[Totally endoscopic sublay repair (TES)--a novel approach to repair midline ventral hernia].

Objective: Investigating a novel approach to treat a midline ventral hernia--totally endoscopic sublay repair (TES). The procedure will be described in detail and the safety and efficacy evaluated. Methods: During July and December 2017, eleven consecutive cases of primary and secondary epigastric midline ventral hernias were repaired using the TES procedure. A large mesh should be placed in the retrorectus position using this minimally invasive procedure. The indications for this procedure include umbilical, epigastric and incisional hernia equal in length to the rectus diastasis. Results: All operations were successful without open conversion. The mean operation time was 120 mins(80-205 min), postoperative pain was mild and the mean VAS was 2.5 on first postoperative day. The average postoperative stay in hospital was 3.3 days (2-5 days). 2 cases experienced postoperative seroma but without adverse effect on the final outcome and no recurrences during the follow-up period of 1 to 6 months. Conclusions: TES procedure is safe, practical and minimally invasive requiring no specific device and highly reproducible. Besides there is no need for expensive anti-adhesion mesh and fixation tacker which make it more cost effective. TES is a good technique for the surgical treatment of midline ventral hernia.

Sleep disorders of acute thalamic stroke and its influence on plasma IL-17.

The aim of this study was to investigate the relationship between sleep disorders in acute thalamus stroke patients and plasma IL-17 levels and the mechanism through which inflammatory reactions develop in stroke. The study included two groups of patients: an experimental group consisting of 30 patients with thalamus stroke who received treatment at the Affiliated Hong Qi Hospital of Mu Dan Jiang Medical University during October 2015 to October 2016 and a control group consisting of 15 healthy volunteers. All the subjects included in the study were biochemically monitored for blood glucose, blood fats and IL-17 plasma levels. The sleep quality of all the subjects included in the study was evaluated [Epwort, Pittsburgh Sleep Quality Index (PSQI)] with 8-hour Polysonmography (PSG) monitoring. The experimental group was divided into 3 subgroups according to the part of the brain affected by stroke: anterior thalamus nucleus group, lateral thalamus nucleus group and medial thalamus nucleus group. The differences were analyzed between the experimental group and the control group in sleep quality scores, sleep structural changes, and plasma IL-17 levels. The differences in sleep structural scores were also analyzed according to different parts of the brain affected by stroke. The experimental group had a higher PSQI score compared with the control group, but this difference had no statistical significance (p>0.05). Compared with the control group, the N1 phase of the experimental group was longer while the N2 and N3 phases were shorter (p<0.05). There were no differences in sleep structure between the three regions of the brain affected by stroke (anterior thalamus nucleus group, lateral thalamus nucleus group and medial thalamus nucleus group) (p > 0.05). The plasma levels of IL-17 in the experimental group was higher compared to the control group (p<0.05). In the experimental group, the patients with hypersomnia had higher IL-17 levels than patients without hypersomnia (p<0.01). We can conclude that PSG can be used as an electrophysiology index for early detection of sleep disorders in thalamus stroke patients. Sleep disorders in patients with thalamus stroke persist a long time after the incident, therefore monitoring their sleep structure may become an important index to predict the prognosis of the disease. The increased level of IL-17 level in the experimental group shows its implication in appearance of sleep disorders of acute thalamus stroke through inflammatory mechanism.

Linking of Glycine Receptor Transmembrane Segments Three and Four Allows Assignment of Intrasubunit-Facing Residues.

