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Sample records for isoflurane minimum alveolar

  1. Lidocaine, Dexmedetomidine and Their Combination Reduce Isoflurane Minimum Alveolar Concentration in Dogs

    PubMed Central

    Acevedo-Arcique, Carlos M.; Ibancovichi, José A.; Chavez, Julio R.; Gutierrez-Blanco, Eduardo; Moran-Muñoz, Rafael; Victoria-Mora, José M.; Tendillo-Cortijo, Francisco; Santos-González, Martín; Sanchez-Aparicio, Pedro

    2014-01-01

    The effects of intravenous (IV) lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI) on the minimum alveolar concentration of isoflurane (MACISO) in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MACISO/BASAL) was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI): lidocaine 2 mg kg−1, 100 µg kg−1 minute−1; dexmedetomidine 2 µg kg−1, 2 µg kg−1 hour−1; or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MACISO by 27.3% (range: 12.5–39.2%), 43.4% (33.3–53.3%) and 60.9% (46.1–78.1%), respectively, when compared to MACISO/BASAL. The combination resulted in a greater MACISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs. PMID:25232737

  2. Effect of Acetaminophen Alone and in Combination with Morphine and Tramadol on the Minimum Alveolar Concentration of Isoflurane in Rats

    PubMed Central

    Chavez, Julio R.; Ibancovichi, José A.; Sanchez-Aparicio, Pedro; Acevedo-Arcique, Carlos M.; Moran-Muñoz, Rafael; Recillas-Morales, Sergio

    2015-01-01

    Background It has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC. Methods Forty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MACISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg). Results The control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MACISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively. Conclusions The administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MACISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane. PMID:26605541

  3. Determination of minimum alveolar concentration of isoflurane in dogs and cats using the up-and-down method. A preliminary study.

    PubMed

    Barletta, Michele; Quandt, Jane; Hofmeister, Erik

    2016-06-01

    Minimum alveolar concentration (MAC) is a reliable measurement of the potency of inhaled anesthetic agents. The determination of MAC in different species has followed a fairly consistent methodology. In people, MAC is determined with the up-and-down method, whereas in animal the bracketing technique is commonly used. The objectives of this study were to determine the MAC value of isoflurane in dogs and cats using the up-and-down method and to determine the MAC value of isoflurane at extubation (MACex). General anesthesia was induced in 13 dogs and 5 cats with 5% isoflurane in oxygen. An initial end-tidal isoflurane concentration of 1.3% was used for the first dog and of 1.6% for the first cat and maintained constant for ≥20min. A noxious stimulus in the form of Carmalt forceps was applied to the base of the tail for no more than one minute or until movement was noticed. After stimulation, the response was recorded as positive (movement) or negative (no movement) and the animal was recovered. The end-tidal isoflurane concentration of the following animal was increased or decreased by 0.1% if the response of the previous animal to the stimulus was negative or positive, respectively. Isoflurane MAC values in dogs were 1.27% and 1.23%. Isoflurane MAC value in cats was 1.58%. MACex value was 0.45% in dogs and in cats. The up-and-down method for MAC determination achieved similar results when compared to MAC values of isoflurane in dogs and cats reported in the literature using the bracketing technique. PMID:27234540

  4. Increases in Spinal Cerebrospinal Fluid Potassium Concentration Do Not Increase Isoflurane Minimum Alveolar Concentration in Rats

    PubMed Central

    Shnayderman, Dimitry; Laster, Michael J.; Eger, Edmond I; Oh, Irene; Zhang, Yi; Jinks, Steven L.; Antognini, Joseph F.; Raines, Douglas E.

    2009-01-01

    BACKGROUND Previous studies demonstrated that MAC for isoflurane directly correlates with the concentration of Na+ in cerebrospinal fluid surrounding the spinal cord, the primary site for mediation of the immobility produced by inhaled anesthetics. If this correlation resulted from increased irritability of the cord, then infusion of increased concentrations of potassium (K+) might be predicted to act similarly. However, an absence of effect of K+ might be interpreted to indicate that K+ channels do not mediate the immobility produced by inhaled anesthetics whereas Na+ channels remain as potential mediators. Accordingly, in the present study, we examined the effect of altering intrathecal concentrations of K+ on MAC. METHODS In rats prepared with chronic indwelling intrathecal catheters, we infused solutions deficient in K+ and with an excess of K+ into the lumbar space and measured MAC for isoflurane 24 h before, during, and 24 h after infusion. Rats similarly prepared were tested for the effect of altered osmolarity on MAC (accomplished by infusion of mannitol) and for the penetration of Na+ into the cord. RESULTS MAC of isoflurane never significantly increased with increasing concentrations of K+ infused intrathecally. At infused concentrations exceeding 12 times the normal concentration of KCl, i.e., 29 mEq/L, rats moved spontaneously at isoflurane concentrations just below, and sometimes at MAC, but the average MAC in these rats did not exceed their control MAC. At the largest infused concentration (58.1 mEq/L), MAC significantly decreased and did not subsequently return to normal (i.e., such large concentrations produced injury). Infusions of lower concentrations of K+ had no effect on MAC. Infusion of osmotically equivalent solutions of mannitol did not affect MAC. Na+ infused intrathecally measurably penetrated the spinal cord. CONCLUSIONS The results do not support a mediation or modulation of MAC by K+ channels. PMID:18713900

  5. Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs.

    PubMed

    Ueyama, Yukie; Lerche, Phillip; Eppler, C Mark; Muir, William W

    2009-12-01

    OBJECTIVE-To determine the effects of IV administration of perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS-6 healthy sexually intact Beagles (3 males and 3 females). PROCEDURES-All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), perzinfotel (20 mg/kg, IV), fentanyl (5 microg/kg bolus, IV, followed by a continuous IV infusion at 0.15 microg/kg/min), and a fentanyl-perzinfotel combination (20 mg of perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia. RESULTS-Without treatment, the mean +/- SD isoflurane MAC for all 6 dogs was 1.41 +/- 0.10%. Baseline MAC was 1.42 +/- 0.08%. Intravenous administration of perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure. PMID:19951116

  6. Reduction of the minimum alveolar concentration of isoflurane in dogs using a constant rate of infusion of lidocaine-ketamine in combination with either morphine or fentanyl.

    PubMed

    Aguado, Delia; Benito, Javier; Gómez de Segura, Ignacio A

    2011-07-01

    The objective of this study was to determine the effects of a constant rate of infusion of lidocaine and ketamine in combination with either morphine or fentanyl on the minimum alveolar concentration of isoflurane (MAC(ISO)) during ovariohysterectomy in dogs. Female dogs (n=44) were premedicated with acepromazine and midazolam. Anaesthesia was induced with propofol and maintained with isoflurane. Dogs received ketamine (0.6 mg/kg/h) and lidocaine (3 mg/kg/h) together with morphine (0.24 mg/kg/h; MLK) or fentanyl (0.0036 mg/kg/h; FLK). The control group received Ringer's lactate solution. A skin incision was used as the noxious stimulus. The MAC(ISO) value was obtained with Dixon's up-and-down method. MAC(ISO) was 0.7±0.0 vol.% in the control group, 0.3±0.0 vol.% in the MLK group (45% MAC reduction) and 0.0±0.0 vol.% in the FLK group (97% MAC reduction). A combination of fentanyl with lidocaine and ketamine decreased the MAC(ISO) in dogs; this decrease was more pronounced than that produced by morphine, lidocaine and ketamine. PMID:20594878

  7. Effects of Methadone on the Minimum Anesthetic Concentration of Isoflurane, and Its Effects on Heart Rate, Blood Pressure and Ventilation during Isoflurane Anesthesia in Hens (Gallus gallus domesticus)

    PubMed Central

    Pypendop, Bruno Henri; Zangirolami Filho, Darcio; Sousa, Samuel Santos; Valadão, Carlos Augusto Araújo

    2016-01-01

    The aim of this study was to measure the temporal effects of intramuscular methadone administration on the minimum anesthetic concentration (MAC) of isoflurane in hens, and to evaluate the effects of the isoflurane-methadone combination on heart rate and rhythm, blood pressure and ventilation. Thirteen healthy adult hens weighing 1.7 ± 0.2 kg were used. The MAC of isoflurane was determined in each individual using the bracketing method. Subsequently, the reduction in isoflurane MAC produced by methadone (3 or 6 mg kg-1, IM) was determined by the up-and-down method. Stimulation was applied at 15 and 30 minutes, and at 45 minutes if the bird had not moved at 30 minutes. Isoflurane MAC reduction was calculated at each time point using logistic regression. After a washout period, birds were anesthetized with isoflurane and methadone, 6 mg kg-1 IM was administered. Heart rate and rhythm, respiratory rate, blood gas values and invasive blood pressure were measured at 1.0 and 0.7 isoflurane MAC, and during 45 minutes after administration of methadone once birds were anesthetized with 0.7 isoflurane MAC. Fifteen minutes after administration of 3 mg kg-1 of methadone, isoflurane MAC was reduced by 2 (-9 to 13)% [logistic regression estimate (95% Wald confidence interval)]. Administration of 6 mg kg-1 of methadone decreased isoflurane MAC by 29 (11 to 46)%, 27 (-3 to 56)% and 10 (-8 to 28)% after 15, 30 and 45 minutes, respectively. Methadone (6 mg kg-1) induced atrioventricular block in three animals and ventricular premature contractions in two. Methadone caused an increase in arterial blood pressure and arterial partial pressure of carbon dioxide, while heart rate and pH decreased. Methadone, 6 mg kg-1 IM significantly reduced isoflurane MAC by 30% in hens 15 minutes after administration. At this dose, methadone caused mild respiratory acidosis and increase in systemic blood pressure. PMID:27018890

  8. Combining isoflurane anesthesia with midazolam and butorphanol in rats.

    PubMed

    Tsukamoto, Atsushi; Uchida, Kaho; Maesato, Shizuka; Sato, Reiichiro; Kanai, Eiichi; Inomata, Tomo

    2016-07-29

    Representative inhalant anesthetic agent, isoflurane is commonly used during surgery in rats. However, isoflurane mediates relatively strong respiratory depression. In human and veterinary medicine, sedatives and analgesics are co-administered to complement the anesthetic action of inhalant anesthesia. The present study aimed to establish the novel balanced anesthesia that combines midazolam and butorphanol with isoflurane (MBI) in rats. Male Sprague Dawley rats were divided into 2 groups, and administered either isoflurane monoanesthesia or isoflurane with midazolam (2.5 mg/kg, ip) and butorphanol (2.0 mg/kg, ip). The minimum alveolar concentration (MAC) in each group was evaluated. Induction and recovery times were measured in each group. Adverse reactions during induction were also recorded. In each group, vital signs were assessed for 1 h under 1.5×MAC of isoflurane. Instability of vital signs was assessed under each anesthesia by calculating coefficient of variance. Compared with isoflurane monoanesthesia, MBI anesthesia caused 32% MAC reduction (isoflurane monoanesthesia: 1.30 ± 0.09%, MBI 0.87 ± 0.08%, P<0.05). MB premedication mediated smooth sedating action with low incidence of adverse reactions such as urination and defecation. Isoflurane monoanesthsesia remarkably decreased respiratory rate and saturation O2 (SPO2). In contrast, MBI anesthesia resulted in a relatively stable respiratory rate without decreases in SPO2 during the anesthetic period. In summary, MB premedication is effective for attenuating respiratory depression induced by isoflurane, and achieving smooth induction. This anesthetic protocol serves as a novel option for appropriate anesthesia in rats. PMID:26876437

  9. Combining isoflurane anesthesia with midazolam and butorphanol in rats

    PubMed Central

    Tsukamoto, Atsushi; Uchida, Kaho; Maesato, Shizuka; Sato, Reiichiro; Kanai, Eiichi; Inomata, Tomo

    2016-01-01

    Representative inhalant anesthetic agent, isoflurane is commonly used during surgery in rats. However, isoflurane mediates relatively strong respiratory depression. In human and veterinary medicine, sedatives and analgesics are co-administered to complement the anesthetic action of inhalant anesthesia. The present study aimed to establish the novel balanced anesthesia that combines midazolam and butorphanol with isoflurane (MBI) in rats. Male Sprague Dawley rats were divided into 2 groups, and administered either isoflurane monoanesthesia or isoflurane with midazolam (2.5 mg/kg, ip) and butorphanol (2.0 mg/kg, ip). The minimum alveolar concentration (MAC) in each group was evaluated. Induction and recovery times were measured in each group. Adverse reactions during induction were also recorded. In each group, vital signs were assessed for 1 h under 1.5×MAC of isoflurane. Instability of vital signs was assessed under each anesthesia by calculating coefficient of variance. Compared with isoflurane monoanesthesia, MBI anesthesia caused 32% MAC reduction (isoflurane monoanesthesia: 1.30 ± 0.09%, MBI 0.87 ± 0.08%, P<0.05). MB premedication mediated smooth sedating action with low incidence of adverse reactions such as urination and defecation. Isoflurane monoanesthsesia remarkably decreased respiratory rate and saturation O2 (SPO2). In contrast, MBI anesthesia resulted in a relatively stable respiratory rate without decreases in SPO2 during the anesthetic period. In summary, MB premedication is effective for attenuating respiratory depression induced by isoflurane, and achieving smooth induction. This anesthetic protocol serves as a novel option for appropriate anesthesia in rats. PMID:26876437

  10. Effect of midazolam and butorphanol premedication on inhalant isoflurane anesthesia in mice.

    PubMed

    Tsukamoto, Atsushi; Iimuro, Mami; Sato, Reiichiro; Yamazaki, Jumpei; Inomata, Tomo

    2015-01-01

    Isoflurane is a representative inhalant anesthesia used in laboratory animals. However, isoflurane mediates respiratory depression and adverse clinical reactions during induction. In the present study, we established a novel balanced anesthesia method in mice that combined isoflurane anesthesia with midazolam and butorphanol (MB). Thirty-four male C57BL/6J mice received either isoflurane alone or isoflurane with an intra-peritoneal MB premedication (3 mg/kg midazolam and 4 mg/kg butorphanol). The minimum alveolar concentration (MAC) in each group was evaluated. Induction time and adverse clinical reactions were recorded in each group. Core body temperature, heart rate, respiratory rate, and oxygen saturation (SPO(2)) were assessed before and for 1 h after induction. Premedication with MB achieved a significant reduction in MAC compared with isoflurane monoanesthesia (isoflurane, 1.38 ± 0.15%; isoflurane with MB, 0.78 ± 0.10%; P<0.05). Induction time was significantly shortened with MB premedication, and adverse reactions such as excitement or incontinence were observed less frequently. Furthermore, isoflurane anesthesia with MB premedication caused increase of respiratory rates compared to isoflurane monoanesthesia. No significant decrease of SPO(2) was observed in MBI anesthesia, while a decrease in SPO(2) was apparent with isoflurane monoanesthesia (baseline, 98.3% ± 1.1; 10 min after induction, 91.8 ± 6.4%; P<0.05). In conclusion, premedication with MB was effective for the mitigation of respiratory depression induced by isoflurane in mice, with rapid induction and fewer adverse clinical reactions. PMID:25736585

  11. Effect of midazolam and butorphanol premedication on inhalant isoflurane anesthesia in mice

    PubMed Central

    TSUKAMOTO, Atsushi; IIMURO, Mami; SATO, Reiichiro; YAMAZAKI, Jumpei; INOMATA, Tomo

    2015-01-01

    Isoflurane is a representative inhalant anesthesia used in laboratory animals. However, isoflurane mediates respiratory depression and adverse clinical reactions during induction. In the present study, we established a novel balanced anesthesia method in mice that combined isoflurane anesthesia with midazolam and butorphanol (MB). Thirty-four male C57BL/6J mice received either isoflurane alone or isoflurane with an intra-peritoneal MB premedication (3 mg/kg midazolam and 4 mg/kg butorphanol). The minimum alveolar concentration (MAC) in each group was evaluated. Induction time and adverse clinical reactions were recorded in each group. Core body temperature, heart rate, respiratory rate, and oxygen saturation (SPO2) were assessed before and for 1 h after induction. Premedication with MB achieved a significant reduction in MAC compared with isoflurane monoanesthesia (isoflurane, 1.38 ± 0.15%; isoflurane with MB, 0.78 ± 0.10%; P<0.05). Induction time was significantly shortened with MB premedication, and adverse reactions such as excitement or incontinence were observed less frequently. Furthermore, isoflurane anesthesia with MB premedication caused increase of respiratory rates compared to isoflurane monoanesthesia. No significant decrease of SPO2 was observed in MBI anesthesia, while a decrease in SPO2 was apparent with isoflurane monoanesthesia (baseline, 98.3% ± 1.1; 10 min after induction, 91.8 ± 6.4%; P<0.05). In conclusion, premedication with MB was effective for the mitigation of respiratory depression induced by isoflurane in mice, with rapid induction and fewer adverse clinical reactions. PMID:25736585

  12. Isoflurane Suppresses Stress-Enhanced Fear Learning in a Rodent Model of Posttraumatic Stress Disorder

    PubMed Central

    Rau, Vinuta; Oh, Irene; Laster, Michael; Eger, Edmond I; Fanselow, Michael S.

    2009-01-01

    Background A minority of patients who experience awareness and/or pain during surgery subsequently develop posttraumatic stress disorder. In a rodent model of posttraumatic stress disorder, stress-enhanced fear learning (SEFL), rats are pre-exposed to a stressor of 15 footshocks. Subsequent exposure to a single footshock produces an enhanced fear response. This effect is akin to sensitized reactions shown by some posttraumatic stress disorder patients to cues previously associated with the traumatic event. Methods We studied the effect of isoflurane and nitrous oxide on SEFL. Rats were exposed to the inhaled anesthetic during or after a 15-footshock stressor. Then rats were given a single footshock in a different environment. Their fear response was quantified in response to the 15-footshock and single-footshock environments. SEFL longevity was tested by placing a 90-day period between the 15 footshocks and the single footshock. In addition, the intensity of the footshock was increased to evaluate treatment effectiveness. Results Increasing isoflurane concentrations decreased SEFL when given during, but not after, the stressor. At 0.40 minimum alveolar concentration, isoflurane given during the stressor blocked SEFL 90 days later. A three-fold increase in the stressor intensity increased the isoflurane concentration required to block SEFL to no more than 0.67 minimum alveolar concentration. As with isoflurane, nitrous oxide suppressed SEFL at a similar minimum alveolar concentration fraction. Conclusions These results suggest that sufficient concentrations (perhaps 0.67 minimum alveolar concentration or less) of an inhaled anesthetic may prevent SEFL. PMID:19212264

  13. Comparison of tracheal extubation in patients deeply anesthetized with desflurane or isoflurane.

    PubMed

    Smith, I; Taylor, E; White, P F

    1994-10-01

    A randomized, single-blind study design was used to compare desflurane with isoflurane in 31 adults undergoing intraocular surgery to determine whether the lower blood:gas partition coefficient of desflurane would result in a more rapid emergence after endotracheal extubation of deeply anesthetized patients. A standardized general anesthetic technique was used, consisting of sufentanil, 0.25 microgram/kg, and propofol, 1.5 mg/kg, followed by either isoflurane (n = 15) or desflurane (n = 16) in an air/oxygen mixture. After the operation and reversal of residual neuromuscular block, spontaneous ventilation was reestablished and the patients' tracheas were extubated at equianesthetic concentrations of desflurane and isoflurane (i.e., approximately 1.4 times the minimum alveolar anesthetic concentration [MAC]). Spontaneous movements occurred 5.7 (+/- 2.4) and 8.7 min (+/- 3.1; P = 0.005) after extubation in the desflurane and isoflurane groups, respectively. Eye opening and orientation also occurred significantly earlier after desflurane compared to isoflurane. Patients receiving desflurane (versus isoflurane) were also able to be transferred from the operating room significantly earlier (10.4 +/- 3.7 vs 14.5 +/- 4.3 min, P = 0.01). Use of desflurane (versus isoflurane) was not associated with an increased incidence of coughing or airway irritation during the emergence period. However, use of desflurane did not significantly reduce the duration of the postanesthesia care unit (PACU) stay or alter later recovery events compared to isoflurane. In conclusion, the more rapid emergence would favor the use of desflurane when tracheal extubation during deep anesthesia is required. PMID:7943769

  14. Distinct long-term neurocognitive outcomes after equipotent sevoflurane or isoflurane anaesthesia in immature rats

    PubMed Central

    Ramage, T. M.; Chang, F. L.; Shih, J.; Alvi, R. S.; Quitoriano, G. R.; Rau, V.; Barbour, K. C.; Elphick, S. A.; Kong, C. L.; Tantoco, N. K.; Ben-Tzur, D.; Kang, H.; McCreery, M. S.; Huang, P.; Park, A.; Uy, J.; Rossi, M. J.; Zhao, C.; Di Geronimo, R. T.; Stratmann, G.; Sall, J. W.

