumference (ρ = 0.4), abdominal circumference (ρ = 0.51), and hemoglobin (ρ = 0.24) in the Tx group. The proportion of Tx patients who were treated with three or more antihypertensive drugs was significantly higher in the OSA group (56 versus 31%; P = 0.022). Despite taking significantly more antihypertensive drugs, the average systolic BP was still higher in patients with versus without OSA (147 ± 21 versus 139 ± 18 mmHg; P = 0.059).Conclusions: The prevalence of OSA is similar in Tx and WL patients and it may contribute to presence of hypertension in patients who receive a Tx.Obstructive sleep apnea (OSA) is the most clinically important form of sleep-related breathing disorders. The severity of OSA is generally characterized by the apnea-hypopnea index (AHI), which is the number of apneic and hypopneic events per hour of sleep.The prevalence of moderate and severe OSA syndrome (OSAS; AHI ≥15 and the presence of daytime symptoms of OSA) is 2 to 4% in the general population (1) and is associated with increased cardiovascular morbidity and mortality (2,3). OSAS is reportedly associated with higher risk for stroke, hypertension, diabetes, congestive hearth failure, arrhythmias, and the metabolic syndrome and also with fatal and nonfatal cardiovascular events (4–7)Previous studies have shown high prevalence of OSA (16 to 54%) in patients with chronic kidney disease (CKD) (8,9). Unruh et al. (10) showed that OSA is more common in hemodialysis patients than in general population.Although OSA may contribute to the increased cardiovascular risk seen in Tx patients, consistent information about OSA in patients who have received a kidney transplant (Tx) is scarce. Previously, we found that the prevalence of high risk for OSAS is approximately 30% in both WL and Tx patients (11). A case series indicated that AHI did not change after transplantation in 73% of the patients (12). Conversely, Mallamaci et al. (13) recently reported that 22% of renal Tx recipients had a respiratory disturbance index >5, which was similar to results seen in the general population.We designed this cross-sectional study to determine the prevalence and clinical correlates of OSA in a large, randomly selected sample of Tx patients using polysomnography. On the basis of our previous findings, we hypothesized that the prevalence of OSA would be similarly high in Tx and WL patients. Finally, we expected to find an increased cardio- and cerebrovascular risk in patients with versus without OSA in the Tx population.     

Lipoamino acids as major components of absorption promoters in drug delivery

Many biologically active compounds are unsuitable for development as drugs due to their poor bioavailability. For hydrophilic compounds, modifications to increase lipophilicity can increase passive diffusion or increase uptake into the lymphatic system. Alternatively, improved bioavailability of hydrophilic drug candidates may be achieved by formulation with absorption promoters such as surfactants, penetration enhancers, or ion pairing agents. This approach to enhancing bioavailability also has the potential to widen the range of compound categories that can be used as chemical probes to study biological systems in cells and in vivo where membrane permeability would otherwise be a significant limitation. Lipidic amino acids, which combine the structural properties of lipids with those of α-amino acids, represent a relatively unexplored class of agents that can improve drug adsorption. This review discusses the potential of absorption promoters possessing lipoamino acids for improving drug bioavailability.     

Advances in Peptide-based Human Papillomavirus Therapeutic Vaccines

Cervical cancer is the second leading cause of cancer in women worldwide. Human papillomavirus (HPV) is responsible for all cases of cervical cancer. Commercial prophylactic HPV vaccines are now available, but unfortunately these vaccines have no therapeutic effect against established HPV infections. In order to accelerate the control of cervical cancer and treat established HPV infections, it is necessary to develop therapeutic vaccines to eradicate HPV by generating cell-mediated immunity against HPV infected cells. Two HPV-encoded early proteins, the E6 and E7 oncoproteins, are the preferred targets because they are consistently expressed in virtually all cervical cancer cells and are necessary for the induction and maintenance of HPV-associated disease. A variety of vaccine strategies have been employed targeting immune responses to these proteins. Peptide-based vaccines are a promising strategy for the development of therapeutic HPV vaccines because of their safety, stability, and ease of production. This review summarizes the prospects of peptidebased vaccines for the treatment of established HPV infections. We address the challenges that scientists currently face for developing peptide-based vaccines and explore feasible strategies for improving the potency of the induced immune response with the aim of treating established HPV infections.     

Development and characterization of anionic liposaccharides for enhanced oral drug delivery

The aim of this study was to synthesize charged amphoteric molecules, which after complexation with poorly bioavailable drugs would have the potential to improve their oral uptake. Novel anionic liposaccharide derivatives containing d-glucose and lipoamino acids were synthesized by solution phase peptide synthesis. High sensitivity isothermal titration microcalorimetry was used to determine the critical aggregation concentration and the thermodynamic profiles. Hemolytic and cytotoxic activities of the liposaccharides were studied and they revealed that the liposaccharides were non-toxic at the concentration used for oral administration. Mixing a model drug, tobramycin, with the liposaccharide containing two lipids formed aggregates around 200 nm, which increased tobramycin partitioning between n-octanol/water. The results suggested that the studied liposaccharide with two lipids was safe to apply biologically and may have an absorption enhancing activity on hydrophilic, orally poorly available drugs.     

Preclinical (1)H-MRS neurochemical profiling in neurological and psychiatric disorders

The ongoing development of animal models of neurological and psychiatric disorders in combination with the development of advanced nuclear magnetic resonance (NMR) techniques and instrumentation has led to increased use of in vivo proton NMR spectroscopy ((1)H-MRS) for neurochemical analyses. (1)H-MRS is one of only a few analytical methods that can assay in vivo and longitudinal neurochemical changes associated with neurological and psychiatric diseases, with the added advantage of being a technique that can be utilized in both preclinical and clinical studies. In this review, recent progress in the use of (1)H-MRS to investigate animal models of neurological and psychiatric disorders is summarized with examples from the literature and our own work.