Glycine receptors (GlyRs) are pentameric ligand-gated ion channels that mediate inhibitory neurotransmission in the brain and spinal cord and are targets of alcohols and anesthetics. The transmembrane (TM) domain of GlyR subunits is composed of four α-helical segments (TM1-4), but there are conflicting data about the orientation of TM3 and TM4 and, therefore, also the proximity of residues (e.g., A288) that are important for alcohol and anesthetic effects. In the present study, we investigated the proximity of A288 in TM3 to residues in TM4 from M404 to K411. We generated eight double mutant GlyRs (A288C/M404C, A288C/F405C, A288C/Y406C, A288C/W407C, A288C/I408C, A288C/I409C, A288C/Y410C, and A288C/K411C), as well as the corresponding single mutants, and expressed them in Xenopus laevis oocytes. To measure glycine responses, we used two-electrode voltage clamp electrophysiology. We built homology models of the GlyR using structures of the nicotinic acetylcholine receptor (nAChR) and a prokaryotic ion channel (Gloeobacter violaceus, GLIC) as templates, and asked which model best fit our experimental data. Application of the cross-linking reagent HgCl(2) in the closed state produced a leftward shift in the glycine concentration-response curves of the A288C/W407C and A288C/Y410C mutants, suggesting they are able to form cross-links. In addition, when HgCl(2) was coapplied with glycine, responses were changed in the A288C/Y406C, A288C/I409C, and A288C/Y410C double mutants, suggesting that agonist-induced rotation of TM4 allows A288C/Y406C and A288C/I409C to cross-link. These results are consistent with a model of GlyR, based on nAChR, in which A288, Y406, W407, I409, and Y410 face into a four-helical bundle.

Improvement of monocyte function and immune homeostasis by high volume continuous venovenous hemofiltration in patients with severe acute pancreatitis.

BACKGROUND: Continuous renal replacement therapy (CRRT) showed promising results in the management of critically ill patients with systemic inflammatory response syndrome (SIRS)/sepsis. However, the underlying mechanism is still not very clear. A change of immune homeostasis in critically ill patients during CRRT was observed only to a smaller degree. OBJECTIVE: The purpose of this study was to test the hypothesis that high-volume continuous venovenous hemofiltration (HV-CVVH) treatment could improve monocyte function and restore immune homeostasis in patients with severe acute pancreatitis (SAP). METHODS: This was a prospective clinical trial in the surgical intensive care unit of a teaching hospital. Subjects were 16 patients with severe acute pancreatitis: sepsis group (n=7): positive culture result and in the late phase of disease (from onset of SAP to receiving CVVH therapy: more than 3 days); and nonseptic group (n=9): negative culture result and early phase of disease (less than 3 days). Patients received 72 hours of HV-CVVH. We measured the change in mean arterial pressure, APACHE II score, monocyte functions (including antigen-presenting and cytokine production ability), and plasma cytokines. RESULTS: Mean arterial pressure were stable accompanied with APACHE II score improvements. HLA-DR expression on monocytes (antigen-presenting ability) were markedly decreased (p<0.0001) in all patients. Lipopolysaccharide (LPS)-induced TNF-alpha, interleukin-6 (IL-6), and IL-10 production from patients' monocytes markedly decreased in septic patients, but significantly increased in nonseptic patients. During HV-CVVH treatment, HLA-DR expression was markedly increased in nonseptic patients in 24 hours (p<0.05), and in septic patients in 72 hours (p<0.05). LPS-induced cytokine production was decreased in nonseptic patients, but not significantly changed in septic patients. The change of plasma cytokines showed the same trend. CONCLUSIONS: In patients with SAP, HV-CVVH was associated with improved hemodynamics. HV-CVVH restores monocytes functions, especially in patients in the early phase of the disease and without sepsis. These findings suggest a potential role for HV-CVVH in the treatment of SAP.

Continuous veno-venous hemofiltration in the treatment of acute severe hyponatremia: a report of 11 cases.

OBJECTIVES: To evaluate the treatment effect of continuous veno-venous hemofiltration (CVVH) in patients with acute severe hyponatremia. METHODS: Eleven patients with severe acute hyponatremia, including 6 males and 5 females, aged 25-61 years (mean age 48.36), were treated with CVVH. Hyponatremia occurred 38-48 hours prior to the initiation of CVVH. RESULTS: All patients tolerated CVVH well, with an average treatment duration of 57.19 (45.6-86) hours. During CVVH, the serum sodium concentration increased significantly from 100.9+/-3.99 mmol/L at initiation of CVVH to 140.3+/-1.6 mmol/L after 48 hours of treatment (P<0.01). The serum osmolarity increased concurrently, from 216.7+/-7.4 mOsm/kgH2O to 295.0+/-4.2 mOsm/kgH2O (P<0.01). The Glasgow scores and APACHE II scores in these patients improved significantly during treatment. CONCLUSIONS: CVVH is a safe and effective option for the treatment of patients with severe acute hyponatremia due to its slow and continuous nature.