    2013-01-01

    Background Many anaesthetics when given to young animals cause cell death and learning deficits that persist until much later in life. Recent attempts to compare the relative safety or toxicity between different agents have not adequately controlled for the relative dose of anaesthetic given, thereby making direct comparisons difficult. Methods Isoflurane or sevoflurane were given at 1 minimum alveolar concentration (MAC) for 4 h to postnatal day 7 (P7) rat pups. Beginning at P75 these animals underwent fear conditioning and at P83 Morris water maze testing to assess working memory, short-term memory and early long-term memory using delays of 1 min, 1 h, and 4 h. Results No difference between groups was seen in fear conditioning experiments. Morris water maze learning was equivalent between groups, and no difference was seen in working memory. Sevoflurane-treated animals had a deficit in early long-term memory, and isoflurane-treated animals had a deficit in both short-term and early long-term memory. Conclusions Both isoflurane and sevoflurane delivered at 1 MAC for 4 h to immature rats caused a deficit in long-term memory. Isoflurane also caused a deficit in short-term memory. Isoflurane might be more detrimental than sevoflurane in very young animals. PMID:23592692

  15. Anesthesia with Isoflurane and Sevoflurane in the Crested Serpent Eagle (Spilornis cheela hoya): Minimum Anesthetic Concentration, Physiological Effects, Hematocrit, Plasma Chemistry and Behavioral Effects

    PubMed Central

    CHAN, Fang-Tse; CHANG, Geng-Ruei; WANG, Hsien-Chi; HSU, Tien-Huan

    2013-01-01

    ABSTRACT The initial goal of this study was to determine the minimum anesthetic concentration (MAC) for isoflurane (ISO) and sevoflurane (SEVO) for the crested serpent eagle. Next, we compared the anesthetic effects of each on the physiological effects, hematocrit, plasma chemistry values and behavior in spontaneously breathing captive adult crested serpent eagles. Sixteen eagles were randomly allocated to two groups for anesthesia with ISO (n=8) or SEVO (n=8). First, we measured the MAC values of ISO and SEVO, and four weeks later, we investigated the effect of each on the physiological effects, hematocrit (HCT) and plasma chemistry values. The MAC values of ISO and SEVO for crested serpent eagles were 1.46 ± 0.30 and 2.03 ± 0.32%, respectively. The results revealed no significant differences between the two anesthetics in induction time, while time of extubation to recovery was significantly shorter with SEVO. A time-related increase in end-tidal CO2 and decreases in body temperature and respiratory rates were observed during anesthesia with each anesthetic. There were no significant differences between the effect of the two anesthetics on heart rate, hematocrit, plasma chemistry values or respiration, although each caused minor respiration depression. We concluded that SEVO is a more effective inhalant agent than ISO for use in eagles, showing the most rapidest induction and recovery from anesthesia. PMID:23955396

  16. Effects of ketamine and lidocaine in combination on the sevoflurane minimum alveolar concentration in alpacas.

    PubMed

    Queiroz-Williams, Patricia; Doherty, Thomas J; da Cunha, Anderson F; Leonardi, Claudia

    2016-04-01

    This study investigated the effects of ketamine and lidocaine in combination on the minimum alveolar concentration of sevoflurane (MACSEVO) in alpacas. Eight healthy, intact male, adult alpacas were studied on 2 separate occasions. Anesthesia was induced with SEVO, and baseline MAC (MACB) determination began 45 min after induction. After MACB determination, alpacas were randomly given either an intravenous (IV) loading dose (LD) and infusion of saline or a loading dose [ketamine = 0.5 mg/kg body weight (BW); lidocaine = 2 mg/kg BW] and an infusion of ketamine (25 μg/kg BW per minute) in combination with lidocaine (50 μg/kg BW per minute), and MACSEVO was re-determined (MACT). Quality of recovery, time-to-extubation, and time-to-standing, were also evaluated. Mean MACB was 1.88% ± 0.13% and 1.89% ± 0.14% for the saline and ketamine + lidocaine groups, respectively. Ketamine and lidocaine administration decreased (P < 0.05) MACB by 57% and mean MACT was 0.83% ± 0.10%. Saline administration did not change MACB. Time to determine MACB and MACT was not significantly different between the treatments. The quality of recovery, time-to-extubation, and time-to-standing, were not different between groups. The infusion of ketamine combined with lidocaine significantly decreased MACSEVO by 57% and did not adversely affect time-to-standing or quality of recovery. PMID:27127341

  17. Effects of Lidocaine, Dexmedetomidine or Their Combination on the Minimum Alveolar Concentration of Sevoflurane in Dogs

    PubMed Central

    MORAN-MUÑOZ, Rafael; IBANCOVICHI, J. A.; Gutierrez-BLANCO, Eduardo; ACEVEDO-ARCIQUE, Carlos M.; Victoria MORA, J. Mauro; TENDILLO, Francisco J.; SANTOS-GONZALEZ, Martin; YAMASHITA, Kazuto

    2014-01-01

    ABSTRACT The aim of this study was to determine the effects of lidocaine (LIDO) and dexmedetomidine (DEX) or their combination (LIDO–DEX), administered by constant-rate infusion (CRI), on the minimum alveolar concentration (MAC) of sevoflurane in dogs. Seven healthy mongrel dogs were used with a 2-week washout interval between treatments in this study. Anesthesia was induced with propofol and maintained with sevoflurane in oxygen, and MAC of sevoflurane was determined after 90 min equilibration period in the dogs (SEV-MACBASAL). Then, sevoflurane MAC was determined again in the dogs after 45 min equilibration period of one of the following treatments: an intravenous loading dose of lidocaine 2 mg/kg followed by 6 mg/kg/hr CRI (SEV-MACLIDO); an intravenous loading dose of dexmedetomidine 2 µg/kg followed by 2 µg/kg/hr CRI (SEV-MACDEX); or their combination (SEV-MACLIDO-DEX). These SEV-MACs were determined in duplicate. Data were analyzed using ANOVA and post hoc Tuckey test when appropriate. The SEV-MACBASAL was 1.82 ± 0.06%, SEV-MACLIDO was 1.38 ± 0.08%, SEV-MACDEX was 1.22 ± 0.10%, and SEV-MACLIDO-DEX was 0.78 ± 0.06%. The CRI administration of lidocaine, dexmedetomidine and their combination produced a significant reduction in the MAC of sevoflurane by 26.1 ± 9.0% (P<0.0001), 43.7 ± 11.8% (P<0.0002) and 54.4 ± 9.8% (P<0.0001), respectively. The MAC reduction was significantly greater after the CRI combination of lidocaine and dexmedetomidine when compared with lidocaine CRI (P<0.0001) or dexmedetomidine CRI treatments (P<0.025). PMID:24572631

  18. Pulse pressure variation and stroke volume variation under different inhaled concentrations of isoflurane, sevoflurane and desflurane in pigs undergoing hemorrhage

    PubMed Central

    Oshiro, Alexandre Hideaki; Otsuki, Denise Aya; Hamaji, Marcelo Waldir M; Rosa, Kaleizu T; Ida, Keila Kazue; Fantoni, Denise T; Auler, José Otavio Costa

    2015-01-01

    OBJECTIVES: Inhalant anesthesia induces dose-dependent cardiovascular depression, but whether fluid responsiveness is differentially influenced by the inhalant agent and plasma volemia remains unknown. The aim of this study was to compare the effects of isoflurane, sevoflurane and desflurane on pulse pressure variation and stroke volume variation in pigs undergoing hemorrhage. METHODS: Twenty-five pigs were randomly anesthetized with isoflurane, sevoflurane or desflurane. Hemodynamic and echocardiographic data were registered sequentially at minimum alveolar concentrations of 1.00 (M1), 1.25 (M2), and 1.00 (M3). Then, following withdrawal of 30% of the estimated blood volume, these data were registered at a minimum alveolar concentrations of 1.00 (M4) and 1.25 (M5). RESULTS: The minimum alveolar concentration increase from 1.00 to 1.25 (M2) decreased the cardiac index and increased the central venous pressure, but only modest changes in mean arterial pressure, pulse pressure variation and stroke volume variation were observed in all groups from M1 to M2. A significant decrease in mean arterial pressure was only observed with desflurane. Following blood loss (M4), pulse pressure variation, stroke volume variation and central venous pressure increased (p<0.001) and mean arterial pressure decreased in all groups. Under hypovolemia, the cardiac index decreased with the increase of anesthesia depth in a similar manner in all groups. CONCLUSION: The effects of desflurane, sevoflurane and isoflurane on pulse pressure variation and stroke volume variation were not different during normovolemia or hypovolemia. PMID:26735220

  19. Effects of magnesium sulfate and propofol on the minimum alveolar concentration preventing motor movement in sevoflurane-anesthetized dogs.

    PubMed

    Johnson, Alanna N; Seddighi, Reza; Rohrbach, Barton W; Cox, Sherry K; Egger, Christine M; Martin-Flores, Manuel; Doherty, Thomas J

    2016-06-01

    OBJECTIVE To evaluate the effect of MgSO4, alone and in combination with propofol, on the minimum alveolar concentration preventing motor movement (MACNM) in sevoflurane-anesthetized dogs. ANIMALS 6 healthy purpose-bred adult male Beagles (least squares mean ± SEM body weight, 12.0 ± 1.1 kg). PROCEDURES Dogs were anesthetized 3 times at weekly intervals. The MACNM was measured 45 minutes after induction of anesthesia (baseline; MACNM-B) and was determined each time by use of a noxious electrical stimulus. Treatments were administered as a loading dose and constant rate infusion (CRI) as follows: treatment 1, MgSO4 loading dose of 45 mg/kg and CRI of 15 mg/kg/h; treatment 2, propofol loading dose of 4 mg/kg and CRI of 9 mg/kg/h; and treatment 3, MgSO4 and propofol combination (same doses used previously for each drug). A mixed-model ANOVA and Tukey-Kramer tests were used to determine effects of each treatment on the percentage decrease from MACNM-B. Data were reported as least squares mean ± SEM values. RESULTS Decrease from MACNM-B was 3.4 ± 3.1%, 48.3 ± 3.1%, and 50.3 ± 3.1%, for treatments 1, 2, and 3, respectively. The decrease for treatments 2 and 3 was significantly different from that for treatment 1; however, no significant difference existed between results for treatments 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE MgSO4 did not affect MACNM, nor did it potentiate the effects of propofol on MACNM. Administration of MgSO4 in this study appeared to provide no clinical advantage as an anesthetic adjuvant. PMID:27227494

  20. In Vitro Induction of Endothelial Apoptosis of the Post-Hypoxic Blood-Brain Barrier by Isoflurane but Not by Sevoflurane and Midazolam

    PubMed Central

    Dittmar, Michael S.; Petermichl, Walter; Lindner, Regina; Sinner, Barbara; Graf, Bernhard M.; Schlachetzki, Felix; Gruber, Michael

    2015-01-01

    Background The effects of anesthetics on the injured brain continue to be the subject of controversial discussion. Since isoflurane has recently been shown to induce apoptosis of cerebral endothelial cells, this study compared different anesthetic compounds regarding their potential to induce cerebro-vascular apoptosis. Methods The in vitro model of the blood-brain barrier used in this study consisted of astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVEC) has been used. After 24 h of deep hypoxia and reoxygenation or control treatment, AC-HUVEC were exposed to 0, 0.5, 1.0, or 2.0 times the minimum alveolar concentration of isoflurane or sevoflurane, or 0, 75, 150, or 300 nM of midazolam for 2 h. After 24 h, AC-HUVEC were harvested, and the degree of apoptosis was assessed by means of Western blots for the Bax and Bcl-2 ratio and, for controls and the highest concentration groups, terminal deoxynucleotidyl-mediated dUTP-biotin nick end labeling (TUNEL). Results Without hypoxic pretreatment, 2.0 MAC of isoflurane slightly increased TUNEL intensity compared to control and sevoflurane, but without any significant changes in the Bax and Bcl-2 ratio. After hypoxic pretreatment, exposure to isoflurane led to a multifold increase in the Bax and Bcl-2 ratio in a dose dependent manner, which was also significantly higher than the ratio observed in the 2 MAC sevoflurane group. TUNEL intensity in the post-hypoxic 2 MAC isoflurane group was increased by a factor of 11 vs. control and by 40 vs. sevoflurane. Sevoflurane and midazolam did not significantly alter these markers of apoptosis, when compared to the control group. Conclusions Isoflurane administered after hypoxia elevates markers of apoptosis in endothelial cells transdifferentiated to the cerebro-vascular endothelium. Endothelial apoptosis may be a previously underestimated mechanism of anesthetic neurotoxicity. Administration of high concentrations of isoflurane in experimental settings may have

  1. The anesthetic interaction of propofol and sevoflurane on the minimum alveolar concentration preventing motor movement (MACNM) in dogs.

    PubMed

    Singsank-Coats, Jill; Seddighi, Reza; Rohrbach, Barton W; Cox, Sherry K; Egger, Christine M; Doherty, Thomas J

    2015-04-01

    The objective of this study was to determine the effects of propofol on the minimum alveolar concentration of sevoflurane needed to prevent motor movement (MAC(NM)) in dogs subjected to a noxious stimulus using randomized crossover design. Six, healthy, adult beagles (9.2 ± 1.3 kg) were used. Dogs were anesthetized with sevoflurane on 3 occasions, at weekly intervals, and baseline MAC(NM) (MAC(NM-B)) was determined on each occasion. Propofol treatments were administered as loading dose (LD) and constant rate infusion (CRI) as follows: Treatment 1 (T1) was 2 mg/kg body weight (BW) and 4.5 mg/kg BW per hour; T2 was 4 mg/kg BW and 9 mg/kg BW per hour; T3 was 8 mg/kg BW and 18 mg/kg BW per hour, respectively. Treatment MAC(NM) (MAC(NM-T)) determination was initiated 60 min after the start of the CRI. Two venous blood samples were collected and combined at each MAC(NM-T) determination for measurement of blood propofol concentration using high-performance liquid chromatography method (HPLC). Data were analyzed using a mixed-model ANOVA and are presented as least square means (LSM) ± standard error of means (SEM). Propofol infusions in the range of 4.5 to 18 mg/kg BW per hour resulted in mean blood concentrations between 1.3 and 4.4 μg/mL, and decreased (P < 0.05) sevoflurane MAC(NM) in a concentration-dependent manner. The percentage decrease in MAC(NM) was 20.5%, 43.0%, and 68.3%, with corresponding blood propofol concentrations of 1.3 ± 0.3 μg/mL, 2.5 ± 0.3 μg/mL, and 4.4 ± 0.3 μg/mL, for T1, T2, and T3, respectively. Venous blood propofol concentrations were strongly correlated (r = 0.855, P < 0.0001) with the decrease in MAC(NM). In dogs, propofol decreased the sevoflurane MAC(NM) in a concentration-dependent manner. PMID:25852224

  2. A brief exposure to isoflurane (50 s) significantly impacts on plasma cytokine levels in endotoxemic rats.

    PubMed

    Hofstetter, Christian; Flondor, Michael; Boost, Kim A; Koehler, Patricia; Bosmann, Markus; Pfeilschifter, Josef; Zwissler, Bernhard; Mühl, Heiko

    2005-09-01

    Induction of anesthesia by inhalation of isoflurane is a frequently used procedure in models of immunological diseases. Here we investigated effects of a brief exposure to isoflurane on cytokine production by endotoxemic rats. Anesthesia was either performed by pentobarbital/fentanyl without or accompanied by a 50-s inhalation pretreatment with isoflurane. After 4 h of endotoxemia, plasma levels of TNFalpha, IL-1beta, and RANTES were determined. Isoflurane significantly inhibited plasma levels of TNFalpha and IL-1beta by 69.3% and 61.8%, respectively. Levels of RANTES were similarly reduced by 43.1% (n.s.). Moreover, isoflurane significantly attenuated basal nitrite production by alveolar macrophages isolated from endotoxemic rats (by 59.4%). Thus, we confirm anti-inflammatory properties of isoflurane and beyond that clearly demonstrate that even a short exposure (<1 min) can profoundly affect pro-inflammatory parameters in experimental endotoxemia. These unforeseen observations suggest that short-term inhalation of isoflurane for induction of anesthesia may be an unsuitable procedure particularly in animal models of acute inflammation. PMID:16023603

  3. Guided isoflurane injection in a totally closed circuit.

    PubMed

    el-Attar, A M

    1991-12-01

    Twenty-six patients undergoing middle ear surgery were anaesthetised using a completely closed circuit into which liquid isoflurane was injected using a syringe pump. The injection rate was guided by a table of calculated rates of isoflurane uptake, utilising the square root of time principle, at succeeding time intervals in different weight groups. A constant alveolar concentration of 1.3 MAC was aimed for. The injection rate was changed to that for the higher or lower weight group appropriate to the time interval whenever clinical signs indicated inappropriate depth of anaesthesia. A mean of 10.3 ml liquid isoflurane was used to maintain anaesthesia for a mean of 82.3 minutes. Blood pressure was maintained at 75% of the pre-operative value. Mean arterial blood gas data and changes in plasma catecholamine levels were within the normal range. The mean recovery time was 10.5 minutes. Syringe pump delivery of liquid isoflurane avoided fluctuations that result from bolus injections of unit dose. The implemented injection rate table, working as a therapeutic window, guided redosing, reduced calculation time and served as a record. The technique is safe, economic and adaptable to variations in uptake and response to inhalational anaesthetics. PMID:1781534

  4. 21 CFR 529.1186 - Isoflurane.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Amount—(i) Horses: For induction of surgical anesthesia: 3 to 5 percent isoflurane (with oxygen) for 5 to 10 minutes. For maintenance of surgical anesthesia: 1.5 to 1.8 percent isoflurane (with oxygen). (ii) Dogs: For induction of surgical anesthesia: 2 to 2.5 percent isoflurane (with oxygen) for 5 to...

  5. 21 CFR 529.1186 - Isoflurane.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... inhalation: (1) Amount—(i) Horses: For induction of surgical anesthesia: 3 to 5 percent isoflurane (with oxygen) for 5 to 10 minutes. For maintenance of surgical anesthesia: 1.5 to 1.8 percent isoflurane (with oxygen). (ii) Dogs: For induction of surgical anesthesia: 2 to 2.5 percent isoflurane (with oxygen) for...

  6. 21 CFR 529.1186 - Isoflurane.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Amount—(i) Horses: For induction of surgical anesthesia: 3 to 5 percent isoflurane (with oxygen) for 5 to 10 minutes. For maintenance of surgical anesthesia: 1.5 to 1.8 percent isoflurane (with oxygen). (ii) Dogs: For induction of surgical anesthesia: 2 to 2.5 percent isoflurane (with oxygen) for 5 to...

  7. 21 CFR 529.1186 - Isoflurane.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... inhalation: (1) Amount—(i) Horses: For induction of surgical anesthesia: 3 to 5 percent isoflurane (with oxygen) for 5 to 10 minutes. For maintenance of surgical anesthesia: 1.5 to 1.8 percent isoflurane (with oxygen). (ii) Dogs: For induction of surgical anesthesia: 2 to 2.5 percent isoflurane (with oxygen) for...

  8. 21 CFR 529.1186 - Isoflurane.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... inhalation: (1) Amount—(i) Horses: For induction of surgical anesthesia: 3 to 5 percent isoflurane (with oxygen) for 5 to 10 minutes. For maintenance of surgical anesthesia: 1.5 to 1.8 percent isoflurane (with oxygen). (ii) Dogs: For induction of surgical anesthesia: 2 to 2.5 percent isoflurane (with oxygen) for...

  9. Azi-isoflurane, a Photolabel Analog of the Commonly Used Inhaled General Anesthetic Isoflurane

    PubMed Central

    2009-01-01

    Volatility and low-affinity hamper an ability to define molecular targets of the inhaled anesthetics. Photolabels have proven to be a useful approach in this regard, although none have closely mimicked contemporary drugs. We report here the synthesis and validation of azi-isoflurane, a compound constructed by adding a diazirinyl moiety to the methyl carbon of the commonly used general anesthetic isoflurane. Azi-isoflurane is slightly more hydrophobic than isoflurane, and more potent in tadpoles. This novel compound inhibits Shaw2 K+ channel currents similarly to isoflurane and binds to apoferritin with enhanced affinity. Finally, when irradiated at 300 nm, azi-isoflurane adducts to residues known to line isoflurane-binding sites in apoferritin and integrin LFA-1, the only proteins with isoflurane binding sites defined by crystallography. This reagent should allow rapid discovery of isoflurane molecular targets and binding sites within those targets. PMID:20228895

  10. Isoflurane ameliorates acute lung injury by preserving epithelial tight junction integrity

    PubMed Central

    Englert, Joshua A.; Macias, Alvaro A.; Amador-Munoz, Diana; Vera, Miguel Pinilla; Isabelle, Colleen; Guan, Jiazhen; Magaoay, Brady; Velandia, Margarita Suarez; Coronata, Anna; Lee, Awapuhi; Fredenburgh, Laura E.; Culley, Deborah J.; Crosby, Gregory; Baron, Rebecca M.