Does acetaldehyde mediate ethanol action in the central nervous system?

BACKGROUND: Some of the effects of ethanol in the central nervous system are due to changes in function of ligand-gated ion channels. Production of detectable amounts of acetaldehyde, a primary metabolite of ethanol, has been demonstrated in brain homogenates. The aim of this study was to determine whether central actions that are often attributed to ethanol may actually be mediated by acetaldehyde. METHODS: The effects of acetaldehyde (1-1000 microM) were tested by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand-gated ion channel receptors [alpha1 glycine; alpha1beta2gamma2Sgamma-aminobutyric acid (GABA)A; rho1 GABAc; 5-hydroxytryptamine-3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA; GluR6/KA2 kainate; and alpha4beta2, alpha4beta4, and alpha2beta4 nicotinic-acetylcholine] and the G-protein-coupled inward rectifying potassium channel GIRK2. We also investigated the effect of acetaldehyde on the dopamine transporter (DAT), performing dopamine uptake assays in oocytes expressing DAT. RESULTS: Acetaldehyde (1 and 10 microM) significantly enhanced alpha1 glycine receptor-mediated currents. Acetaldehyde did not affect the function of any of the other receptors tested or the potassium currents measured in GIRK2 channels. Moreover, acetaldehyde did not alter the DAT-mediated dopamine uptake. CONCLUSIONS: Our results suggest a potential minor role for acetaldehyde in the glycine receptor-mediated effects of ethanol. Otherwise, acetaldehyde does not modulate function of the neuronal receptors tested in this study, in GIRK channels or DAT, when expressed recombinantly in Xenopus laevis oocytes.

The anesthetic potency of propanol and butanol versus propanethiol and butanethiol in alpha1 wild type and alpha1(S267Q) glycine receptors.

UNLABELLED: Although similar in shape and size, and although differing only by substitution of a sulfur atom for an oxygen atom, propanethiol and butanethiol differ markedly from propanol and butanol in their in vivo potency and physical properties. Recent theories of narcosis suggest that anesthetics may act by enhancing the effect of inhibitory agonists, such as glycine, on their receptors. We tested whether propanol, butanol, propanethiol, and butanethiol enhance the effect of glycine on alpha1 glycine receptors expressed in Xenopus laevis oocytes in a manner that reflects the in vivo differences found for potencies. As anticipated, we found an immediate parallel between in vivo (rat minimum alveolar concentration of anesthetic required to eliminate movement in response to a noxious stimulus in 50% of subjects) and in vitro (recombinant receptor) effects. All four compounds enhanced the effect of glycine on wild type receptors, and the extent of enhancement for a given minimum alveolar concentration-multiple was approximately the same for all compounds. We also found that propanethiol, butanethiol, propanol, and butanol did not affect, or minimally affected, the action of glycine in anesthetic resistant mutants in which the amino acid serine at position 267 was replaced by glutamine [alpha1(S267Q)]. IMPLICATIONS: The in vivo potencies of propanethiol, butanethiol, propanol, and butanol correlate with their capacities to enhance the effect of glycine on alpha1 glycine receptors expressed in Xenopus laevis oocytes. These results support the notion that a protein mediates anesthetic action.

The anesthetic potencies of alkanethiols for rats: relevance to theories of narcosis.