    2015-01-01

    Background Isoflurane may be protective in pre-clinical models of lung injury but its use in patients with lung injury remains controversial and the mechanism of its protective effects remains unclear. We hypothesized that this protection is mediated at the level of alveolar tight junctions and investigated the possibility in a two-hit model of lung injury that mirrors human acute respiratory distress syndrome. Methods Wild-type mice were treated with isoflurane one hour after exposure to nebulized endotoxin (n=8) or saline control (n=9) then allowed to recover for 24 hrs prior to mechanical ventilation (MV, tidal volume 15 mL/kg, 2 hrs) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane one hour after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo. Results Mice treated with isoflurane following exposure to inhaled endotoxin and prior to MV exhibited significantly less physiologic lung dysfunction. These effects appeared to be mediated by decreased vascular leak, but not altered inflammatory indices. Mouse lung epithelial cells treated with lipopolysaccharide and cyclic stretch and lungs harvested from mice following treatment with lipopolysaccharide and MV had decreased levels of a key tight junction protein (i.e. zona occludens 1) that was rescued by isoflurane treatment. Conclusions Isoflurane rescued lung injury induced by a two-hit model of endotoxin exposure followed by MV by maintaining the integrity of the alveolar-capillary barrier possibly by modulating the expression of a key tight junction protein. PMID:26068207

  11. Anesthetic potency and cardiopulmonary effects of sevoflurane in goats: comparison with isoflurane and halothane.

    PubMed Central

    Hikasa, Y; Okuyama, K; Kakuta, T; Takase, K; Ogasawara, S

    1998-01-01

    The anesthetic potency and cardiopulmonary effects of sevoflurane were compared with those of isoflurane and halothane in goats. The (mean +/- SD) minimal alveolar concentration (MAC) was 0.96 +/- 0.12% for halothane, 1.29 +/- 0.11% for isoflurane, and 2.33 +/- 0.15% for sevoflurane. Cardiopulmonary effects of sevoflurane, halothane and isoflurane were examined at end-tidal concentrations equivalent to 1, 1.5 and 2 MAC during either spontaneous or controlled ventilation (SV or CV). During SV, there were no significant differences in respiration rate, tidal volume and minute ventilation between anesthetics. Dose-dependent decreases in both tidal volume and minute ventilation induced by halothane were greater than those by either sevoflurane or isoflurane. Hypercapnia and acidosis induced by sevoflurane were not significantly different from those by either isoflurane or halothane at 1 and 1.5 MAC, but were less than those by halothane at 2 MAC. There was no significant difference in heart rate between anesthetics during SV and CV. During SV, all anesthetics induced dose-dependent decreases in arterial pressure, rate pressure product, systemic vascular resistance, left ventricular minute work index and left ventricular stroke work index. Systemic vascular resistance with isoflurane at 2 MAC was lower than that with sevoflurane. During CV, sevoflurane induced dose-dependent circulatory depression (decreases in arterial pressure, cardiac index, rate pressure product, systemic vascular resistance, left ventricular minute work index and right ventricular minute work index), similar to isoflurane. Halothane did not significantly alter systemic vascular resistance from 1 to 2 MAC. PMID:9798097

  12. Effects of isoflurane and sevoflurane on the neutrophil myeloperoxidase system of horses.

    PubMed

    Minguet, Grégory; Franck, Thierry; Joris, Jean; Ceusters, Justine; Mouithys-Mickalad, Ange; Serteyn, Didier; Sandersen, Charlotte

    2015-05-15

    Volatile anaesthestics have shown to modulate the oxidative response of polymorphonuclear neutrophils (PMNs). We investigated the effects of isoflurane and sevoflurane on the degranulation of total and active myeloperoxidase (MPO) from horse PMNs and their direct interaction with MPO activity. Whole blood from horse was incubated in 1 and 2 minimal alveolar concentrations (MAC) of isoflurane or sevoflurane for 1h and PMNs were stimulated with cytochalasin B (CB) plus N-formyl-méthionyl-leucyl-phenylalanine (fMLP). After stimulation, the plasma was collected to measure total and active MPO by enzyme-linked immunosorbent assay (ELISA) and specific immunological extraction followed by enzymatic detection (SIEFED) respectively. The effects of 1 and 2 MAC of isoflurane and sevoflurane on the peroxidase and chlorination activity of pure MPO were assessed by fluorescence using Amplex red and 3'-(p-aminophenyl) fluorescein (APF) respectively and in parallel with a SIEFED assay to estimate the potential interaction of the anaesthetics with the enzyme. Although isoflurane and sevoflurane had inconsistent effects on total MPO release, both volatile agents reduced active MPO release and showed a direct inhibition on the peroxidase and the chlorination activity of the enzyme. A persistent interaction between MPO and anaesthetics was evidenced with isoflurane but not with sevoflurane. PMID:25796094

  13. Isoflurane Postconditioning Protects Against Reperfusion Injury by Preventing Mitochondrial Permeability Transition via an Endothelial Nitric Oxide Synthase-dependent Mechanism

    PubMed Central

    Ge, Zhi-Dong; Pravdic, Danijel; Bienengraeber, Martin; Pratt, Phillip F.; Auchampach, John A.; Gross, Garrett J.; Kersten, Judy R.; Warltier, David C.

    2015-01-01

    Background The role of endothelial nitric oxide synthase (eNOS) in isoflurane postconditioning (IsoPC)-elicited cardioprotection is poorly understood. We addressed this issue using eNOS-/- mice. Methods In vivo or Langendorff-perfused mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion in the presence and absence of postconditioning produced with isoflurane 5 min before ischemia and 3 min after reperfusion. Ca2+-induced mitochondrial permeability transition pore opening was assessed in isolated mitochondria. Echocardiography was used to evaluate ventricular function. Results Postconditioning with 0.5, 1.0, and 1.5 minimum alveolar concentrations of isoflurane decreased infarct size from 56 ± 10% (n = 10) in control to 48 ± 10%, 41 ± 8% (n = 8, P < 0.05), and 38 ± 10% (n = 8, P < 0.05), respectively and improved cardiac function in wild-type mice. Improvement in cardiac function by IsoPC was blocked by NG-nitro-L-arginine methyl ester (a nonselective NOS inhibitor) administered either prior to ischemia or at the onset of reperfusion. Mitochondria isolated from postconditioned hearts required significantly higher in vitro Ca2+ loading than control (78 ± 29 vs. 40 ± 25 μM CaCl2 mg protein-1, n = 10, P < 0.05) to open the mitochondrial permeability transition pore. Hearts from eNOS-/- mice displayed no marked differences in infarct size, cardiac function, and sensitivity of mitochondrial permeability transition pore to Ca2+, compared to the wild-type hearts. However, IsoPC failed to alter infarct size, cardiac function or the amount of Ca2+ necessary to open the mitochondrial permeability transition pore in mitochondria isolated from the eNOS-/- hearts compared to control hearts. Conclusions IsoPC protects mouse hearts from reperfusion injury by preventing MPT pore opening in an eNOS-dependent manner. Nitric oxide functions as both a trigger and a mediator of cardioprotection produced by IsoPC. PMID:19996950

  14. Overpressure isoflurane at caesarean section: a study of arterial isoflurane concentrations.

    PubMed

    McCrirrick, A; Evans, G H; Thomas, T A

    1994-01-01

    In this study we have measured arterial concentrations of isoflurane obtained during Caesarean section in two groups of patients. Patients in group 1 received 1% isoflurane throughout operation, whilst those in group 2 received 2% isoflurane for the first 5 min, 1.5% for the next 5 min and 0.8% thereafter. We found that arterial isoflurane concentrations were significantly greater in group 2 than in group 1 (ANOVA, P < 0.05). Isoflurane concentrations greater than 30 micrograms ml-1 were achieved rapidly in most patients in both groups, but there was a large scatter of results. The isoflurane concentration at which awareness or recall may occur is not known, but an "overpressure" technique as described for patients in group 2 may result in fewer patients being at risk of awareness. PMID:8110537

  15. Absorption of isoflurane by silica gel.

    PubMed

    Lumb, A B; Landon, M J

    1991-07-01

    We have studied the capacity of the drying agent silica gel (SG) to absorb isoflurane from gas samples. When dry, SG was able to absorb 31 times its own volume of isoflurane vapour, which could be recovered almost completely from the SG by displacement with water vapour. However, we were unable to demonstrate any significant absorption of isoflurane by wet SG. Care must be taken, therefore, when using SG as a drying agent in the sampling line of an analyser during research involving volatile anaesthetic agents. PMID:1650238

  16. Ventricular arrhythmogenic dose of adrenaline during sevoflurane, isoflurane, and halothane anaesthesia either with or without ketamine or thiopentone in cats.

    PubMed

    Hikasa, Y; Okabe, C; Takase, K; Ogasawara, S

    1996-03-01

    The doses of adrenaline required to induce ventricular arrhythmia during sevoflurane, isoflurane and halothane anaesthesia, either with or without infusions of ketamine (76 micrograms kg-1 min-1) or thiopentone (0.5 mg kg-1 min-1), were determined in cats. Groups of six to eight cats were maintained at end-tidal concentrations equivalent to 1.25 times the minimal alveolar concentration of each anaesthetic. The mean dose of adrenaline required to induce arrhythmia during sevoflurane anaesthesia (19.0 micrograms kg-1) was approximately 11 times higher than that required during halothane anaesthesia (1.66 micrograms kg-1) and the same as that required during isoflurane anaesthesia (19.0 micrograms kg-1). Ketamine tended to decrease the requirement of adrenaline during halothane anaesthesia, but not significantly, and did not change the requirement during isoflurane or sevoflurane anaesthesia. Thiopentone did not change the requirement for adrenaline during halothane, isoflurane or sevoflurane anaesthesia. It was concluded that either with or without ketamine or thiopentone, the effect of sevoflurane on the sensitisation of the feline myocardium to the arrhythmogenic effects of adrenaline was significantly less than that of halothane and not different from that of isoflurane. PMID:8685534

  17. [Pulmonary alveolar proteinosis].

    PubMed

    Hutyrová, B

    2007-10-01

    Pulmonary alveolar proteinosis is a rare disease characterised by excessive accumulation of surfactant components in the alveoli and the distal airways with minimum inflammatory reaction and fibrosis of pulmonary interstitium. Three clinical forms of pulmonary alveolar proteinosis are distinguished - congenital, primary and secondary. Results of ultrastructural, biochemical and functional analyses and studies performed on genetically modified mice support the presumption that accumulation of surfactant in pulmonary alveolar proteinosis is a result of a degradation disorder and of diminished clearance of the surfactant from the alveolar space rather than of excessive synthesis of surfactant components. Over the last 15 years, significant discoveries have been made which have helped to clarify the etiology and pathogenesis of the disease. A number of gene mutations have been discovered which lead to the development of congenital pulmonary proteinosis. Apart from impaired surfactant protein function, a key role in the development of pulmonary alveolar proteinosis is played by the signal pathway of granulocyte and macrophage colonies stimulating growth factor (GM-CSF) which is necessary for the functioning of alveolar macrophages and for surfactant homeostasis. The role of GM-CSF has been proven especially in primary pulmonary alveolar proteinosis which is currently considered an auto-immune disease involving the development of GM-CSF neutralising autoantibodies. In most cases, the prognosis for the disease in adult patients is good, even though there is a 10 to 15% rate of patients who develop respiratory failure. Total pulmonary lavage is considered to be the standard method of treatment. In recent years, recombinant human GM-CSF has been studied as a prospective therapy for the treatment of pulmonary alveolar proteinosis. PMID:18072433

  18. Fatal accident caused by isoflurane abuse.

    PubMed

    Pavlic, M; Haidekker, A; Grubwieser, P; Rabl, W

    2002-12-01

    A fatal accident after isoflurane abuse is presented in this report. A hospital employee was found dead in the operating area with a plastic bag over his head. In his locker an almost empty bottle of isoflurane was found. Autopsy revealed signs of asphyxiation and toxicological examination revealed nordazepam and isoflurane in non-toxic concentrations in the blood. Quantification of the anaesthetic was also carried out in urine, gastric contents, liver, kidney and brain samples, and in addition, oxazepam, prothipendyl and metabolites of midazolam and prothipendyl were found in the urine. Although the drug problems of the deceased were known before, no efforts had been made to restrict access to these drugs. PMID:12596784

  19. Comparison of hemodynamic response to adrenaline infiltration in children undergoing cleft palate repair during general anesthesia with sevoflurane and isoflurane

    PubMed Central

    Gunnam, Poojita Reddy; Durga, Padmaja; Gurajala, Indira; Kaluvala, Prasad Rao; Veerabathula, Prardhana; Ramachandran, Gopinath

    2016-01-01

    Background and Aims: Systemic absorption of adrenaline often used for infiltration during cleft palate surgery leads to adverse hemodynamic responses. These hemodynamic responses may be attenuated by the volatile anesthetics. This study aims to compare the hemodynamic responses to adrenaline infiltration during isoflurane (ISO) and sevoflurane (SEVO) anesthesia. Material and Methods: Sixty children aged between 9 months and 48 months, weighing between 8 kg and 20 kg, undergoing primary repair of cleft palate were randomly allocated into two groups: Group ISO - anesthesia maintained with ISO (2 minimum alveolar concentrations [MAC]) and nitrous oxide 50% and group SEVO - maintained on SEVO (2 MAC) and nitrous oxide 50%. Surgical site was infiltrated with 1 ml/kg of 1:200,000 solution of adrenaline with 0.5% lignocaine. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) were noted at the end of infiltration and every 1 min for 5 min following infiltration. The percentage change of hemodynamic responses from baseline, following infiltration were compared between the two groups. Results: There was no significant change in HR from baseline, and the response was comparable between the agents at all times. The blood pressure (BP) increased from baseline in both the groups but the increase was greater in SEVO than ISO group at 2 and 3 min after infiltration. The maximum change in HR from baseline (group ISO median 10.9% [interquartile range (IQR) 4.5-23.0] vs. group SEVO 26.5% [11.9-44.6]) was comparable in both the groups (P = 0.169). The maximum change in SBP was significantly greater in group SEVO than group ISO (42.8% [IQR 20.0-60.9] vs. 26.0 [11.3-44.5], P = 0.04). The incidence of significant change (>20%) of SBP, DBP, and MAP from baseline was significantly greater in group SEVO after infiltration and 1 min and 2 min after infiltration. There were no arrhythmias in any of the groups. Conclusion

  20. Isoflurane Selectively Inhibits Distal Mitochondrial Complex I in Caenorhabditis Elegans

    PubMed Central

    Kayser, Ernst-Bernhard; Suthammarak, Wichit; Morgan, Phil G.; Sedensky, Margaret M.

    2011-01-01

    BACKGROUND Complex I of the electron transport chain (ETC) is a possible target of volatile anesthetics (VAs). Complex I enzymatic activities are inhibited by VAs, and dysfunction of complex I can lead to hypersensitivity to VAs in worms and in people. Mutant analysis in Caenorhabditis (C.) elegans suggests that VAs may specifically interfere with complex I function at the binding site for its substrate ubiquinone. We hypothesized that isoflurane inhibits electron transport by competing with ubiquinone for binding to complex I. METHODS Wildtype and mutant C. elegans were used to study the effects of isoflurane on isolated mitochondria. Enzymatic activities of the ETC were assayed and dose-response curves determined using established techniques. Two-dimensional native gels of mitochondrial proteins were performed after exposure of mitochondria to isoflurane. RESULTS Complex I is the most sensitive component of the ETC to isoflurane inhibition; however the proximal portion of complex I (the flavoprotein) is relatively insensitive to isoflurane. Isoflurane and quinone do not compete for a common binding site on complex I. The absolute rate of complex I enzymatic activity in vitro does not predict immobilization of the animal by isoflurane. Isoflurane had no measurable effect on stability of mitochondrial supercomplexes. Reduction of ubiquinone by complex I displayed positive cooperative kinetics not disrupted by isoflurane. CONCLUSIONS Isoflurane directly inhibits complex I at a site distal to the flavoprotein subcomplex. However, we have excluded our original hypothesis that isoflurane and ubiquinone compete for a common hydrophobic binding site on complex I. In addition, immobilization of the nematode by isoflurane is not due to limiting absolute amounts of complex I electron transport as measured in isolated mitochondria. PMID:21467554

  1. Effect of 50% and maximal inspired oxygen concentrations on respiratory variables in isoflurane-anesthetized horses

    PubMed Central

    2011-01-01

    Background The purpose of this study was to compare the effects of 0.5 fraction of inspired oxygen (FiO2) and >0.95 FiO2 on pulmonary gas exchange, shunt fraction and oxygen delivery (DO2) in dorsally recumbent horses during inhalant anesthesia. The use of 0.5 FiO2 has the potential to reduce absorption atelectasis (compared to maximal FiO2) and augment alveolar oxygen (O2) tensions (compared to ambient air) thereby improving gas exchange and DO2. Our hypothesis was that 0.5 FiO2 would reduce ventilation-perfusion mismatching and increase the fraction of pulmonary blood flow that is oxygenated, thus improving arterial oxygen content and DO2. Results Arterial partial pressures of O2 were significantly higher than preanesthetic levels at all times during anesthesia in the >0.95 FiO2 group. Arterial partial pressures of O2 did not change from preanesthetic levels in the 0.5 FiO2 group but were significantly lower than in the >0.95 FiO2 group from 15 to 90 min of anesthesia. Alveolar to arterial O2 tension difference was increased significantly in both groups during anesthesia compared to preanesthetic values. The alveolar to arterial O2 tension difference was significantly higher at all times in the >0.95 FiO2 group compared to the 0.5 FiO2 group. Oxygen delivery did not change from preanesthetic values in either group during anesthesia but was significantly lower than preanesthetic values 10 min after anesthesia in the 0.5 FiO2 group. Shunt fraction increased in both groups during anesthesia attaining statistical significance at varying times. Shunt fraction was significantly increased in both groups 10 min after anesthesia but was not different between groups. Alveolar dead space ventilation increased after 3 hr of anesthesia in both groups. Conclusions Reducing FiO2 did not change alveolar dead space ventilation or shunt fraction in dorsally recumbent, mechanically ventilated horses during 3 hr of isoflurane anesthesia. Reducing FiO2 in dorsally recumbent

  2. Isoflurane Preconditioning Confers Cardioprotection by Activation of ALDH2

    PubMed Central

    Lang, Xiao-E; Wang, Xiong; Zhang, Ke-Rang; Lv, Ji-Yuan; Jin, Jian-Hua; Li, Qing-Shan

    2013-01-01

    The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury. PMID:23468836

  3. Dopamine uptake dynamics are preserved under isoflurane anesthesia.

    PubMed

    Brodnik, Zachary D; España, Rodrigo A

    2015-10-01

    Fast scan cyclic voltammetry is commonly used for measuring the kinetics of dopamine release and uptake. For experiments using an anesthetized preparation, urethane is preferentially used because it does not alter dopamine uptake kinetics compared to freely moving animals. Unfortunately, urethane is highly toxic, can induce premature death during experiments, and cannot be used for recovery surgeries. Isoflurane is an alternative anesthetic that is less toxic than urethane, produces a stable level of anesthesia over extended periods, and is often used for recovery surgeries. Despite these benefits, the effects of isoflurane on dopamine release and uptake have not been directly characterized. In the present studies, we assessed the utility of isoflurane for voltammetry experiments by testing dopamine signaling parameters under baseline conditions, after treatment with the dopamine uptake inhibitor cocaine, and after exposure to increasing concentrations of isoflurane. Our results indicate that surgical levels of isoflurane do not significantly alter terminal mechanisms of dopamine release and uptake over prolonged periods of time. Consequently, we propose that isoflurane is an acceptable anesthetic for voltammetry experiments, which in turn permits the design of studies in which dopamine signaling is examined under anesthesia prior to recovery and subsequent experimentation in the same animals. PMID:26321152

  4. Evaluation of Isoflurane Overdose for Euthanasia of Neonatal Mice.

    PubMed

    Seymour, Travis L; Nagamine, Claude M

    2016-01-01

    Neonatal mice (that is, pups younger than 6 d) must be exposed to CO2 for as long as 50 min to achieve euthanasia. Alternatively, other inhalant anesthetic agents have been used to euthanize laboratory rodent species. We investigated the efficacy of isoflurane at saturated vapor pressure to euthanize neonatal mice. Neonatal mice (n = 76; age, 1 or 2 d) were exposed to isoflurane in a sealed, quart-size (0.95-L) plastic bag at room temperature. Righting and withdrawal reflexes were absent in less than 2 min. After 30 min of exposure to isoflurane, pups were removed and monitored for recovery. All pups were cyanotic and showed no detectable signs of life when they were removed from the bag. However, after 30 to 120 min after removal from the bag, 24% of isoflurane-overexposed pups began gasping and then resumed normal respiration and regained a normal pink coloration. These results demonstrate that isoflurane overexposure at saturated vapor pressure for 30 min is insufficient to euthanize neonatal mice and that isoflurane overexposure must be followed by a secondary means of euthanasia. PMID:27177567

  5. [Emergence times, hemodynamics and adverse effects of sevoflurane and isoflurane: an open, randomized, comparative phase iii study].