UNLABELLED: Meyer and Overton suggested that anesthetic potency correlates inversely with lipophilicity. Thus, MAC times the olive oil/gas partition coefficient equals an approximately constant value of 1.82 +/- 0.56 atm (mean +/- SD). MAC is the minimum alveolar concentration of anesthetic required to eliminate movement in response to a noxious stimulus in 50% of subjects. Although MAC times the olive oil/gas partition coefficient also equals an approximately constant value for normal alkanols from methanol through octanol, the value (0.156 +/- 0.072 atm) is 1/10th that found for conventional anesthetics. We hypothesized that substitution of sulfur for the oxygen in n-alkanols would decrease their saline/gas partition coefficients (i.e., decrease polarity) while sustaining lipid/gas partition coefficients. Further, we hypothesized that these changes would produce products of MAC times olive oil partition coefficients that approximate those of conventional anesthetics. To test these predictions, we measured MAC in rats, and saline and olive oil solubilities for the series H(CH(2))(n)SH, comparing the results with the series H(CH(2))(n)OH for compounds having three to six carbon atoms. As hypothesized, the alkanethiols had similar oil/gas partition coefficients, 1000-fold smaller saline gas partition coefficients, and MAC values 30 times greater than for comparable alkanols. Such findings are consistent with the notion that the greater potency of many alkanols (greater than would be predicted from conventional inhaled anesthetics and the Meyer-Overton hypothesis) results from their greater polarity. IMPLICATIONS: The in vivo anesthetic potency of alkanols and alkanethiols correlates with their lipophilicity and hydrophilicity.

Glycine and gamma-aminobutyric acid(A) receptor function is enhanced by inhaled drugs of abuse.

Inhalable solvents possess significant abuse liability and produce many of the neurobehavioral effects typically associated with central nervous system-depressant agents, including motor incoordination, anxiolysis, and the elicitation of signs of physical dependence on withdrawal. We tested the hypothesis that the commonly abused solvents toluene, 1,1,1-trichloroethane (TCE), and trichloroethylene (TCY) affect ligand-gated ion channel activity, as do other classes of central nervous system-depressive agents. TCE and toluene, like ethanol, reversibly enhanced gamma-aminobutyric acid (GABA)(A) receptor-mediated synaptic currents in rat hippocampal slices. All three inhalants significantly and reversibly enhanced neurotransmitter-activated currents at alpha1beta1 GABA(A) and alpha1 glycine receptors expressed in Xenopus oocytes. We previously identified specific amino acids of glycine and GABA(A) receptor subunits mediating alcohol and volatile anesthetic enhancement of receptor function. Toluene, TCE, and TCY were tested on several glycine receptor mutants, some of which were insensitive to ethanol and/or enflurane. Toluene and TCY enhancement of glycine receptor function was seen in all these mutants. However, the potentiating effects of TCE were abolished in three mutants and enhanced in two, a pattern more akin to that seen with enflurane than ethanol. These data suggest that inhaled drugs of abuse affect ligand-gated ion channels, and that the molecular sites of action of these compounds may overlap with those of ethanol and the volatile anesthetics.

The elimination of sodium and potassium hydroxides from desiccated soda lime diminishes degradation of desflurane to carbon monoxide and sevoflurane to compound A but does not compromise carbon dioxide absorption.

UNLABELLED: Normal (hydrated) soda lime absorbent (approximately 95% calcium hydroxide [Ca(OH)2], the remaining 5% consisting of a mixture of sodium hydroxide [NaOH] and potassium hydroxide [KOH]) degrades sevoflurane to the nephrotoxin Compound A, and desiccated soda lime degrades desflurane, enflurane, and isoflurane to carbon monoxide (CO). We examined whether the bases in soda lime differed in their capacities to contribute to the production of these toxic substances by degradation of the inhaled anesthetics. Our results indicate that NaOH and KOH are the primary determinants of degradation of desflurane to CO and modestly augment production of Compound A from sevoflurane. Elimination of these bases decreases CO production 10-fold and decreases average inspired Compound A by up to 41%. These salutary effects can be achieved with only slight decreases in the capacity of the remaining Ca(OH)2 to absorb carbon dioxide. IMPLICATIONS: The soda lime bases used to absorb carbon dioxide from anesthetic circuits can degrade inhaled anesthetics to compounds such as carbon monoxide and the nephrotoxin, Compound A. Elimination of the bases sodium hydroxide and potassium hydroxide decreases production of these noxious compounds without materially decreasing the capacity of the remaining base, Ca(OH)2, to absorb carbon dioxide.