    PubMed

    Wiesner, G; Schwürzer, S; Hörauf, K; Hobbhahn, J

    1994-09-01

    blood pressure (Figs. 2 and 3). No adverse effects with a "probable" or "highly probable" relationship to the inhaled anaesthetic were observed. Table 4 shows the adverse events with a possible relationship to the drug administered. Further evaluations of nausea, vomiting, and dizziness are shown in Table 5. DISCUSSION. Emergence time after inhalation anaesthesia depends on pulmonary elimination and MACawake, that is, the end-tidal concentration that would allow opening of the eyes on verbal command. Pulmonary elimination depends on dose applied (MAC h), alveolar ventilation, and blood-gas solubility coefficient. Due to the lower blood-gas solubility coefficient (0.6-0.7 for sevoflurane vs. 1.3-1.4 for isoflurane) and in accordance with the investigations of Frink et al. [4] and Smith et al. [16], emergence time was significantly shorter with sevoflurane. Gender, the only difference between the two patient groups, does not influence pulmonary elimination and MACawake [8]. Supplementing inhalation anaesthesia with fentanyl, there was no difference in the time courses of heart rate and mean arterial blood pressure between sevoflurane and isoflurane. Adverse events with a possible relationship to the inhaled anaesthetic occurred in both groups. PMID:7978185

  6. Isoflurane inhibits embryonic stem cell self-renewal through retinoic acid receptor.

    PubMed

    Liu, Sheng; Zhang, Lei; Liu, Yi; Shen, Xia; Yang, Longqiu

    2015-08-01

    The commonly used inhalation anesthetic isoflurane could permeate rapidly through the placental barrier and induce toxicity to the central nervous system of the developing fetus. However, the effects of isoflurane in utero during early gestation are unknown. We therefore treated pregnant mice with 1.4% isoflurane for 2h per day for three days at day3.5 (E3.5) to day6.5 (E6.5) to investigated the toxicity of isoflurane. Pregnant mice were executed and the fetal mice were weighed and observed. Mouse ESCs (E14) was exposed to 2% isoflurane for 6h. Twenty-four hours later, self-renewal was examined with AP staining. Effects of isoflurane on the expression of RAR-γ were examined using Western blot. As a result, anesthesia with 1.4% isoflurane for 2 hour per day for 3 days reduced fetal growth and development. Isoflurane decreased self-renewal and the expression stemness genes (Nanog, Oct4, Sox2, and Lin28) in mESCs. Vitamin A attenuated the effects of isoflurane inducing self-renewal inhibition. In summary, Anesthesia with 1.4% isoflurane for 2h per day for 3 days reduced fetal growth and development. Moreover, isoflurane inhibits mESCs self-renewal through retinoic acid receptor. PMID:26349971

  7. Influence of Isoflurane on Immediate-Early Gene Expression

    PubMed Central

    Bunting, Kristopher M.; Nalloor, Rebecca I.; Vazdarjanova, Almira

    2016-01-01

    Background: Anterograde amnesia is a hallmark effect of volatile anesthetics. Isoflurane is known to affect both the translation and transcription of plasticity-associated genes required for normal memory formation in many brain regions. What is not known is whether isoflurane anesthesia prevents the initiation of transcription or whether it halts transcription already in progress. We tested the hypothesis that general anesthesia with isoflurane prevents learning-induced initiation of transcription of several memory-associated immediate-early genes (IEGs) correlated with amnesia; we also assessed whether it stops transcription initiated prior to anesthetic administration. Methods: Using a Tone Fear Conditioning paradigm, rats were trained to associate a tone with foot-shock. Animals received either no anesthesia, anesthesia immediately after training, or anesthesia before, during, and after training. Animals were either sacrificed after training or tested 24 h later for long-term memory. Using Cellular Compartment Analysis of Temporal Activity by Fluorescence in situ Hybridization (catFISH), we examined the percentage of neurons expressing the IEGs Arc/Arg3.1 and Zif268/Egr1/Ngfi-A/Krox-24 in the dorsal hippocampus, primary somatosensory cortex, and primary auditory cortex. Results: On a cellular level, isoflurane administered at high doses (general anesthesia) prevented initiation of transcription, but did not stop transcription of Arc and Zif268 mRNA initiated prior to anesthesia. On a behavioral level, the same level of isoflurane anesthesia produced anterograde amnesia for fear conditioning when administered before and during training, but did not produce retrograde amnesia when administered immediately after training. Conclusion: General anesthesia with isoflurane prevents initiation of learning-related transcription but does not stop ongoing transcription of two plasticity-related IEGs, Arc and Zif268, a pattern of disruption that parallels the effects of

  8. [Effect of the inhalation ++ anesthetic isoflurane on heart electrophysiology].

    PubMed

    Sarrión Auñón, J; Chorro Gascó, F J; Negueruela Cardo, A; Burguera Pérez, M; Sanchis Forés, J; Chuliá Campos, V; Palanca Sanfrancisco, J M; Such Belenguer, L; López Merino, V

    1992-01-01

    In two groups, A and B, both composed of 10 mongrel dogs, we studied the cardiac electrophysiologic effects of 1 and 1.5 MAC isoflurane administered by liquid injection in a closed circuit. In group B the study was done under pharmacological autonomic blockade (AB). With electrode catheters for programmed pacing and endocavitary potential recordings, we determined during the anesthesia with 1 and 1.5 MAC isoflurane: RR, spontaneous and paced AH, and HV intervals, corrected sinus recovery time (CSRT), Wenckebach point (WP), functional and effective refractory periods of atria (AFRP, AERP) and AV node (AVNFRP, AVNERP), and ventricular effective refractory period (VERP), these were compared to the ones obtained with a previous thiopental control. In group A, 1 MAC isoflurane increased over control: AERP and AH interval (p < 0.05), AFRP (p < 0.005), RR and AH paced intervals, WP, AVNFRP and VERP (p < 0.001), adding to these CSRT (p < 0.01) in 1.5 CAM. This level did not show differences with 1 MAC. In group B, 1 MAC isoflurane increased over control: AH (p < 0.05), RR, paced AH intervals, WP and AVNFRP (p < 0.001), adding to these AFRP and AERP (p < 0.05) in 1.5 MAC. This level increased with regard to 1 MAC: AFRP, AERP, AH paced interval and AVNERP (p < 0.05), and AVNFRP (p < 0.005). Isoflurane alone or with AB increased parameters of sinusal automaticity, atrial refractoriness, AV nodal conduction and refractoriness, increasing only without AB ventricular refractoriness and CSRT. With AB atrial and AV nodal refractoriness increased in an anesthetic depth dependent way. PMID:1439071

  9. Postanesthetic Effects of Isoflurane on Behavioral Phenotypes of Adult Male C57BL/6J Mice

    PubMed Central

    Asakura, Ayako; Kobayashi, Ayako; Takase, Kenkichi; Goto, Takahisa

    2015-01-01

    Isoflurane was previously the major clinical anesthetic agent but is now mainly used for veterinary anesthesia. Studies have reported widespread sites of action of isoflurane, suggesting a wide array of side effects besides sedation. In the present study, we phenotyped isoflurane-treated mice to investigate the postanesthetic behavioral effects of isoflurane. We applied comprehensive behavioral test batteries comprising sensory test battery, motor test battery, anxiety test battery, depression test battery, sociability test battery, attention test battery, and learning test battery, which were started 7 days after anesthesia with 1.8% isoflurane. In addition to the control group, we included a yoked control group that was exposed to the same stress of handling as the isoflurane-treated animals before being anesthetized. Our comprehensive behavioral test batteries revealed impaired latent inhibition in the isoflurane-treated group, but the concentration of residual isoflurane in the brain was presumably negligible. The yoked control group and isoflurane-treated group exhibited higher anxiety in the elevated plus-maze test and impaired learning function in the cued fear conditioning test. No influences were observed in sensory functions, motor functions, antidepressant behaviors, and social behaviors. A number of papers have reported an effect of isoflurane on animal behaviors, but no systematic investigation has been performed. To the best of our knowledge, this study is the first to systematically investigate the general health, neurological reflexes, sensory functions, motor functions, and higher behavioral functions of mice exposed to isoflurane as adults. Our results suggest that the postanesthetic effect of isoflurane causes attention deficit in mice. Therefore, isoflurane must be used with great care in the clinical setting and veterinary anesthesia. PMID:25806517

  10. Pulmonary alveolar proteinosis.

    PubMed

    Borie, R; Danel, C; Debray, M-P; Taille, C; Dombret, M-C; Aubier, M; Epaud, R; Crestani, B

    2011-06-01

    Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic "crazy paving" pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement. PMID:21632797

  11. Mutations M287L and Q266I in the Glycine Receptor α1 Subunit Change Sensitivity to Volatile Anesthetics in Oocytes and Neurons, but Not the Minimal Alveolar Concentration in Knockin Mice

    PubMed Central

    Borghese, Cecilia M.; Xiong, Wei; Oh, S. Irene; Ho, Angel; Mihic, S. John; Zhang, Li; Lovinger, David M.; Homanics, Gregg E.; Eger, Edmond I; Harris, R. Adron

    2012-01-01

    Background Volatile anesthetics (VAs) alter the function of key central nervous system proteins but it is not clear which, if any, of these targets mediates the immobility produced by VAs in the face of noxious stimulation. A leading candidate is the glycine receptor, a ligand-gated ion channel important for spinal physiology. VAs variously enhance such function, and blockade of spinal GlyRs with strychnine affects the minimal alveolar concentration (an anesthetic EC50) in proportion to the degree of enhancement. Methods We produced single amino acid mutations into the glycine receptorα1 subunit that increased (M287L, third transmembrane region) or decreased (Q266I, second transmembrane region) sensitivity to isoflurane in recombinant receptors, and introduced such receptors into mice. The resulting knockin mice presented impaired glycinergic transmission, but heterozygous animals survived to adulthood, and we determined the effect of isoflurane on glycine-evoked responses of brain stem neurons from the knockin mice, and the minimal alveolar concentration for isoflurane and other VAs in the immature and mature knockin mice. Results Studies of glycine-evoked currents in brain stem neurons from knock-in mice confirmed the changes seen with recombinant receptors. No increases in the minimal alveolar concentration were found in knockin mice, but the minimal alveolar concentration for isoflurane and enflurane (but not halothane) decreased in 2-week-old Q266I mice. This change is opposite to the one expected for a mutation that decreases the sensitivity to volatile anesthetics. Conclusion Taken together, these results indicate that glycine receptors containing the α1 subunit are not likely to be crucial for the action of isoflurane and other VAs. PMID:22885675

  12. Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.

    PubMed

    Sosunov, Sergey A; Ameer, Xavier; Niatsetskaya, Zoya V; Utkina-Sosunova, Irina; Ratner, Veniamin I; Ten, Vadim S

    2015-01-01

    This study demonstrates that in mice subjected to hypoxia-ischemia (HI) brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF) and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on recovery of

  13. [Pulmonary alveolar proteinosis].

    PubMed

    Floarea-Strat, Alina; Stanciu, Adriana; Creţeanu, Mihai

    2003-01-01

    It is a disease of obscure cause that is characterized by the accumulation of a granular material that contains abundant lipid within the alveoli of lung. Pulmonary alveolar proteinosis (PAP) has been divided into a congenital and an adult form. The acquired form has been subdivided into a idiopathic form and a secondary form associated with a know disorder or exposure as silica, aluminium, titanium. Dyspnea and cough are the most common presenting symptoms. Chest pain, hemoptysis, fever and weight loss are variably reported. Pathogenesis remains unknown, but evidence points to a dysfunction of alveolar macrophages. Mice genetically deficient in granulocyte macrophagecolony stimulating factor (GM-CSF) show an alveolar proteinosis. A neutralizing antibody against GM-CSF was found in bronchoalveolar lavage fluid and serum of patients with idiopathic PAP. Currently, no specific therapy exists for pulmonary alveolar proteinosis, and sequential whole lung lavage is standard treatment. PMID:14756054

  14. Isoflurane Prevents Acute Lung Injury Through ADP-Mediated Platelet Inhibition

    PubMed Central

    Harr, Jeffrey N.; Moore, Ernest E.; Stringham, John; Wohlauer, Max V.; Fragoso, Miguel; Jones, Wilbert L.; Gamboni, Fabia; Silliman, Christopher C.; Banerjee, Anirban

    2012-01-01

    Background Growing evidence suggests platelets are essential in post-traumatic acute lung injury (ALI). Halogenated ethers interfere with platelet-granulocyte aggregate formation. The potential benefit of halogenated ethers has not been investigated in trauma/hemorrhagic shock (T/HS) models. Therefore, we hypothesized that isoflurane decreases T/HS-mediated ALI through platelet inhibition. Methods Sprauge-Dawley rats (n=47) were anesthetized by either pentobarbital or inhaled isoflurane, and placed into groups: control, trauma (laparotomy) sham shock, T/HS (MAP of 30 mmHg × 45 min), pre-treatment with an ADP receptor antagonist, or T/HS with isoflurane initiated during resuscitation. ALI was determined by BALF protein and pulmonary immunofluorescence. PlateletMapping™ specifically evaluated thrombin-independent inhibition of the ADP and AA pathways of platelet activation. Results Pre-treatment with isoflurane abrogated ALI as measured by both BAL fluid protein and pulmonary immunofluorescence (p<0.001). PlateletMapping™, revealed specific platelet ADP-pathway inhibition with isoflurane (p<0.001). Pre-treatment with an ADP receptor antagonist decreased ALI to sham levels, confirming that specific platelet ADP inhibition decreases ALI. Isoflurane initiated during resuscitation also decreased ALI (p<0.001). Conclusion Isoflurane attenuates ALI through an anti-platelet mechanism, in part, through inhibition of the platelet ADP pathway. Isoflurane given post-injury also protects against ALI, and highlights the potential applications of this therapy in various ischemia/reperfusion clinical scenarios. PMID:22828148

  15. Tolerance to Isoflurane Does Not Occur in Developing Xenopus laevis Tadpoles

    PubMed Central

    Milutinovic, Pavle S.; Zhao, Jing

    2009-01-01

    Introduction Tolerance is observed for a variety of central nervous system depressants including ethanol, which is an anesthetic, but has not been convincingly demonstrated for a potent halogenated volatile anesthetic. Failure to demonstrate tolerance to these agents may be the result of inadequate exposure to anesthetic. In this study, we exposed Xenopus laevis tadpoles to surgical anesthetic concentrations of isoflurane for one week. Methods Xenopus laevis tadpoles were produced by in vitro fertilization, and exposed to isoflurane (0.59%, 0.98%, 1.52%) or oxygen for one week starting from the time of fertilization. Results Changes in anesthetic EC50 were small and not in a consistent direction. Control animals had an anesthetic EC50 of 0.594% ± 0.003% isoflurane. Tadpoles exposed to 1.52% isoflurane had a lower EC50 than controls (by 16%), while tadpoles raised under 0.59 and 0.98% isoflurane had higher EC50s than control (by 4.7% and 7.4%, respectively). Conclusion We provide the first description of week-long exposures of vertebrates to surgical anesthetic concentrations of isoflurane, and the first report of such exposures in developing vertebrates. Tolerance to isoflurane does not occur in developing Xenopus laevis tadpoles. Taken together with studies in other organisms, the development of tolerance to ethanol but not isoflurane suggests that mechanisms these drugs share probably do not account for the development of tolerance. PMID:19095846

  16. Analgesic effects of maxillary and inferior alveolar nerve blocks in cats undergoing dental extractions.

    PubMed

    Aguiar, Joana; Chebroux, Alexandre; Martinez-Taboada, Fernando; Leece, Elizabeth A

    2015-02-01

    The aim of this study was to evaluate the analgesic effects of maxillary and/or inferior alveolar nerve blocks with lidocaine and bupivacaine in cats undergoing dental extractions. Twenty-nine cats were enrolled. Using an adapted composite pain scale, cats were pain scored before the dental procedure and 30 mins, and 1, 2 and 4 h after isoflurane disconnection. Cats were sedated with buprenorphine (20 µg/kg), medetomidine (10 µg/kg) and acepromazine (20 µg/kg) intramuscularly. Anaesthesia was induced using alfaxalone (1-2 mg/kg) intravenously and maintained with isoflurane in oxygen. Each cat was randomly assigned to receive maxillary and/or inferior alveolar nerve blocks or no nerve blocks prior to dental extractions. Each nerve block was performed using lidocaine (0.25 mg/kg) and bupivacaine (0.25 mg/kg). Heart rate, systolic arterial blood pressure, respiratory rate, end tidal carbon dioxide and isoflurane vaporiser settings were recorded 5 mins before and after the dental extractions, and the difference calculated. Group mean differences (mean ± SD) for heart rate (-9.7 ± 10.6 vs 7.6 ± 9.5 beats/min [nerve block vs control group, respectively], P <0.0001), systolic arterial blood pressure (-10.33 ± 18.44 vs 5.21 ± 15.23 mmHg, P = 0.02) and vaporiser settings (-0.2 ± 0.2 vs 0.1 ± 0.4, P = 0.023) were significantly different between groups. The control group had higher postoperative pain scores (median [interquartile range]) at 2 h (3 [1.75-4.00] vs 1 [0-2], P = 0.008) and 4 h (4 [2-6] vs 2 [1-2], P = 0.006) after the dental extractions. Maxillary and inferior alveolar nerve blocks with lidocaine and bupivacaine administered prior to dental extractions resulted in a reduction in heart rate and blood pressure while allowing for a reduction in isoflurane. Cats receiving nerve blocks had lower postoperative pain scores than the group without nerve blocks. PMID:24820999

  17. Pulmonary alveolar proteinosis.

    PubMed

    Khan, Ajmal; Agarwal, Ritesh

    2011-07-01

    Pulmonary alveolar proteinosis is a rare but potentially treatable disease, characterized by impaired surfactant metabolism that leads to accumulation in the alveoli of proteinaceous material rich in surfactant protein and its component. Novel insights from an animal model aided the discovery of granulocyte macrophage colony stimulating factor (GM-CSF) antibodies as a pathogenetic mechanism in human pulmonary alveolar proteinosis. The vast majority of pulmonary alveolar proteinosis occurs as an autoimmune disease; less commonly, it is congenital or secondary to an underlying disorder such as infection, hematological malignancy, or immunodeficiency. The subacute indolent course of this disease often delays the diagnosis by months to years. Crazy-paving appearance in a geographic distribution is a characteristic feature of this disease visible on high-resolution computed tomography (CT). A definitive diagnosis, however, requires lung biopsy, which typically shows partial or complete filling of alveoli with periodic-acid-Schiff-positive granular and eosinophilic material in preserved alveolar architecture. Patients with minimal symptoms are managed conservatively, whereas patients with hypoxemia require a more aggressive approach. Whole-lung lavage is the most widely accepted therapy for symptomatic pulmonary alveolar proteinosis. Correction of GM-CSF deficiency with exogenous GM-CSF is an alternative therapy. The combination of a systemic treatment (GM-CSF) and a local treatment (whole-lung lavage) augmenting the action of one another is a promising new approach. As the knowledge about this rare disease increases, the role of novel therapies is likely to be better defined and optimized. PMID:21496372

  18. Pulmonary alveolar proteinosis.

    PubMed

    Patel, Sandeep M; Sekiguchi, Hiroshi; Reynolds, Jordan P; Krowka, Michael J

    2012-01-01

    Pulmonary alveolar proteinosis (PAP) is a disease of alveolar accumulation of phospholipoproteinaceous material that results in gas exchange impairment leading to dyspnea and alveolar infiltrates. There are three forms of PAP: congenital, acquired and idiopathic; of which the latter two are predominant in the adult population. Previous case studies have found that the acquired form can be secondary to various autoimmune, infectious, malignant and environmental etiologies. Recent advances in the understanding of the pathophysiology of PAP demonstrate that the idiopathic form is due to antigranulocyte macrophage-colony stimulating factor antibodies. Therapeutic targets that replace granulocyte macrophage colony stimulating factor or remove these antibodies are being actively developed. The current standard of care is to perform whole lung lavage on these patients to clear the alveolar space to help improve respiratory physiology. A case of PAP is reported, followed by a literature review on the diagnosis and management of this rare condition with the aim of increasing awareness among physicians when treating patients who present with alveolar infiltrates. PMID:22891182

  19. ANESTHETIC INDUCTION AND RECOVERY PARAMETERS IN BEARDED DRAGONS (POGONA VITTICEPS): COMPARISON OF ISOFLURANE DELIVERED IN 100% OXYGEN VERSUS 21% OXYGEN.