Changing from isoflurane to desflurane toward the end of anesthesia does not accelerate recovery in humans.

BACKGROUND: In an attempt to combine the advantage of the lower solubilities of new inhaled anesthetics with the lesser cost of older anesthetics, some clinicians substitute the former for the latter toward the end of anesthesia. The authors tried to determine whether substituting desflurane for isoflurane in the last 30 min of a 120-min anesthetic would accelerate recovery. METHODS: Five volunteers were anesthetized three times for 2 h using a fresh gas inflow of 2 l/min: 1.25 minimum alveolar concentration (MAC) desflurane, 1.25 MAC isoflurane, and 1.25 MAC isoflurane for 90 min followed by 30 min of desflurane concentrations sufficient to achieve a total of 1.25 MAC equivalent ("crossover"). Recovery from anesthesia was assessed by the time to respond to commands, by orientation, and by tests of cognitive function. RESULTS: Compared with isoflurane, the crossover technique did not accelerate early or late recovery (P > 0.05). Recovery from isoflurane or the crossover anesthetic was significantly longer than after desflurane (P < 0.05). Times to response to commands for isoflurane, the crossover anesthetic, and desflurane were 23 +/- 5 min (mean +/- SD), 21 +/- 5 min, and 11 +/- 1 min, respectively, and to orientation the times were 27 +/- 7 min, 25 +/- 5 min, and 13 +/- 2 min, respectively. Cognitive test performance returned to reference values 15-30 min sooner after desflurane than after isoflurane or the crossover anesthetic. Isoflurane cognitive test performance did not differ from that with the crossover anesthetic at any time. CONCLUSIONS: Substituting desflurane for isoflurane during the latter part of anesthesia does not improve recovery, in part because partial rebreathing through a semiclosed circuit limits elimination of isoflurane during the crossover period. Although higher fresh gas flow during the crossover period would speed isoflurane elimination, the amount of desflurane used and, therefore, the cost would increase.

In rats breathing from a nonrebreathing system, substitution of desflurane for isoflurane toward the end of anesthesia incompletely restores the time of recovery toward that of desflurane.

UNLABELLED: The lower solubility of desflurane allows a more rapid emergence from anesthesia than after anesthesia with the more soluble but less expensive anesthetic, isoflurane. Some practitioners use isoflurane for maintenance of anesthesia, crossing over to desflurane later in maintenance in an attempt to combine the cost-effectiveness of isoflurane with the rapid emergence from desflurane. We hypothesized that this maneuver would not accomplish its goals. Twenty-four male Sprague-Dawley rats received 1.2 minimum alveolar anesthetic concentration (MAC) of desflurane for the final 15, 30, or 60 min of a 2-h, 1.2-MAC isoflurane anesthetic in a nonrebreathing anesthesia system. We measured the time from cessation of anesthetic administration to the time each rat righted himself twice. Immediately after righting for the second time, we tested each rat's ability to remain atop a rotating rod (Rota-Rod) for 60 s continuously. Early (righting reflex) and late (Rota-Rod) recovery occurred more rapidly (P < 0.001) after 120 min of anesthesia with desflurane alone than after 120 min of anesthesia with isoflurane alone. A cross-over period of 30 min or longer produced a righting reflex time that did not differ from that found with desflurane alone, but a 15-min cross-over did not. Progressively longer cross-over periods led to proportionally better Rota-Rod performance, but no cross-over duration produced the rapidity of recovery seen with desflurane alone. We concluded that in a nonrebreathing system, switching to desflurane during the last 30 min of anesthesia substantially improved early recovery but produced a much smaller improvement in later recovery. IMPLICATIONS: The newer inhaled anesthetics offer the advantage of lower solubility, and thus more rapid emergence from anesthesia, than do the older inhaled anesthetics. However, they can be more expensive to use. This study demonstrates that substituting the newer anesthetic, desflurane, toward the end of anesthesia for an older anesthetic of greater solubility, isoflurane, does not produce recovery comparable to that of desflurane alone. Furthermore, this technique can be more costly than using desflurane throughout anesthesia.

Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury.