    PubMed

    O, Odette; Churgin, Sarah M; Sladky, Kurt K; Smith, Lesley J

    2015-09-01

    Inland bearded dragons (Pogona vitticeps, n=6) were anesthetized for 1 hr using isoflurane in either 100% oxygen or 21% oxygen (FI 21; medical-grade room air). Parameters of anesthetic depth were recorded throughout both induction and recovery by an observer blinded to the fraction of inspired oxygen (FiO2), including the loss and return of withdrawal and righting reflexes, muscle tone, ability to intubate or extubate, and return to spontaneous respiration. Physiologic data were recorded every 5 min throughout the anesthetic procedures, including heart rate, body temperature, end-tidal CO2, hemoglobin oxygen saturation (SpO2), and percent expired isoflurane. Lizards were subjected to application of a noxious stimulus (needle stick) at 0, 30, and 60 min, and responses recorded. Following a minimum 7-day washout period, the experiment was repeated with each lizard subjected to the other protocol in a randomized, complete crossover design. The only statistically significant difference was a lower mean SpO2 in the group inspiring 21% oxygen (P<0.0020). No statistically significant differences were detected in any parameters during induction or recovery; however, all values were uniformly shorter for the FI 21 group, indicating a possible clinically significant difference. A larger sample size may have detected statistically significant differences. Further studies are needed to evaluate these effects in other reptile species and with the concurrent use of injectable anesthetic and analgesic drugs. PMID:26352957

  20. Effect of high dose isoflurane on cerebral blood flow in macaque monkeys

    PubMed Central

    Li, Chun-Xia; Patel, Sudeep; Wang, Danny JJ; Zhang, Xiaodong

    2014-01-01

    The effect of high dose isoflurane on cerebral blood flow (CBF) was investigated in adult macaque monkeys receiving 1% to 2% isoflurane with the pseudo continuous arterial-spin-labeling (pCASL) MRI technique. High concentration (2%) of isoflurane resulted in significant increase in the mean CBF of the global, cortical, subcortical regions and the regional CBF in all subcortical structures and most cortical structures (such as motor cortex, anterior cingulate cortex, but not media prefrontal cortex). In addition, the changes of regional CBF in the affected regions correlated linearly with increasing isoflurane concentrations. The study demonstrates region specific CBF abnormal increase in adult macaque monkeys under high dose (2%) isoflurane and suggests the brain functionality in corresponding structures may be affected and need to be taken consideration in either human or non-human primate neuroimaging studies. PMID:24890304

  1. Pulmonary alveolar microlithiasis

    PubMed Central

    Kashyap, Surender; Mohapatra, Prasanta R.

    2013-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare, chronic lung disease with bilateral intra-alveolar calcium and phosphate deposition throughout the lung parenchyma with predominance to lower and midzone. Although, etiology and pathogenesis of PAM is not fully understood, the mutation in SLC34A2 gene that encodes a sodium-phosphate co-transporter in alveolar type II cells resulting in the accumulation and forming of microliths rich in calcium phosphate (due to impaired clearance) are considered to be the cause of the disease. Chest radiograph and high-resolution CT of thorax are nearly pathognomonic for diagnosing PAM. HRCT demonstrates diffuse micronodules showing slight perilobular predominance resulting in calcification of interlobular septa. Patients with PAM are asymptomatic till development of hypoxemia and cor-pulmonale. No therapy has been proven to be beneficial except lung transplantation. PMID:23741096

  2. Alveolar wall relations.

    PubMed

    Gil, J

    1982-01-01

    We have presented a highly dynamic view of the alveolar septum and its main enclosed structure, the dense capillary network. The septal or perimicrovascular interstitium is the space between alveolar epithelial sheets after exclusion of the capillary network. It contains cells, fibers, and a viscous matrix. Capillaries form a very complex network, which closely follows the geometry of the terminal airways and participates in functional adaptations of the wall, particularly septal pleating. The level of filling and configuration of different capillaries ranging from collapse to full distension are variable, depending on factors such as transmural balance of forces but also on tissular configuration. Alveolar flooding of any cause will produce an immediate change of capillary configuration and volume. PMID:6953828

  3. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia

    PubMed Central

    Taylor, Norman E.; Chemali, Jessica J.; Brown, Emery N.; Solt, Ken

    2012-01-01

    BACKGROUND A recent study showed that methylphenidate induces emergence from isoflurane anesthesia. Methylphenidate inhibits dopamine and norepinephrine reuptake transporters. The objective of this study was to test the hypothesis that selective dopamine receptor activation induces emergence from isoflurane anesthesia. METHODS In adult rats, we tested the effects of chloro-APB (D1 agonist) and quinpirole (D2 agonist) on time to emergence from isoflurane general anesthesia. We then performed a dose–response study to test for chloro-APB-induced restoration of righting during continuous isoflurane anesthesia. SCH-23390 (D1 antagonist) was used to confirm that the effects induced by chloro-APB are specifically mediated by D1 receptors. In a separate group of animals, spectral analysis was performed on surface electroencephalogram recordings to assess neurophysiological changes induced by chloro-APB and quinpirole during isoflurane general anesthesia. RESULTS Chloro-APB decreased median time to emergence from 330s to 50s. The median difference in time to emergence between the saline control group (n=6) and the chloro-APB group (n = 6) was 222s (95% CI: 77–534s, Mann-Whitney test). This difference was statistically significant (p = 0.0082). During continuous isoflurane anesthesia, chloro-APB dose-dependently restored righting (n = 6) and decreased electroencephalogram delta power (n = 4). These effects were inhibited by pretreatment with SCH-23390. Quinpirole did not restore righting (n = 6) and had no significant effect on the electroencephalogram (n = 4) during continuous isoflurane anesthesia. CONCLUSIONS Activation of D1 receptors by chloro-APB decreases time to emergence from isoflurane anesthesia, and produces behavioral and neurophysiological evidence of arousal during continuous isoflurane anesthesia. These findings suggest that selective activation of a D1 receptor-mediated arousal mechanism is sufficient to induce emergence from isoflurane general

  4. Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling

    SciTech Connect

    Ni, Cheng; Li, Zhengqian; Qian, Min; Zhou, Yang; Wang, Jun; Guo, Xiangyang

    2015-05-15

    Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased and peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporine A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.

  5. Isoflurane-Induced Spatial Memory Impairment in Mice is Prevented by the Acetylcholinesterase Inhibitor Donepezil

    PubMed Central

    Wang, Beilei; Xu, Huan; Li, Wen; Chen, Jie; Wang, Xiangrui

    2011-01-01

    Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane. PMID:22114680

  6. Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil.

    PubMed

    Su, Diansan; Zhao, Yanxing; Wang, Beilei; Xu, Huan; Li, Wen; Chen, Jie; Wang, Xiangrui

    2011-01-01

    Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane. PMID:22114680

  7. Isoflurane attenuates LPS-induced acute lung injury by targeting miR-155-HIF1-alpha.

    PubMed

    Hu, Rong; Zhang, Ying; Yang, Xiaohua; Yan, Jia; Sun, Yu; Chen, Zhifeng; Jiang, Hong

    2015-01-01

    Isoflurane alleviates the inflammatory response in endotoxin-induced acute lung injury (ALI). In this study, we investigated the protective mechanism of isoflurane postconditioning in lipopolysaccharide (LPS)induced ALI. Exposure to isoflurane decreased miR-155 and upregulated HIF-1 alpha and HO-1 mRNA and protein. The effects of isoflurane on HIF-1 alpha mRNA and protein could be inhibited by overexpression of miR-155. Furthermore, mice overexpressing miR-155 had higher levels of TNF-alpha and IL-1 beta in BALF when exposed to isoflurane after LPS challenge.Conversely, downregulation of miR-155 promoted isoflurane effects on HIF-1 alpha expression. These results suggest that isoflurane posttreatment hr alleviates LPS-induced ALI and cell injury by triggering miR-155-HIF-1 alpha pathway, leading to upregulation of HO-1. PMID:25553444

  8. Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats

    PubMed Central

    Yang, Chun; Zhu, Bin; Ding, Jie; Wang, Zhi-Gang

    2014-01-01

    Several lines of evidence demonstrate that isoflurane anesthesia would be a great risk factor for the patients undergoing surgeries to suffer from postoperative cognitive dysfunction (POCD). Additionally, diabetes is also an important pathogenic factor for the emergence of cognitive dysfunction. If patient is suffering from diabetes, the incidence of cognitive dysfunction greatly increased. We therefore aimed to investigate the effects of isoflurane anesthesia on cognitive dysfunction in a diabetic rat model induced by a single injection of streptozotocin (STZ). Wistar rats received 2 h of 2% isoflurane or oxygen exposure 1 month after a single intraperitoneal injection of 60 mg/kg of STZ or the vehicle. The results showed that isoflurane anesthesia significantly aggravates STZ-induced an increase of the latency to the platform and a decrease of the proportion of time spent in the target quadrant of rats in Morris water maze test. In addition to the expression of amyloid-β (Aβ), superoxide dismutase (SOD), malonyldialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), isoflurane anesthesia significantly increased as compared with a single injection of STZ. However, isoflurane anesthesia had no effect on the blood glucose and leptin. In conclusion, our results suggested that isoflurane anesthesia aggravating cognitive impairment induced by STZ is probably related to the activation of oxidative stress and inflammatory response in rat hippocampus. PMID:24955160

  9. Increased extrasynaptic GluN2B expression is involved in cognitive impairment after isoflurane anesthesia

    PubMed Central

    LI, LUNXU; LI, ZHENGQIAN; CAO, YIYUN; FAN, DONGSHENG; CHUI, DEHUA; GUO, XIANGYANG

    2016-01-01

    There is increasing concern regarding the postoperative cognitive dysfunction (POCD) in the aging population, and general anesthetics are believed to be involved. Isoflurane exposure induced increased N-methyl-D-aspartic acid receptor (NMDAR) GluN2B subunit expression following anesthesia, which was accompanied by alteration of the cognitive function. However, whether isoflurane affects this expression in different subcellular compartments, and is involved in the development of POCD remains to be elucidated. The aims of the study were to investigate the effects of isoflurane on the expression of the synaptic and extrasynaptic NMDAR subunits, GluN2A and GluN2B, as well as the associated alteration of cognitive function in aged rats. The GluN2B antagonist, Ro25–6981, was given to rats exposed to isoflurane to determine the role of GluN2B in the isoflurane-induced alteration of cognitive function. The results showed that spatial learning and memory tested in the Morris water maze (MWM) was impaired at least 7 days after isoflurane exposure, and was returned to control levels 30 days thereafter. Ro25-6981 treatment can alleviate this impairment. Extrasynaptic GluN2B protein expression, but not synaptic GluN2B or GluN2A, increased significantly after isoflurane exposure compared to non-isoflurane exposure, and returned to control levels approximately 30 days thereafter. The results of the present study indicated that isoflurane induced the prolonged upregulation of extrasynaptic GluN2B expression after anesthesia and is involved in reversible cognitive impairment. PMID:27347033

  10. Isoflurane post-treatment improves pulmonary vascular permeability via upregulation of heme oxygenase-1.

    PubMed

    Dong, Xiang; Hu, Rong; Sun, Yu; Li, Qifang; Jiang, Hong

    2013-09-01

    Isoflurane (ISO) has been shown to attenuate acute lung injury (ALI). Induction of heme oxygenase-1 (HO-1) and suppression of inducible nitric oxide synthase (iNOS) expression provide cytoprotection in lung and vascular injury. The aim of this study was to investigate the effect of post-treatment with isoflurane on lung vascular permeability and the role of HO-1 in an ALI rat model induced by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly assigned to one of four groups: sham group, sham rats post-treated with vehicle (Sham); CLP group, CLP rats post-treated with vehicle (CLP); ISO group, CLP rats post-treated with isoflurane (ISO); and ZnPP group, CLP rats injected with zinc protoporphyrin IX (ZnPP), a competitive inhibitor of HO-1, 1 hour before the operation, and post-treated with isoflurane (ZnPP). Isoflurane (1.4%) was administered 2 hour after CLP. At 24 hour after CLP, the extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye (EBD) extravasation, lung permeability index (LPI), as well as histological and immunohistochemical examinations. We also determined pulmonary iNOS and HO-1 expression. Compared with the CLP group, the isoflurane post-treatment group showed improved pulmonary microvascular permeability as detected by EBD extravasation, LPI, as well as histological and immunohistochemical examinations. Furthermore, isoflurane decreased iNOS and increased HO-1 expression in lung tissue. Pretreatment with ZnPP prevented the protective effects of isoflurane in rats. These findings indicate that the protective role of isoflurane post-conditioning against CLP-induced lung injury may be associated with its role in upregulating HO-1 in ALI. PMID:23919323

  11. Vitamin C Attenuates Isoflurane-Induced Caspase-3 Activation and Cognitive Impairment.

    PubMed

    Cheng, Baiqi; Zhang, Yiying; Wang, Arthur; Dong, Yuanlin; Xie, Zhongcong

    2015-12-01

    Anesthetic isoflurane has been reported to induce caspase-3 activation. The underlying mechanism(s) and targeted intervention(s), however, remain largely to be determined. Vitamin C (VitC) inhibits oxidative stress and apoptosis. We therefore employed VitC to further determine the up-stream mechanisms and the down-stream consequences of the isoflurane-induced caspase-3 activation. H4 human neuroglioma cells overexpressed human amyloid precursor protein (H4-APP cells) and rat neuroblastoma cells were treated either with (1) 2% isoflurane or (2) with the control condition, plus saline or 400 μM VitC for 3 or 6 h. Western blot analysis and fluorescence assay were utilized at the end of the experiments to determine caspase-3 activation, levels of reactive oxygen species and ATP, and mitochondrial function. The interaction of isoflurane (1.4% for 2 h) and VitC (100 mg/kg) on cognitive function in mice was also assessed in the fear conditioning system. Here, we show for the first time that the VitC treatment attenuated the isoflurane-induced caspase-3 activation. Moreover, VitC mitigated the isoflurane-induced increases in the levels of reactive oxygen species, opening of mitochondrial permeability transition pore, reduction in mitochondrial membrane potential, and the reduction in ATP levels in the cells. Finally, VitC ameliorated the isoflurane-induced cognitive impairment in the mice. Pending confirmation from future studies, these results suggested that VitC attenuated the isoflurane-induced caspase-3 activation and cognitive impairment by inhibiting the isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. These findings would promote further research into the underlying mechanisms and targeted interventions of anesthesia neurotoxicity. PMID:25367886

  12. TNF-α receptor antagonist attenuates isoflurane-induced cognitive impairment in aged rats

    PubMed Central

    YANG, NENGLI; LIANG, YAFENG; YANG, PEI; WANG, WEIJIAN; ZHANG, XUEZHENG; WANG, JUNLU

    2016-01-01

    Postoperative cognitive dysfunction (POCD), a common clinical in aged patients, is characterized by deficits in cognitive functions in patients following anesthesia and surgery. It has been demonstrated that isoflurane may lead to cognitive impairment in aged rats; however, effective clinical interventions for preventing this disorder are limited. Tumor necrosis factor (TNF)-α has been suggested to be involved in neuroinflammation as well as the development of POCD. Accordingly, the present study aimed to investigate whether TNF-α signaling is involved in the isoflurane-induced cognitive impairment in aged rats, and whether TNF-α receptor antagonist are able to attenuate isoflurane-induced cognitive impairment in aged rats. A population of 20-month-old rats were administered TNF-α receptor antagonist R-7050 or an equal volume of saline by intraperitoneal injection 12 h prior to exposure to isoflurane to model cognitive impairment following anesthesia in old patients. Then the rats were exposed to 1.3% isoflurane for 4 h. In the control group, rats showed impaired cognitive functions evaluated by Morris water maze assay after isoflurane exposure. Furthermore, isoflurane exposure induced marked upregulation of proinflammatory cytokines, including interleukin (IL)-1β, TNF-α, IL-6 and IL-8 in the hippocampus tissue. In the experimental group, intracisternal administration of TNF-α receptor antagonist R-7050 significantly attenuated isoflurane-induced cognitive impairment and upregulation of proinflammatory cytokines. Further investigation revealed that intracisternal administration of TNF-α receptor antagonist R-7050 notably suppressed isoflurane-induced activation of NF-κB and MAPK signaling. Collectively, the present results suggest that TNF-α receptor antagonist may serve as a potential agent for the prevention of anesthesia-induced cognitive decline in aged patients. PMID:27347079

  13. Isoflurane attenuates lipopolysaccharide-induced acute lung injury by inhibiting ROS-mediated NLRP3 inflammasome activation

    PubMed Central

    Yin, Ning; Peng, Zhendan; Li, Bin; Xia, Jiangyan; Wang, Zhen; Yuan, Jing; Fang, Lei; Lu, Xinjiang

    2016-01-01

    Nucleotide-binding domains and leucine-rich repeat (NLR) pyrin domains containing 3 (NLRP3) inflammasome are highly involved in the pathogenesis of acute lung injury (ALI) wherein alveolar macrophages (AMs) play a crucial role. Isoflurane (ISO) has been shown to attenuate ALI. However, the inhibitory effects of ISO on NLRP3 activation in lipopolysaccharide (LPS)-induced ALI remain unknown. Here, we showed that 1.4% ISO post-treatment reduced LPS-induced body weight loss, pulmonary histopathological injury, edema, and vascular permeability in rats. ISO attenuated LPS-triggered inflammation, as evidenced by reductions in the number of total cells, neutrophils, and macrophages, and the release of IL-1β and IL-18 in the bronchoalveolar lavage fluid. ISO treatment decreased the myeloperoxidase activity, F4/80-positive cells, and the mRNA expression of IL-1β and IL-18 in the lung tissues of LPS-treated rats. Mechanistically, ISO reduced NLRP3 activation and caspase-1 activity in a reactive oxygen species (ROS)-dependent manner. An in vitro study that ISO inhibited LPS-induced AM activation partly confirmed in vivo findings. Overall, these results indicate that ISO post-conditioning alleviated LPS-induced ALI possibly by inhibiting ROS-mediated NLRP3 inflammasome activation. PMID:27347312

  14. Pulmonary surfactant surface tension influences alveolar capillary shape and oxygenation.

    PubMed

    Ikegami, Machiko; Weaver, Timothy E; Grant, Shawn N; Whitsett, Jeffrey A

    2009-10-01

    Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb(-/-) mice, thereby inhibiting surface tension-lowering properties of surfactant in vivo within 24 hours after depletion of Sftpb. Minimum surface tension of isolated surfactant was increased and oxygen saturation was significantly reduced after 2 days of SP-B deficiency in association with deformation of alveolar capillaries. Intravascularly injected 3.2-mum-diameter microbeads through jugular vein were retained within narrowed pulmonary capillaries after reduction of SP-B. Ultrastructure studies demonstrated that the capillary protrusion typical of the normal alveolar-capillary unit was reduced in size, consistent with altered pulmonary blood flow. Pulmonary hypertension and intrapulmonary shunting are commonly associated with surfactant deficiency and dysfunction in neonates and adults with respiratory distress syndromes. Increased surfactant surface tension caused by reduction in SP-B induced narrowing of alveolar capillaries and oxygen desaturation, demonstrating an important role of surface tension-lowering properties of surfactant in the regulation of pulmonary vascular perfusion. PMID:19202005

  15. Pulmonary alveolar proteinosis.

    PubMed

    Wang, Tisha; Lazar, Catherine A; Fishbein, Michael C; Lynch, Joseph P

    2012-10-01

    Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the accumulation of surfactant lipids and protein in the alveolar spaces, with resultant impairment in gas exchange. The clinical course can be variable, ranging from spontaneous resolution to respiratory failure and death. PAP in all forms is caused by excessive accumulation of surfactant within the alveolar spaces. Autoimmune PAP accounts for the vast majority of cases in humans and is caused by autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF), which results in impaired catabolism and clearance of surfactant lipids and proteins. Inherited or congenital forms of PAP are exceptionally rare and caused by mutations of genes encoding for surfactant proteins. Secondary forms of PAP are associated with diverse clinical disorders and are caused by reduced alveolar macrophage numbers or function with resultant reduced pulmonary clearance of surfactant. PAP is characterized by progressive exertional dyspnea and nonproductive cough with hypoxemia. Bilateral infiltrates are typically present on chest radiograph, and high-resolution computed tomography reveals diffuse ground-glass opacities and airspace consolidation with interlobular septal thickening in a characteristic "crazy paving" pattern. Although surgical lung biopsy will provide a definitive diagnosis, a combination of typical clinical and imaging features with periodic acid-Schiff (PAS)-positive material on bronchoalveolar lavage and transbronchial biopsies is usually sufficient. The standard of care for treatment of PAP remains whole lung lavage, but treatment is not required in all patients. Autoimmune PAP has also been successfully treated with GM-CSF, both inhaled and systemic, but the optimal dose, duration, and route of administration of GM-CSF have not been elucidated. PMID:23001804

  16. Alveolar Development and Disease

    PubMed Central

    Weaver, Timothy E.

    2015-01-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis. PMID:25932959

  17. Alveolar development and disease.

    PubMed

    Whitsett, Jeffrey A; Weaver, Timothy E

    2015-07-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis. PMID:25932959

  18. Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys

    PubMed Central

    Winegar, Bruce D; MacIver, M Bruce

    2006-01-01

    Background Anesthetic-induced CNS depression is thought to involve reduction of glutamate release from nerve terminals. Recent studies suggest that isoflurane reduces glutamate release by block of Na channels. To further investigate this question we examined the actions of isoflurane, TTX, extracellular Ca2+, CNQX and stimulus voltage (stim) on glutamate-mediated transmission at hippocampal excitatory synapses. EPSPs were recorded from CA1 neurons in rat hippocampal brain slices in response to Schaffer-collateral fiber stimulation. Results Isoflurane (350 μM; 1 MAC) reversibly depressed EPSP amplitudes by ~60% while facilitation increased ~20%. Consistent with previous studies, these results indicate a presynaptic site of action that involves reduced excitation-release coupling. EPSPs were depressed to comparable levels by TTX (60 nM) or lowered stim, but facilitation was not changed, indicating a simple failure of axonal conduction. Similarly, partial antagonism of postsynaptic glutamate receptors with CNQX (10 μM) depressed EPSP amplitudes with no change in facilitation. However, EPSP depression by low external Ca2+ (0.8 mM) was accompanied by an increase in facilitation comparable to isoflurane. Isoflurane depression of EPSP amplitudes could also be partly reversed by high external Ca2+ (4 mM) that also decreased facilitation. Isoflurane or low Ca2+ markedly reduced the slopes of fiber volley (FV)-EPSP input-output curves, consistent with little or no effect on FVs. By contrast, TTX didn't alter the FV-EPSP curve slope, indicating that EPSP depression resulted from FV depression. FVs were remarkably resistant to isoflurane. Somatic spike currents were unaffected by 350 μM (1 MAC) isoflurane as well. The EC50 for isoflurane depression of FVs was ~2.8 mM (12 vol. %; 8 MAC). Conclusion Isoflurane appears to depress CA1 synapses at presynaptic sites downstream from Na channels, as evident by the increased facilitation that accompanies EPSP depression. Fiber

  19. Awakening arterial blood and end-tidal concentrations of isoflurane in female surgical patients.

    PubMed

    Lin, Tso-Chou; Lu, Chih-Cherng; Hsu, Che-Hao; Pergolizz, Joseph V; Chang, Cheng-Chang; Lee, Meei-Shyuan; Ho, Shung-Tai

    2016-07-01

    Delayed extubation occurs after isoflurane anesthesia, especially following prolonged surgical duration. We aimed to determine the arterial blood concentrations of isoflurane and the correlation with end-tidal concentrations for predicting emergence from general anesthesia.Thirty-four American Society of Anesthesiologists physical status class I-II gynecologic patients were included. General anesthesia was maintained with a fixed 2% inspiratory isoflurane in 6 L/minute oxygen, which was discontinued after surgery. One milliliter of arterial blood was obtained for the determination of isoflurane concentration by gas chromatography at 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuation, in addition to the time of eye opening to verbal command, defined as awakening. Inspiratory and end-tidal concentrations were simultaneously detected by an infrared analyzer.The mean awakening arterial blood concentration of isoflurane was 0.20%, which was lower than the simultaneous end-tidal concentration 0.23%. The differences between arterial and end-tidal concentrations during emergence fell into an acceptable range (±1.96 standard deviation). After receiving a mean time of 108-minute general anesthesia, the time to eye opening after discontinuing isoflurane was 18.5 minutes (range 11-30, median 18 minutes), without statistical significance with anesthesia duration (P = 0.078) and body mass index (P = 0.170).We demonstrated the awakening arterial blood concentration of isoflurane in female patients as 0.20%. With well-assisted ventilation, the end-tidal concentration could be an indicator for the arterial blood concentration to predict emergence from shorter duration of isoflurane anesthesia. PMID:27472727

  20. Effects of isoflurane and ethanol administration on c-Fos immunoreactivity in mice.

    PubMed

    Smith, M L; Li, J; Cote, D M; Ryabinin, A E

    2016-03-01

    Noninvasive functional imaging holds great promise for the future of translational research, due to the ability to directly compare between preclinical and clinical models of psychiatric disorders. Despite this potential, concerns have been raised regarding the necessity to anesthetize rodent and monkey subjects during these procedures, because anesthetics may alter neuronal activity. For example, in studies on drugs of abuse and alcohol, it is not clear to what extent anesthesia can interfere with drug-induced neural activity. Therefore, the current study investigated whole-brain c-Fos activation following isoflurane anesthesia as well as ethanol-induced activation of c-Fos in anesthetized mice. In the first experiment, we examined effects of one or three sessions of gaseous isoflurane on c-Fos activation across the brain in male C57BL/6J mice. Isoflurane administration led to c-Fos activation in several areas, including the piriform cortex and lateral septum. Lower or similar levels of activation in these areas were detected after three sessions of isoflurane, suggesting that multiple exposures may eliminate some of the enhanced neuronal activation caused by acute isoflurane. In the second experiment, we investigated the ability of ethanol injection (1.5 or 2.5g/kgi.p.) to induce c-Fos activation under anesthesia. Following three sessions of isoflurane, 1.5g/kg of ethanol induced c-Fos in the central nucleus of amygdala and the centrally-projecting Edinger-Westphal nucleus (EWcp). This induction was lower after 2.5g/kg of ethanol. These results demonstrate that ethanol-induced neural activation can be detected in the presence of isoflurane anesthesia. They also suggest, that while habituation to isoflurane helps reduce neuronal activation, interaction between effects of anesthesia and alcohol can occur. Studies using fMRI imaging could benefit from using habituated animals and dose-response analyses. PMID:26742790

  1. Activity-dependent depression of neuronal sodium channels by the general anaesthetic isoflurane

    PubMed Central

    Purtell, K.; Gingrich, K. J.; Ouyang, W.; Herold, K. F.; Hemmings, H. C.

    2015-01-01

    Background The mechanisms by which volatile anaesthetics such as isoflurane alter neuronal function are poorly understood, in particular their presynaptic mechanisms. Presynaptic voltage-gated sodium channels (Nav) have been implicated as a target for anaesthetic inhibition of neurotransmitter release. We hypothesize that state-dependent interactions of isoflurane with Nav lead to increased inhibition of Na+ current (INa) during periods of high-frequency neuronal activity. Methods The electrophysiological effects of isoflurane, at concentrations equivalent to those used clinically, were measured on recombinant brain-type Nav1.2 expressed in ND7/23 neuroblastoma cells and on endogenous Nav in isolated rat neurohypophysial nerve terminals. Rate constants determined from experiments on the recombinant channel were used in a simple model of Nav gating. Results At resting membrane potentials, isoflurane depressed peak INa and shifted steady-state inactivation in a hyperpolarizing direction. After membrane depolarization, isoflurane accelerated entry (τcontrol=0.36 [0.03] ms compared with τisoflurane=0.33 [0.05] ms, P<0.05) and slowed recovery (τcontrol=6.9 [1.1] ms compared with τisoflurane=9.0 [1.9] ms, P<0.005) from apparent fast inactivation, resulting in enhanced depression of INa, during high-frequency stimulation of both recombinant and endogenous nerve terminal Nav. A simple model of Nav gating involving stabilisation of fast inactivation, accounts for this novel form of activity-dependent block. Conclusions Isoflurane stabilises the fast-inactivated state of neuronal Nav leading to greater depression of INa during high-frequency stimulation, consistent with enhanced inhibition of fast firing neurones. PMID:26089447

  2. Isoflurane modulates excitability in the mouse thalamus via GABA-dependent and GABA-independent mechanisms.

    PubMed

    Ying, Shui-Wang; Werner, David F; Homanics, Gregg E; Harrison, Neil L; Goldstein, Peter A

    2009-02-01

    GABAergic neurons in the reticular thalamic nucleus (RTN) synapse onto thalamocortical neurons in the ventrobasal (VB) thalamus, and this reticulo-thalamocortical pathway is considered an anatomic target for general anesthetic-induced unconsciousness. A mutant mouse was engineered to harbor two amino acid substitutions (S270H, L277A) in the GABA(A) receptor (GABA(A)-R) alpha1 subunit; this mutation abolished sensitivity to the volatile anesthetic isoflurane in recombinant GABA(A)-Rs, and reduced in vivo sensitivity to isoflurane in the loss-of-righting-reflex assay. We examined the effects of the double mutation on GABA(A)-R-mediated synaptic currents and isoflurane sensitivity by recording from thalamic neurons in brain slices. The double mutation accelerated the decay, and decreased the (1/2) width of, evoked inhibitory postsynaptic currents (eIPSCs) in VB neurons and attenuated isoflurane-induced prolongation of the eIPSC. The hypnotic zolpidem, a selective modulator of GABA(A)-Rs containing the alpha1 subunit, prolonged eIPSC duration regardless of genotype, indicating that mutant mice incorporate alpha1 subunit-containing GABA(A)-Rs into synapses. In RTN neurons, which lack the alpha1 subunit, eIPSC duration was longer than in VB, regardless of genotype. Isoflurane reduced the efficacy of GABAergic transmission from RTN to VB, independent of genotype, suggesting a presynaptic action in RTN neurons. Consistent with this observation, isoflurane inhibited both tonic action potential and rebound burst firing in the presence of GABA(A)-R blockade. The suppressed excitability in RTN neurons is likely mediated by isoflurane-enhanced Ba(2+)-sensitive, but 4-aminopyridine-insenstive, potassium conductances. We conclude that isoflurane enhances inhibition of thalamic neurons in VB via GABA(A)-R-dependent, but in RTN via GABA(A)-R-independent, mechanisms. PMID:18948126

  3. Anesthetics Isoflurane and Desflurane Differently Affect Mitochondrial Function, Learning, and Memory

    PubMed Central

    Zhang, Yiying; Xu, Zhipeng; Wang, Hui; Dong, Yuanlin; Shi, Hai Ning; Culley, Deborah J.; Crosby, Gregory; Marcantonio, Edward R.; Tanzi, Rudolph E.; Xie, Zhongcong

    2014-01-01

    Objective There are approximately 8.5 million Alzheimer disease (AD) patients who need anesthesia and surgery care every year. The inhalation anesthetic isoflurane, but not desflurane, has been shown to induce caspase activation and apoptosis, which are part of AD neuropathogenesis, through the mitochondria-dependent apoptosis pathway. However, the in vivo relevance, underlying mechanisms, and functional consequences of these findings remain largely to be determined. Methods We therefore set out to assess the effects of isoflurane and desflurane on mitochondrial function, cytotoxicity, learning, and memory using flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry, and the fear conditioning test. Results Here we show that isoflurane, but not desflurane, induces opening of mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, reduction in levels of mitochondrial membrane potential and adenosine-5′-triphosphate, activation of caspase 3, and impairment of learning and memory in cultured cells, mouse hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3 activation, and impairment of learning and memory. Finally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species. Interpretation These findings suggest that desflurane could be a safer anesthetic for AD patients as compared to isoflurane, and elucidate the potential mitochondria-associated underlying mechanisms, and therefore have implications for use of anesthetics in AD patients, pending human study confirmation. PMID:22368036

  4. Ventricular Arrhythmias and Mortality Associated with Isoflurane and Sevoflurane in a Porcine Model of Myocardial Infarction

    PubMed Central

    Regueiro-Purriños, Marta; Fernández-Vázquez, Felipe; de Prado, Armando Perez; Altónaga, Jose R; Cuellas-Ramón, Carlos; Ajenjo-Silverio, Jose M; Orden, Asuncion; Gonzalo-Orden, Jose M

    2011-01-01

    Ischemia of the myocardium can lead to reversible or irreversible injury depending on the severity and duration of the preceding ischemia. Here we compared sevoflurane and isoflurane with particular reference to their hemodynamic effects and ability to modify the effects of acute severe myocardial ischemia and reperfusion on ventricular arrhythmias and mortality in a porcine model of myocardial infarction. Female Large White pigs were premedicated with ketamine, midazolam, and atropine. Propofol was given intravenously for the anesthetic induction, and anesthesia was maintained with isoflurane or sevoflurane. Endovascular, fluoroscopy-guided, coronary procedures were performed to occlude the midleft anterior descending artery by using a coronary angioplasty balloon. After 75 min, the balloon catheter system was withdrawn and the presence of adequate reperfusion flow was verified. The pigs were followed for 2 mo, and overall mortality rate was calculated. The isoflurane group showed lower arterial pressure throughout the procedure, with the difference reaching statistical significance after induction of myocardial ischemia. The ventricular fibrillation rate was higher in isoflurane group (81.3%) than the sevoflurane group (51.7%; relative risk, 1.57 [1.03 to 2.4]). Overall survival was lower in the isoflurane group (75%) than the sevoflurane group (96.4%). In conclusion, in this porcine model of myocardial ischemia and reperfusion, sevoflurane was associated with higher hemodynamic stability and fewer ventricular arrhythmias and mortality than was isoflurane. PMID:21333167

  5. Isoflurane compared with fentanyl-midazolam-based anesthesia in patients undergoing heart transplantation

    PubMed Central

    Hsu, Che-Hao; Hsu, Yung-Chi; Huang, Go-Shine; Lu, Chih-Cherng; Ho, Shung-Tai; Liaw, Wen-Jinn; Tsai, Yi-Ting; Lin, Chih-Yuan; Tsai, Chien-Sung; Lin, Tso-Chou

    2016-01-01

    Abstract Inhalation anesthetics provide myocardial protection for cardiac surgery. This study was undertaken to compare the perioperative effects between isoflurane and fentanyl-midazolam-based anesthesia for heart transplantation. A retrospective cohort study was conducted by reviewing the medical records of heart transplantation in a single medical center from 1990 to 2013. Patients receiving isoflurane or fentanyl-midazolam-based anesthesia were included. Those with preoperative severe pulmonary, hepatic, or renal comorbidities were excluded. The perioperative variables and postoperative short-term outcomes were analyzed, including blood glucose levels, urine output, inotropic use, time to extubation, and length of stay in the intensive care units. After reviewing 112 heart transplantations, 18 recipients with fentanyl-midazolam-based anesthesia, and 29 receiving isoflurane anesthesia with minimal low-flow technique were analyzed. After cessation of cardiopulmonary bypass, recipients with isoflurane anesthesia had a significantly lower mean level and a less increase of blood glucose, as compared with those receiving fentanyl-based anesthesia. In addition, there was less use of dobutamine upon arriving the intensive care unit and a shorter time to extubation after isoflurane anesthesia. Compared with fentanyl-midazolam-based anesthesia, isoflurane minimal low-flow anesthesia maintained better perioperative homeostasis of blood glucose levels, less postoperative use of inotropics, and early extubation time among heart-transplant recipients without severe comorbidities. PMID:27583900

  6. Pulmonary alveolar proteinosis.

    PubMed

    Ioachimescu, O C; Kavuru, M S

    2006-01-01

    Pulmonary alveolar proteinosis is a rare syndrome characterized by intra-alveolar accumulation of surfactant components and cellular debris, with minimal interstitial inflammation or fibrosis. The condition has a variable clinical course, from spontaneous resolution to respiratory failure and death due to disease progression or superimposed infections. The standard of care for alveolor proteinosis therapy is represented by whole lung lavage. Important discoveries have been made in the last decade with respect to disease pathogenesis and therapy of both congenital and acquired forms of the disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway has been shown to be involved in the disease pathogenesis of both acquired and congenital disease. Furthermore, anti-GM-CSF blocking autoantibodies have been found in the serum and bronchoalveolar lavage fluid and seem to interfere with the surfactant clearance by alveolar macrophages in many acquired cases. In the congenital form, the most common defects identified to date are several mutations of the genes encoding GM-CSF receptor subunits or surfactant proteins. Using GM-CSF as a therapeutic tool has also been shown to be effective in at least half of the acquired cases treated, while the importance of quantitative determination of anti-GM-CSF antibodies before and during the course of the therapy, as well as the autoantibody titer-GM-CSF dose relationship are to be elucidated. The congenital form of the disease does not respond to therapy with GM-CSF, consistent with the known primary defects and differences in disease pathogenesis. PMID:16916009

  7. Alveolar Capillary Dysplasia

    PubMed Central

    Stankiewicz, Pawel; Steinhorn, Robin H.

    2011-01-01

    Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare, fatal developmental lung disorder of neonates and infants. This review aims to address recent findings in the etiology and genetics of ACD/MPV and to raise awareness of this poorly known disease, which may also present as milder, unclassified forms. Successively discussed are what is known about the epidemiology, pathogenesis, pathophysiology, diagnostic indicators and approaches, genetic testing, treatment, and cases of delayed onset. The review concludes with suggestions for future directions to answer the many unknowns about this disorder. PMID:21471096

  8. Alveolar rhabdomyosarcoma of maxilla

    PubMed Central

    Ananthaneni, Anuradha; Kuberappa, Puneeth Horatti; Srinivas, G Vijay; Kiresur, Mohammad Asif

    2016-01-01

    Rhabdomyosarcoma (RMS), a malignant neoplasm of skeletal muscle origin, is the most common soft tissue sarcoma seen in childhood and adolescence. The most frequent site is the head and neck accounting for 40% of all cases and other involved sites are genitourinary tract, retroperitoneum, and to a lesser extent, the extremities. RMS is relatively uncommon in the oral cavity and the involvement of the jaws is extremely rare. Here, we report a case of 50-year-old female with oral RMS involving maxillary alveolar region with clinical, radiological, histopathological and immunohistochemical findings. PMID:27194887

  9. Alveolar rhabdomyosarcoma of maxilla.

    PubMed

    Ananthaneni, Anuradha; Kuberappa, Puneeth Horatti; Srinivas, G Vijay; Kiresur, Mohammad Asif

    2016-01-01

    Rhabdomyosarcoma (RMS), a malignant neoplasm of skeletal muscle origin, is the most common soft tissue sarcoma seen in childhood and adolescence. The most frequent site is the head and neck accounting for 40% of all cases and other involved sites are genitourinary tract, retroperitoneum, and to a lesser extent, the extremities. RMS is relatively uncommon in the oral cavity and the involvement of the jaws is extremely rare. Here, we report a case of 50-year-old female with oral RMS involving maxillary alveolar region with clinical, radiological, histopathological and immunohistochemical findings. PMID:27194887

  10. Pulmonary Alveolar Proteinosis Syndrome.

    PubMed

    Suzuki, Takuji; Trapnell, Bruce C

    2016-09-01

    Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by the accumulation of surfactant in alveoli and terminal airways resulting in respiratory failure. PAP comprises part of a spectrum of disorders of surfactant homeostasis (clearance and production). The surfactant production disorders are caused by mutations in genes required for normal surfactant production. The PAP syndrome is identified based on history, radiologic, and bronchoalveolar lavage and/or histopathologic findings. The diagnosis of PAP-causing diseases in secondary PAP requires further studies. Whole-lung lavage is the current standard therapy and promising new pharmacologic therapies are in development. PMID:27514590

  11. Pulmonary Alveolar Microlithiasis

    PubMed Central

    Mehta, Kevan; Dell, Sharon; Birken, Catherine; Al-Saleh, Suhail

    2016-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive condition that is often asymptomatic despite significant changes in chest imaging. Diagnosis is often made when patients become symptomatic in adulthood. There are still no proven treatments, but earlier diagnosis may allow for evaluation of preventative strategies that could improve outcome. It is an important diagnosis to consider in children who have marked radiographic findings with no or very mild symptoms or physical findings. Diagnosis can be made with imaging alone but may necessitate lung biopsy for definitive diagnosis. PMID:27445543

  12. Postnatal Isoflurane Exposure Induces Cognitive Impairment and Abnormal Histone Acetylation of Glutamatergic Systems in the Hippocampus of Adolescent Rats.

    PubMed

    Liang, Bing; Fang, Jie

    2016-09-01

    Isoflurane can elicit cognitive impairment. However, the pathogenesis in the brain remains inconclusive. The present study investigated the mechanism of glutamate neurotoxicity in adolescent male rats that underwent postnatal isoflurane exposure and the role of sodium butyrate (NaB) in cognitive impairment induced by isoflurane exposure. Seven-day-old rats were exposed to 1.7 % isoflurane for 35 min every day for four consecutive days, and then glutamate neurotoxicity was examined in the hippocampus. Morris water maze analysis showed cognitive impairments in isoflurane-exposed rats. High-performance liquid chromatography found higher hippocampal glutamate concentrations following in vitro and in vivo isoflurane exposure. The percentage of early apoptotic hippocampal neurons was markedly increased after isoflurane exposure. Decreased acetylation and increased HDAC2 activity were observed in the hippocampus of isoflurane-exposed rats and hippocampal neurons. Furthermore, postnatal isoflurane exposure decreased histone acetylation of hippocampal neurons in the promoter regions of GLT-1 and mGLuR1/5, but not mGLuR2/3. Treatment with NaB not only restored the histone acetylation of the GLT-1 and mGLuR1/5 promoter regions and glutamate excitatory neurotoxicity in hippocampal neurons, but also improved cognitive impairment in vivo. Moreover, NaB may be a potential therapeutic drug for cognitive impairment caused by isoflurane exposure. These results suggest that postnatal isoflurane exposure contributes to cognitive impairment via decreasing histone acetylation of glutamatergic systems in the hippocampus of adolescent rats. PMID:27307148

  13. Alveolar bone grafting

    PubMed Central

    Lilja, Jan

    2009-01-01

    In patients with cleft lip and palate, bone grafting in the mixed dentition in the residual alveolar cleft has become a well-established procedure. The main advantages can be summarised as follows: stabilisation of the maxillary arch; facilitation of eruption of the canine and sometimes facilitation of the lateral incisor eruption; providing bony support to the teeth adjacent to the cleft; raising the alar base of the nose; facilitation of closure of an oro-nasal fistula; making it possible to insert a titanium fixture in the grafted site and to obtain favourable periodontal conditions of the teeth within and adjacent to the cleft. The timing of the ABG surgery take into consideration not only eruption of the canine but also that of the lateral incisor, if present. The best time for bone grafting surgery is when a thin shell of bone still covers the soon erupting lateral incisor or canine tooth close to the cleft. PMID:19884665

  14. Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain

    PubMed Central

    2016-01-01

    Abstract What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multielectrode technique, we recorded local field potentials from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli (‘frequency tags’) allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17 Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice the tag frequency (26 or 34 Hz) in the optic lobes of the fly, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted signal-to-noise ratios. Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain. PMID:27517084

  15. Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain.