In susceptible patients, halothane, enflurane, isoflurane, and desflurane can produce severe hepatic injury by an immune response directed against reactive anesthetic metabolites covalently bound to hepatic proteins. The incidence of hepatotoxicity appears to directly correlate with anesthetic metabolism catalyzed by cytochrome P450 2E1 to trifluoroacetylated hepatic proteins. In the present study, we examined whether the extent of acylation of hepatic proteins in rats by halothane, enflurane, isoflurane, and desflurane correlated with reported relative rates of metabolism. After pretreatment with the P450 2E1 inducer isoniazid, five groups of 10 rats breathed 1.25 minimum alveolar anesthetic concentration (MAC) of halothane, enflurane, isoflurane, or desflurane in oxygen, or oxygen alone, each for 8 h. Immunochemical analysis of livers harvested 18 h after anesthetic exposure showed tissue acylation (greatest to least) after exposure to halothane, enflurane, or isoflurane. Reactivity was not different between isoflurane as compared to desflurane or oxygen alone. An enzyme-linked immunosorbent assay showed halothane reactivity was significantly greater than that of enflurane, isoflurane, desflurane, or oxygen, and that enflurane reactivity was significantly greater than desflurane or oxygen. Sera from patients with a clinical diagnosis of halothane hepatitis showed antibody reactivity against hepatic proteins from rats exposed to halothane or enflurane. No reactivity was detected in rats exposed to isoflurane, desflurane, or oxygen alone. These results indicate that production of acylated proteins may be an important mediator of anesthetic-induced hepatotoxicity.

Profound increase in viscosity and aggregation of pig gastric mucin at low pH.

Epithelial mucins are glycoproteins of very large molecular weight that provide viscoelastic and gel-forming properties to mucus, the jellylike protective layer covering epithelial organs. In the mammalian stomach the mucus gel layer protects the underlying epithelial cells from HCl in the lumen. We report here that pig gastric mucin undergoes a 100-fold increase in viscosity in vitro when pH is lowered from 7 to 2. Sedimentation velocity and dynamic light-scattering measurements revealed the formation of extremely large aggregates at low pH consistent with the observed increase in viscosity. Aggregation of mucin at low pH was prevented by increasing the ionic strength, suggesting the involvement of electrostatic interactions. Trypsin digestion and thiol reduction, but not enzymatic removal of neuraminic acid, prevented aggregation at low pH. This implies that the peptide core rather than the oligosaccharide side chains of the molecule is involved in the aggregation of mucin at low pH. Increased aggregation and viscosity at low pH were also observed in a solvent made to mimic the ionic composition of gastric juice, indicating the physiological relevance of our findings. Our observations suggest that one mechanism of gastric protection may be the ability of gastric mucin to undergo aggregation with a marked increase in viscosity at low pH.

Lipid binding to gastric mucin: protective effect against oxygen radicals.

Gastric mucus forms a viscous gel overlying the gastric mucosa and is thought to protect the underlying mucosa from noxious agents such as acid, proteases, and bile salts. A common property of mucin, the principal glycoprotein in mucous secretions, is its ability to bind lipids. The purpose of this study was to determine if lipids bound to gastric mucin protect the mucin from oxygen radical attack. Pig gastric mucin, partially purified by Sepharose 4B gel chromatography, was found to contain large amounts of free fatty acids and cholesterol as well as lesser amounts of sphingomyelin and phospholipids. Purified mucin obtained by density-gradient ultracentrifugation in a CsCl gradient contained only trace amounts of fatty acids but no other lipids. Exposure to the oxygen radical-generating system iron/ascorbate caused a marked reduction in viscosity of purified mucin but did not affect partially purified mucin, suggesting that bound lipids shielded the mucin from attack by oxygen radicals. Using discontinuous sucrose-gradient ultracentrifugation in the presence of liposomes containing [3H]palmitic acid, we demonstrated that mucin is capable of binding fatty acids. We also observed a striking increase in solution viscosity of gastric mucin at low pH, a feature that might contribute to the ability of mucin to form a protective diffusion barrier for the underlying epithelium.