    PubMed

    Cohen, Dror; Zalucki, Oressia H; van Swinderen, Bruno; Tsuchiya, Naotsugu

    2016-01-01

    What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multielectrode technique, we recorded local field potentials from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli ('frequency tags') allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17 Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice the tag frequency (26 or 34 Hz) in the optic lobes of the fly, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted signal-to-noise ratios. Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain. PMID:27517084

  16. Isoflurane compared with midazolam for sedation in the intensive care unit.

    PubMed Central

    Kong, K. L.; Willatts, S. M.; Prys-Roberts, C.

    1989-01-01

    OBJECTIVE--To compare isoflurane with midazolam for sedation of ventilated patients. DESIGN--Randomised control study. Setting--Intensive care unit in university teaching hospital. PATIENTS--Sixty patients aged 18-76 who required mechanical ventilation. INTERVENTIONS--Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous intravenous infusion of midazolam 0.01-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required. The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours (whichever was earlier). END POINT--Achievement of a predetermined level of sedation for as much of the time as possible. MAIN RESULTS--Isoflurane produced satisfactory sedation for a greater proportion of time (86%) than midazolam (64%), and patients sedated with isoflurane recovered more rapidly from sedation. CONCLUSION--Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit. PMID:2500195

  17. Electrical stimulation of the parabrachial nucleus induces reanimation from isoflurane general anesthesia.

    PubMed

    Muindi, Fanuel; Kenny, Jonathan D; Taylor, Norman E; Solt, Ken; Wilson, Matthew A; Brown, Emery N; Van Dort, Christa J

    2016-06-01

    Clinically, emergence from general anesthesia is viewed as a passive process where anesthetics are discontinued at the end of surgery and anesthesiologists wait for the drugs to wear off. The mechanisms involved in emergence are not well understood and there are currently no drugs that can actively reverse the state of general anesthesia. An emerging hypothesis states that brain regions that control arousal become active during emergence and are a key part of the return to wakefulness. In this study, we tested the hypothesis that electrical activation of the glutamatergic parabrachial nucleus (PBN) in the brainstem is sufficient to induce reanimation (active emergence) during continuous isoflurane general anesthesia. Using c-Fos immunohistochemistry as a marker of neural activity, we first show a selective increase in active neurons in the PBN during passive emergence from isoflurane anesthesia. We then electrically stimulated the PBN to assess whether it is sufficient to induce reanimation from isoflurane general anesthesia. Stimulation induced behavioral arousal and restoration of the righting reflex during continuous isoflurane general anesthesia. In contrast, stimulation of the nearby central inferior colliculus (CIC) did not restore the righting reflex. Spectral analysis of the electroencephalogram (EEG) revealed that stimulation produced a significant decrease in EEG delta power during PBN stimulation. The results are consistent with the hypothesis that the PBN provides critical arousal input during emergence from isoflurane anesthesia. PMID:26971629

  18. The volatile anesthetic isoflurane induces ecto-5′-nucleotidase (CD73) to protect against renal ischemia and reperfusion injury

    PubMed Central

    Kim, Mihwa; Ham, Ahrom; Kim, Joo Yun; Brown, Kevin M.; D’Agati, Vivette D.; Lee, H. Thomas

    2013-01-01

    The volatile anesthetic isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-β1. Since adenosine is a powerful cytoprotective molecule, we tested whether TGF-β1 generated by isoflurane induces renal tubular ecto-5′-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. Moreover, a TGF-β1 neutralizing antibody prevented isoflurane-mediated induction of CD73 activity. Mice anesthetized with isoflurane after renal ischemia and reperfusion had significantly reduced plasma creatinine and decreased renal tubular necrosis, neutrophil infiltration and apoptosis compared to pentobarbital-anesthetized mice. Isoflurane failed to protect against renal ischemia and reperfusion injury in CD73 deficient mice, in mice pretreated with a selective CD73 inhibitor or mice treated with an adenosine receptor antagonist. The TGF-β1 neutralizing antibody or the CD73 inhibitor attenuated isoflurane-mediated protection against HK-2 cell apoptosis. Thus, isoflurane causes TGF-β1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury. PMID:23423261

  19. Changes in circulating blood volume following isoflurane or sevoflurane anesthesia.

    PubMed

    Hamada, H; Takaori, M; Kimura, K; Fukui, A; Fujita, Y

    1993-07-01

    Changes of circulating blood volume (CB volume) measured by the dual indicator dilution method were observed in 33 chronically instrumented mongrel dogs following either alpha-chloralose-urethane (C group), additive isoflurane (I group) or sevoflurane anesthesia (S group). These anesthetic groups were each divided into two subgroups with regard to respiratory care, namely Cp, Ip and Sp for those with intermittent positive pressure ventilation (six animals per subgroups), and Cs, Is and Ss for those with spontaneous breathing (five animals per subgroups). The CB volume under positive pressure ventilation remained unchanged in the Ip and Sp groups at both 0.5 and 1.0 MAC, and in the Cp group. The CB volume remained essentially unchanged in the Cs and Is groups at both 0.5 or 1.0 MAC, but the plasma volume tended to increase slightly in the Is group at 1.0 MAC. In the Ss group under spontaneous breathing, however, the CB volume increased from 84.4 +/- 7.0 to 91.4 +/- 7.7 at 0.5 MAC, and to 91.4 +/- 10.2 ml.kg(-1) at 1.0 MAC (0.01 < P < 0.05). These increases were caused by an increase in the plasma volume. The above data suggests that a concomitant increase in the venous pressure associated with an increase in the intrathoracic pressure produced by positive pressure ventilation would attenuate changes in the CB volume during sevoflurane anesthesia. PMID:15278818

  20. Pupil Size in Relation to Cortical States during Isoflurane Anesthesia

    PubMed Central

    Kum, Jeung Eun; Han, Hio-Been

    2016-01-01

    In neuronal recording studies on anesthetized animals, reliable measures for the transitional moment of consciousness are frequently required. Previous findings suggest that pupil fluctuations reflect the neuronal states during quiet wakefulness, whose correlation was unknown for the anesthetized condition. Here, we investigated the pupillary changes under isoflurane anesthesia simultaneously with the electroencephalogram (EEG) and electromyogram (EMG). The pupil was tracked by using a region-based active contour model. The dose was given to the animal in a stepwise increasing mode (simulating induction of anesthesia) or in a stepwise decreasing mode (simulating emergence of anesthesia). We found that the quickly widening pupil action (mydriasis) characterizes the transitional state in anesthesia. Mydriasis occurred only in the light dose in the emergence phase, and the events were accompanied by an increase of burst activity in the EEG followed by EMG activity in 47% of the mydriasis events. Our findings suggest that recording such pupil changes may offer a noncontact monitoring tool for indexing the transitional state of the brain, particularly when a lower threshold dose is applied. PMID:27122995

  1. Comparison of isoflurane and carbon dioxide anesthesia in Chilean rose tarantulas (Grammostola rosea).

    PubMed

    Dombrowski, Daniel S; De Voe, Ryan S; Lewbart, Gregory A

    2013-01-01

    This study investigated the use of two anesthetic agents, isoflurane and carbon dioxide, in Chilean rose tarantulas (Grammostola rosea). We compared the onset, duration of anesthesia, and recovery time with both gases, and made observations regarding the effects of the anesthetic protocols. Subjectively, episodes for the isoflurane animals were uneventful. The spiders were calm throughout and did not respond adversely to gas exposure. Conversely, animals anesthetized with carbon dioxide experienced violent inductions and recoveries; the tarantulas appeared agitated when the carbon dioxide flow began. Seizure-like activity and defecation would frequently be noted prior to induction with carbon dioxide. Neither isoflurane nor carbon dioxide seemed to have any clinically apparent short- or long-term impact. The animals were all normal for at least 1-year postexperiment. Future studies should focus on defining the impact, if any, that these anesthetic agents have on the health of invertebrate species. PMID:22730146

  2. PPARs in alveolar macrophage biology.

    PubMed

    Smith, Monica R; Standiford, Theodore J; Reddy, Raju C

    2007-01-01

    PPARs, most notably PPAR-gamma, play a crucial role in regulating the activation of alveolar macrophages, which in turn occupy a pivotal place in the immune response to pathogens and particulates drawn in with inspired air. In this review, we describe the dual role of the alveolar macrophage as both a first-line defender through its phagocytotic activity and a regulator of the immune response. Depending on its state of activation, the alveolar macrophage may either enhance or suppress different aspects of immune function in the lung. We then review the role of PPAR-gamma and its ligands in deactivating alveolar macrophages-thus limiting the inflammatory response that, if unchecked, could threaten the essential respiratory function of the alveolus-while upregulating the cell's phagocytotic activity. Finally, we examine the role that inadequate or inappropriate PPAR-gamma responses play in specific lung diseases. PMID:18000531

  3. Phenylephrine does not limit myocardial blood flow or oxygen delivery during isoflurane-induced hypotension in dogs.

    PubMed

    Abdel-Latif, M; Kim, S J; Salem, M R; Crystal, G J

    1992-06-01

    Experiments were performed on seven fentanyl-pentobarbital-anesthetized, open-chest dogs to determine whether stimulation of coronary alpha 1-adrenergic receptors by phenylephrine causes coronary vasoconstriction and impaired myocardial oxygen delivery when phenylephrine is infused to correct isoflurane-induced hypotension. Myocardial blood flow was measured with radioactive microspheres, and myocardial oxygen and lactate extraction were determined. The Fick equation was used to calculate myocardial oxygen consumption. Measurements were obtained (a) under control conditions, (b) after a 30-min inhalation of isoflurane sufficient to decrease mean aortic pressure by 30%, and (c) while maintaining administration of isoflurane, 5-10 min after restoration of mean aortic pressure by intravenous infusion of phenylephrine. Isoflurane-induced hypotension was accompanied by a baroreceptor-mediated increase in heart rate and by a decrease in myocardial oxygen consumption; however, myocardial blood flow was maintained, resulting in decreased oxygen extraction and increased coronary sinus PO2, thus implying a direct coronary vasodilating effect for isoflurane. Lactate extraction was unaffected. Phenylephrine infusion during inhalation of isoflurane returned mean aortic pressure and heart rate to their respective control values, and it did not change myocardial oxygen consumption, myocardial blood flow, myocardial oxygen extraction, coronary sinus PO2, or lactate extraction from values obtained during isoflurane alone. These latter findings are consistent with undiminished coronary vasodilation by isoflurane in the presence of phenylephrine. In conclusion, infused phenylephrine to restore aortic pressure during isoflurane administration had no vasoconstrictor effect in the coronary circulation and did not impair myocardial oxygen delivery. Apparently, the direct coronary vasodilating action of isoflurane completely nullified phenylephrine-induced vasoconstriction via local alpha

  4. Isoflurane Exposure during Mid-Adulthood Attenuates Age-Related Spatial Memory Impairment in APP/PS1 Transgenic Mice

    PubMed Central

    Xu, Huan; Wang, Beilei; Chen, Xuemei; Chen, Jie; Wang, Xiangrui

    2012-01-01

    Many in vitro findings suggest that isoflurane exposure might accelerate the process of Alzheimer Disease (AD); however, no behavioral evidence exists to support this theory. In the present study, we hypothesized that exposure of APP/PS1 transgenic mice to isoflurane during mid-adulthood, which is the pre-symptomatic phase of amyloid beta (Abeta) deposition, would alter the progression of AD. Seven-month-old Tg(APPswe,PSEN1dE9)85Dbo/J transgenic mice and their wild-type littermates were exposed to 1.1% isoflurane for 2 hours per day for 5 days. Learning and memory ability was tested 48 hours and 5 months following isoflurane exposure using the Morris Water Maze and Y maze, respectively. Abeta deposition and oligomers in the hippocampus were measured by immunohistochemistry or Elisa 5 months following isoflurane exposure. We found that the performance of both the transgenic and wild-type mice in the Morris Water Maze significantly improved 48 hours following isoflurane exposure. The transgenic mice made significantly fewer discrimination errors in the Y maze following isoflurane exposure, and no differences were found between wild-type littermates 5 months following isoflurane exposure. For the transgenic mice, the Abeta plaque and oligomers in the hippocampus was significantly decreased in the 5 months following isoflurane exposure. In summary, repeated isoflurane exposure during the pre-symptomatic phase not only improved spatial memory in both the APP/PS1 transgenic and wild-type mice shortly after the exposure but also prevented age-related decline in learning and memory and attenuated the Abeta plaque and oligomers in the hippocampus of transgenic mice. PMID:23185565

  5. Solar Minimum

    NASA Astrophysics Data System (ADS)

    Lopresto, James C.; Mathews, John; Manross, Kevin

    1995-12-01

    Calcium K plage, H alpha plage and sunspot area have been monitored daily on the INTERNET since November of 1992. The plage and sunspot area have been measured by image processing. The purpose of the project is to investigate the degree of correlation between plage area and solar irradiance. The plage variation shows the expected variation produced by solar rotation and the longer secular changes produced by the solar cycle. The H alpha and sunspot plage area reached a minimum in about late 1994 or early 1995. This is in agreement with the K2 spectral index obtained daily from Sacramento Peak Observatory. The Calcium K plage area minimum seems delayed with respect to the others mentioned above. The minimum of the K line plage area is projected to come within the last few months of 1995.

  6. Micronuclei in human alveolar macrophages.

    PubMed

    D'Agostini, F; Bonatti, S; Oddera, S; De Flora, S

    1992-01-01

    Occurrence of micronuclei was monitored in pulmonary alveolar macrophages collected from 31 individuals undergoing diagnostic bronchoalveolar lavage. The overall frequency of micronucleated cells was 3.88 +/- 1.84/1000, without any significant difference attributable to sex, age, pathology, occupation, or smoking habits. The lack of influence of cigarette smoke on this clastogenicity index presumably reflects the very low rate of mitoses of macrophages in the alveolar lumen. PMID:1579732

  7. Strain differences in cortical electroencephalogram associated with isoflurane-induced loss of consciousness

    PubMed Central

    McCallum, J. Bruce; Pillay, Siveshigan; Vizuete, Jeannette A.; Mouradian, Gary; Hudetz, Anthony G.; Stekiel, Thomas A.

    2014-01-01

    Introduction Previously observed increased sensitivity to noxious stimulation in the Dahl salt-sensitive rat strain (SS/JrHsdMcwi, abbreviated as SS) compared to Brown Norway rats (BN/NhsdMcwi abbreviated as BN) is mediated by gene(s) on a single chromosome. The present study used behavioral and electrocortical data to determine if differences also exist between SS and BN in loss of consciousness. Methods Behavioral responses, including loss of righting, (a putative index of consciousness) and concurrent electroencephalogram recordings, in twelve SS and BN rats were measured during isoflurane at inhaled concentrations of 0, 0.3, 0.6, 0.8, 1.0 and 1.2%. Results In SS compared to BN, the mean ± SEM EC50 for righting was significantly less (0.65 ± 0.01% vs 0.74 ± 0.02% inhaled isoflurane) and delta fraction in parietal electroencephalogram was enhanced 50 - 100% at all isoflurane levels during emergence. The frequency decay constant of the exponential fit of parietal electroencephalogram spectrum graphed as a function of isoflurane level was 3 times less steep (mean ± SEM slope −57 ± 13 vs −191 ± 38) and lower at each level of isoflurane in SS vs BN (i.e. shifted toward low frequency activity). Electroencephalogram differences between strains were larger during emergence than induction. Conclusions Sensitivity is higher in SS compared to BN leading to unconsciousness at lower levels of isoflurane. This supports using additional strains in this animal model to study the genetic basis for differences in anesthetic action on mechanisms of consciousness. Moreover, induction and emergence appear to involve distinct pathways. PMID:23287707

  8. Neonatal Isoflurane Exposure Induces Neurocognitive Impairment and Abnormal Hippocampal Histone Acetylation in Mice

    PubMed Central

    Zhong, Tao; Guo, Qulian; Zou, Wangyuan; Zhu, Xiaoyan; Song, Zongbin; Sun, Bei; He, Xin; Yang, Yong

    2015-01-01

    Background Neonatal exposure to isoflurane may induce long-term memory impairment in mice. Histone acetylation is an important form of chromatin modification that regulates the transcription of genes required for memory formation. This study investigated whether neonatal isoflurane exposure-induced neurocognitive impairment is related to dysregulated histone acetylation in the hippocampus and whether it can be attenuated by the histone deacetylase (HDAC) inhibitor trichostatin A (TSA). Methods C57BL/6 mice were exposed to 0.75% isoflurane three times (each for 4 h) at postnatal days 7, 8, and 9. Contextual fear conditioning (CFC) was tested at 3 months after anesthesia administration. TSA was intraperitoneally injected 2 h before CFC training. Hippocampal histone acetylation levels were analyzed following CFC training. Levels of the neuronal activation and synaptic plasticity marker c-Fos were investigated at the same time point. Results Mice that were neonatally exposed to isoflurane showed significant memory impairment on CFC testing. These mice also exhibited dysregulated hippocampal H4K12 acetylation and decreased c-Fos expression following CFC training. TSA attenuated isoflurane-induced memory impairment and simultaneously increased histone acetylation and c-Fos levels in the hippocampal cornu ammonis (CA)1 area 1 h after CFC training. Conclusions Memory impairment induced by repeated neonatal exposure to isoflurane is associated with dysregulated histone H4K12 acetylation in the hippocampus, which probably affects downstream c-Fos gene expression following CFC training. The HDAC inhibitor TSA successfully rescued impaired contextual fear memory, presumably by promoting histone acetylation and histone acetylation-mediated gene expression. PMID:25928815

  9. Isoflurane and Propofol Contribute to Increasing the Antioxidant Status of Patients During Minor Elective Surgery

    PubMed Central

    Braz, Mariana G.; Braz, Leandro G.; Freire, Cristiana M.M.; Lucio, Lorena M.C.; Braz, José R.C.; Tang, Guangwen; Salvadori, Daisy M.F.; Yeum, Kyung-Jin

    2015-01-01

    Abstract Isoflurane is a volatile halogenated anesthetic used especially for anesthesia maintenance whereas propofol is a venous anesthetic utilized for anesthesia induction and maintenance, and reportedly an antioxidant. However, there are still controversies related to isoflurane-induced oxidative stress and it remains unanswered whether the antioxidant effects occur in patients under propofol anesthesia. Taking into account the importance of better understanding the role of anesthetics on oxidative stress in anesthetized patients, the present study was designed to evaluate general anesthesia maintained with isoflurane or propofol on antioxidant status in patients who underwent minimally invasive surgeries. We conducted a prospective randomized trial in 30 adult patients without comorbidities who underwent elective minor surgery (septoplasty) lasting at least 2 h admitted to a Brazilian tertiary hospital. The patients were randomly allocated into 2 groups, according to anesthesia maintenance (isoflurane, n = 15 or propofol, n = 15). Peripheral blood samples were drawn before anesthesia (baseline) and 2-h after anesthesia induction. The primary outcomes were to investigate the effect of either isoflurane or propofol anesthesia on aqueous plasma oxidizability and total antioxidant performance (TAP) by fluorometry as well as several individual antioxidants by high-performance liquid chromatography. As secondary outcome, oxidized genetic damage (7,8-dihydro-8-oxoguanine, known as 8-oxo-Gua) was investigated by the comet assay. Both anesthesia techniques (isoflurane or propofol) for a 2-h period resulted in a significant decrease of plasma α-tocopherol, but not other antioxidants including uric acid, carotenoids, and retinol (P > 0.05). Propofol, in contrast to isoflurane anesthesia, significantly increased (P < 0.001) anti-inflammatory/antioxidant plasma γ-tocopherol concentration in patients. Both anesthesia types significantly enhanced

  10. Inferior alveolar nerve repositioning.

    PubMed

    Louis, P J

    2001-09-01

    Nerve repositioning is a viable alternative for patients with an atrophic edentulous posterior mandible. Patients, however, should be informed of the potential risks of neurosensory disturbance. Documentation of the patient's baseline neurosensory function should be performed with a two-point discrimination test or directional brush stroke test preoperatively and postoperatively. Recovery of nerve function should be expected in 3 to 6 months. The potential for mandibular fracture when combining nerve repositioning with implant placement also should be discussed with the patient. This can be avoided by minimizing the amount of buccal cortical plate removal during localization of the nerve and maintaining the integrity of the inferior cortex of the mandible. Additionally, avoid overseating the implant, thus avoiding stress along the inferior border of the mandible. The procedure does allow for the placement of longer implants, which should improve implant longevity. Patients undergoing this procedure have expressed overall satisfaction with the results. Nerve repositioning also can be used to preserve the inferior alveolar nerve during resection of benign tumors or cysts of the mandible. This procedure allows the surgeon to maintain nerve function in situations in which the nerve would otherwise have to be resected. PMID:11665379

  11. Micromechanics of alveolar edema.

    PubMed

    Perlman, Carrie E; Lederer, David J; Bhattacharya, Jahar

    2011-01-01

    The decrease of lung compliance in pulmonary edema underlies ventilator-induced lung injury. However, the cause of the decrease in compliance is unknown. We tested the hypothesis that in pulmonary edema, the mechanical effects of liquid-filled alveoli increase tissue stress in adjacent air-filled alveoli. By micropuncture of isolated, perfused rat lungs, we established a single-alveolus model of pulmonary edema that we imaged using confocal microscopy. In this model, we viewed a liquid-filled alveolus together with its air-filled neighbor at different transpulmonary pressures, both before and after liquid-filling. Instilling liquid in an alveolus caused alveolar shrinkage. As a result, the interalveolar septum was stretched, causing the neighboring air-filled alveolus to bulge. Thus, the air-filled alveolus was overexpanded by virtue of its adjacency to a liquid-filled alveolus. Confocal microscopy at different depths of the liquid-filled alveolus revealed a meniscus. Lung inflation to near-total lung capacity (TLC) demonstrated decreased compliance of the air-filled but not liquid-filled alveolus. However, at near TLC, the air-filled alveolus was larger than it was in the pre-edematous control tissue. In pulmonary edema, liquid-filled alveoli induce mechanical stress on air-filled alveoli, reducing the compliance of air-filled alveoli, and hence overall lung compliance. Because of increased mechanical stress, air-filled alveoli may be susceptible to overdistension injury during mechanical ventilation of the edematous lung. PMID:20118224

  12. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity.

    PubMed

    Westphalen, Kristin; Gusarova, Galina A; Islam, Mohammad N; Subramanian, Manikandan; Cohen, Taylor S; Prince, Alice S; Bhattacharya, Jahar

    2014-02-27

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca(2+) waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca(2+)-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation. PMID:24463523

  13. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    NASA Astrophysics Data System (ADS)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  14. Isoflurane Is More Deleterious to Developing Brain Than Desflurane: The Role of the Akt/GSK3β Signaling Pathway

    PubMed Central

    Tao, Guorong; Xue, Qingsheng; Luo, Yan; Li, Guohui; Xia, Yimeng; Yu, Buwei

    2016-01-01

    Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3β signaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3β and learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3β and learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3β (ser9) expressions, which led to GSK3β overactivation. Lithium prevented GSK3β overactivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3β signaling pathway partly participates in this process. GSK3β inhibition might be an effective way to protect against developmental neurotoxicity. PMID:27057548

  15. Anesthetic effects of isoflurane on the tonotopic map and neuronal population activity in the rat auditory cortex.

    PubMed

    Noda, Takahiro; Takahashi, Hirokazu

    2015-09-01

    Since its discovery nearly four decades ago, sequential microelectrode mapping using hundreds of recording sites has been able to reveal a precise tonotopic organization of the auditory cortex. Despite concerns regarding the effects that anesthesia might have on neuronal responses to tones, anesthesia was essential for these experiments because such dense mapping was elaborate and time-consuming. Here, taking an 'all-at-once' approach, we investigated how isoflurane modifies spatiotemporal activities by using a dense microelectrode array. The array covered the entire auditory cortex in rats, including the core and belt cortices. By comparing neuronal activity in the awake state with activity under isoflurane anesthesia, we made four observations. First, isoflurane anesthesia did not modify the tonotopic topography within the auditory cortex. Second, in terms of general response properties, isoflurane anesthesia decreased the number of active single units and increased their response onset latency. Third, in terms of tuning properties, isoflurane anesthesia shifted the response threshold without changing the shape of the frequency response area and decreased the response quality. Fourth, in terms of population activities, isoflurane anesthesia increased the noise correlations in discharges and phase synchrony in local field potential (LFP) oscillations, suggesting that the anesthesia made neuronal activities redundant at both single-unit and LFP levels. Thus, while isoflurane anesthesia had little effect on the tonotopic topography, its profound effects on neuronal activities decreased the encoding capacity of the auditory cortex. PMID:26118739

  16. Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC

    PubMed Central

    Chen, Qiang; Kinde, Monica N.; Arjunan, Palaniappa; Wells, Marta M.; Cohen, Aina E.; Xu, Yan; Tang, Pei

    2015-01-01

    Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6′) and A244(13′). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6′ or 13′ support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs. PMID:26346220

  17. Hereditary Pulmonary Alveolar Proteinosis

    PubMed Central

    Suzuki, Takuji; Sakagami, Takuro; Young, Lisa R.; Carey, Brenna C.; Wood, Robert E.; Luisetti, Maurizio; Wert, Susan E.; Rubin, Bruce K.; Kevill, Katharine; Chalk, Claudia; Whitsett, Jeffrey A.; Stevens, Carrie; Nogee, Lawrence M.; Campo, Ilaria; Trapnell, Bruce C.

    2010-01-01

    Rationale: We identified a 6-year-old girl with pulmonary alveolar proteinosis (PAP), impaired granulocyte-macrophage colony–stimulating factor (GM-CSF) receptor function, and increased GM-CSF. Objectives: Increased serum GM-CSF may be useful to identify individuals with PAP caused by GM-CSF receptor dysfunction. Methods: We screened 187 patients referred to us for measurement of GM-CSF autoantibodies to diagnose autoimmune PAP. Five were children with PAP and increased serum GM-CSF but without GM-CSF autoantibodies or any disease causing secondary PAP; all were studied with family members, subsequently identified patients, and controls. Measurement and Main Results: Eight children (seven female, one male) were identified with PAP caused by recessive CSF2RA mutations. Six presented with progressive dyspnea of insidious onset at 4.8 ± 1.6 years and two were asymptomatic at ages 5 and 8 years. Radiologic and histopathologic manifestations were similar to those of autoimmune PAP. Molecular analysis demonstrated that GM-CSF signaling was absent in six and severely reduced in two patients. The GM-CSF receptor β chain was detected in all patients, whereas the α chain was absent in six and abnormal in two, paralleling the GM-CSF signaling defects. Genetic analysis revealed multiple distinct CSF2RA abnormalities, including missense, duplication, frameshift, and nonsense mutations; exon and gene deletion; and cryptic alternative splicing. All symptomatic patients responded well to whole-lung lavage therapy. Conclusions: CSF2RA mutations cause a genetic form of PAP presenting as insidious, progressive dyspnea in children that can be diagnosed by a combination of characteristic radiologic findings and blood tests and treated successfully by whole-lung lavage. PMID:20622029

  18. Critical Role of Interleukin-11 in Isoflurane-mediated Protection against Ischemic Acute Kidney Injury in Mice

    PubMed Central

    Ham, Ahrom; Kim, Mihwa; Kim, Joo Yun; Brown, Kevin M.; Yeh, James; D’Agati, Vivette D.; Lee, H. Thomas

    2013-01-01

    Background Isoflurane releases renal tubular transforming growth factor-beta 1 (TGF-β1) and protects against ischemic acute kidney injury (AKI). Recent studies suggest that TGF-β1 can induce a cytoprotective cytokine interleukin (IL)-11. Here, we tested the hypothesis that isoflurane protects against ischemic AKI by direct induction of renal tubular IL-11 synthesis. Methods Human kidney proximal tubule (HK-2) cells were treated with 1.25-2.5% isoflurane or carrier gas (room air+5% carbon dioxide) for 0-16 h. We also anesthetized C57BL/6 mice with 1.2% isoflurane or with equi-anesthetic dose of pentobarbital for 4 h. In addition, we subjected IL-11 receptor (IL-11R) wild type, IL-11R deficient or IL-11 neutralized mice to 30-min renal ischemia followed by reperfusion under 4 h of pentobarbital or isoflurane (1.2%) anesthesia. Results Isoflurane increased IL-11 synthesis in human (~300-500% increase, N = 6) and mouse (23 ± 4 (mean ± SD) fold over carrier gas group, N = 4) proximal tubule cells that were attenuated by a TGF-β1 neutralizing antibody. Mice anesthetized with isoflurane showed significantly increased kidney IL-11 messenger RNA (13.8 ± 2 fold over carrier gas group, N = 4) and protein (31 ± 9 vs. 18±2 pg/mg protein or ~80% increase, N = 4) expression compared to pentobarbital anesthetized mice and this increase was also attenuated by a TGF-β1 neutralizing antibody. Furthermore, isoflurane-mediated renal protection in IL-11R wild-type mice were absent in IL-11R deficient mice or in IL-11R wild-type mice treated with IL-11 neutralizing antibody (N = 4-6). Conclusions Our studies suggest that isoflurane induces renal tubular IL-11 via TGF-β1 signaling to protect against ischemic AKI. PMID:24037316

  19. Isoflurane-Induced Caspase-3 Activation Is Dependent on Cytosolic Calcium and Can Be Attenuated by Memantine

    PubMed Central

    Zhang, Guohua; Dong, Yuanlin; Zhang, Bin; Ichinose, Fumito; Wu, Xu; Culley, Deborah J.; Crosby, Gregory

    2008-01-01

    Increasing evidence indicates that caspase activation and apoptosis are associated with a variety of neurodegenerative disorders, including Alzheimer's disease. We reported that anesthetic isoflurane can induce apoptosis, alter processing of the amyloid precursor protein (APP), and increase amyloid-β protein (Aβ) generation. However, the mechanism by which isoflurane induces apoptosis is primarily unknown. We therefore set out to assess effects of extracellular calcium concentration on isoflurane-induced caspase-3 activation in H4 human neuroglioma cells stably transfected to express human full-length APP (H4-APP cells). In addition, we tested effects of RNA interference (RNAi) silencing of IP3 receptor, NMDA receptor, and endoplasmic reticulum (ER) calcium pump, sacro-/ER calcium ATPase (SERCA1). Finally, we examined the effects of the NMDA receptor partial antagonist, memantine, in H4-APP cells and brain tissue of naive mice. EDTA (10 mm), BAPTA (10 μm), and RNAi silencing of IP3 receptor, NMDA receptor, or SERCA1 attenuated capase-3 activation. Memantine (4 μm) inhibited isoflurane-induced elevations in cytosolic calcium levels and attenuated isoflurane-induced caspase-3 activation, apoptosis, and cell viability. Memantine (20 mg/kg, i.p.) reduced isoflurane-induced caspase-3 activation in brain tissue of naive mice. These results suggest that disruption of calcium homeostasis underlies isoflurane-induced caspase activation and apoptosis. We also show for the first time that the NMDA receptor partial antagonist, memantine, can prevent isoflurane-induced caspase-3 activation and apoptosis in vivo and in vitro. These findings, indicating that isoflurane-induced caspase activation and apoptosis are dependent on cytosolic calcium levels, should facilitate the provision of safer anesthesia care, especially for Alzheimer's disease and elderly patients. PMID:18434534

  20. The Effects of Isoflurane and Desflurane on Cognitive Function in Humans

    PubMed Central

    Zhang, Bin; Tian, Ming; Zhen, Yu; Yue, Yun; Sherman, Janet; Zheng, Hui; Li, Shuren; Tanzi, Rudolph E.; Marcantonio, Edward R.; Xie, Zhongcong

    2014-01-01

    BACKGROUND: The etiology of postoperative cognitive decline (POCD) remains to be determined. Anesthetic isoflurane, but not desflurane, may induce neurotoxicity. However, the functional consequences of these effects have not been assessed. We therefore performed a pilot study to determine the effects of isoflurane and desflurane on cognitive function in humans. METHODS: The subjects included patients who had lower extremity or abdominal surgery under spinal anesthesia alone (S, n = 15), spinal plus desflurane anesthesia (SD, n = 15), or spinal plus isoflurane anesthesia (SI, n = 15) by randomization. Each of the subjects received cognitive tests immediately before and 1 week after anesthesia and surgery administered by an investigator who was blinded to the anesthesia regimen. POCD was defined using the scores from each of these tests. RESULTS: We studied 45 subjects, 24 males and 21 females. The mean age of the subjects was 69.0 ± 1.9 years. There was no significant difference in age and other characteristics among the treatment arms. The mean number of cognitive function declines in the S, SD, and SI groups was 1.13, 1.07, and 1.40, respectively. POCD incidence after SI (27%), but not SD (0%), anesthesia was higher than that after S (0%), P = 0.028 (3-way comparison). CONCLUSION: These findings from our pilot study suggest that isoflurane and desflurane may have different effects on postoperative cognitive function, and additional studies with a larger sample size and longer times of follow-up testing are needed. PMID:22075020

  1. Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling

    PubMed Central

    Baumgart, Joel P.; Zhou, Zhen-Yu; Hara, Masato; Cook, Daniel C.; Hoppa, Michael B.; Ryan, Timothy A.; Hemmings, Hugh C.

    2015-01-01

    Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in Ca2+ entry led to an equivalent reduction in exocytosis. These data thus indicate that anesthetic inhibition of neurotransmitter release from small SVs occurs primarily through reduced axon terminal Ca2+ entry without significant direct effects on Ca2+-exocytosis coupling or on the SV fusion machinery. Isoflurane inhibition of exocytosis and Ca2+ influx was greater in glutamatergic compared with GABAergic nerve terminals, consistent with selective inhibition of excitatory synaptic transmission. Such alteration in the balance of excitatory to inhibitory transmission could mediate reduced neuronal interactions and network-selective effects observed in the anesthetized central nervous system. PMID:26351670

  2. Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling.

    PubMed

    Baumgart, Joel P; Zhou, Zhen-Yu; Hara, Masato; Cook, Daniel C; Hoppa, Michael B; Ryan, Timothy A; Hemmings, Hugh C

    2015-09-22

    Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca(2+) influx without significantly altering the Ca(2+) sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca(2+)]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca(2+) ([Ca(2+)]e). Lowering external Ca(2+) to match the isoflurane-induced reduction in Ca(2+) entry led to an equivalent reduction in exocytosis. These data thus indicate that anesthetic inhibition of neurotransmitter release from small SVs occurs primarily through reduced axon terminal Ca(2+) entry without significant direct effects on Ca(2+)-exocytosis coupling or on the SV fusion machinery. Isoflurane inhibition of exocytosis and Ca(2+) influx was greater in glutamatergic compared with GABAergic nerve terminals, consistent with selective inhibition of excitatory synaptic transmission. Such alteration in the balance of excitatory to inhibitory transmission could mediate reduced neuronal interactions and network-selective effects observed in the anesthetized central nervous system. PMID:26351670

  3. Comparison of Dexmedetomidine-Ketamine with Isoflurane for Anesthesia of Chinchillas (Chinchilla lanigera).

    PubMed

    Fox, Lana; Snyder, Lindsey Bc; Mans, Christoph

    2016-01-01

    The objective of this study was to compare isoflurane with a combination of dexmedetomidine and ketamine, administered intramuscularly, for anesthesia in chinchillas (Chinchilla lanigera). In a prospective, complete crossover study, adult chinchillas (n = 8; age, 2 to 5 y) were anesthetized with a combination of dexmedetomidine (0.015 mg/kg IM) and ketamine (4 mg/kg IM). Atipamezole (0.15 mg/kg) was injected subcutaneously 45 min after dexmedetomidine-ketamine administration. For comparison, anesthesia also was induced and maintained with isoflurane in 100% oxygen, delivered by facemask. Anesthetic and physiologic parameters were recorded during each anesthesia, including various reflexes, heart rate, respiratory rate, body temperature, and SpO2. Food intake, fecal output, and body weight were recorded daily for 6 d after each anesthetic trial. Induction time, heart rate, respiratory rate, and body temperature did not differ significantly between the 2 anesthetic protocols. Recovery times were shorter and SpO2 was higher in animals that received isoflurane delivered in 100% oxygen. Food intake and fecal output were reduced in the dexmedetomidine-ketamine group for as long as 3 d after anesthesia, whereas isoflurane had no signifcant effect on food intake or fecal output. Both anesthetic protocols provided effective anesthesia in chinchillas. However, when anesthetized with dexmedetomidine-ketamine, chinchillas received room air and became hypoxemic. Future studies are needed to evaluate the effect of oxygen supplementation on anesthetic recovery and on the recovery of food intake and fecal output in chinchillas. PMID:27177565

  4. Isoflurane Inhibits the Tetrodotoxin-resistant Voltagegated Sodium Channel Nav1.8

    PubMed Central

    Herold, Karl F.; Nau, Carla; Ouyang, Wei; Hemmings, Hugh C.

    2009-01-01

    Background Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant (TTX-r) compared to other isoforms. Nav1.8 is highly expressed in dorsal root ganglion neurons and is functionally linked to nociception, but the sensitivity of TTX-r isoforms to inhaled anesthetics is unclear. Methods The sensitivities of heterologously expressed rat TTX-r Nav1.8 and endogenous tetrodotoxin-sensitive (TTX-s) Nav to the prototypic inhaled anesthetic isoflurane were tested in mammalian ND7/23 cells using patch-clamp electrophysiology. Results From a holding potential of −70 mV, isoflurane (0.53±0.06 mM, ~1.8 MAC at 24°C) reduced normalized peak Na+ current (INa) of Nav1.8 to 0.55±0.03 and of endogenous TTX-s Nav to 0.56±0.06. Isoflurane minimally inhibited INa from a holding potential of −140 mV. Isoflurane did not affect voltage-dependence of activation, but significantly shifted voltage-dependence of steady-state inactivation by −6 mV for Nav1.8 and by −7 mV for TTX-s Nav. IC50 values for inhibition of peak INa were 0.67±0.06 mM for Nav1.8 and 0.66±0.09 mM for TTX-s Nav; significant inhibition occurred at clinically relevant concentrations as low as 0.58 MAC. Isoflurane produced use-dependent block of Nav1.8; at a stimulation frequency of 10 Hz, 0.56±0.08 mM isoflurane reduced INa to 0.64±0.01 vs. 0.78±0.01 for control. Conclusion Isoflurane inhibited the tetrodotoxin-resistant isoform Nav1.8 with potency comparable to that for endogenous tetrodotoxin-sensitive Nav isoforms, indicating that sensitivity to inhaled anesthetics is conserved across diverse Nav family members. Block of Nav1.8 in dorsal root ganglion neurons could contribute to the effects of inhaled anesthetics on peripheral nociceptive mechanisms. PMID:19672182

  5. Distribution of cerebral blood flow during halothane versus isoflurane anesthesia in rats

    SciTech Connect

    Hansen, T.D.; Warner, D.S.; Todd, M.M.; Vust, L.J.; Trawick, D.C.

    1988-09-01

    The effects of halothane versus isoflurane on distribution of cerebral blood flow (CBF) were compared using 14C-iodoantipyrine autoradiography. Sprague-Dawley rats were exposed to 1 MAC of either halothane (n = 8) or isoflurane (n = 7) in 33% O2/balance nitrogen for 55 min prior to determination of CBF. Normoxia, normothermia, and normocapnia were maintained throughout the experiment and arterial pressures (MAP) were held within the range of 90-100 mmHg by infusion of blood. Coronal autoradiographic brain images were then digitized and optical density values converted to CBF with the use of 14C autoradiographic standards and arterial radioactivity data. Hemispheric, neocortical, subcortical, and selected local anatomical regions were defined on a cathode ray screen display by cursor outline. Mean CBF for each region was determined at each of eight standardized coronal brain sections, and area weighted average values for the whole brain were also calculated. Hemispheric CBF was identical in the two anesthetic groups: halothane = 150 +/- 16 ml.100 gm-1.min-1; isoflurane = 147 +/- 19 ml.100 gm-1.min-1. However, neocortical CBF was greater in halothane anesthetized animals (halothane = 185 +/- 16 ml.100 gm-1.min-1; isoflurane = 154 +/- 19 ml.100 gm-1.min-1, P = .004). The authors conclude that halothane and isoflurane exert regionally selective effects on CBF with halothane appearing to have a more pronounced effect on the neocortex. Previously reported discrepancies concerning the relative effects of these two agents on CBF may be due to inherent differences in the tissue regions measured by the different techniques.

  6. Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO2 chemosensitivity

    PubMed Central

    Iceman, Kimberly E.; Johansen, Sara L.; Wu, Yuanming; Harris, Michael B.; Richerson, George B.

    2015-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) neurons from the mouse and rat rostral medulla are stimulated by increased CO2 when studied in culture or brain slices. However, the response of 5-HT neurons has been variable when animals are exposed to hypercapnia in vivo. Here we examined whether halogenated inhalational anesthetics, which activate TWIK-related acid-sensitive K+ (TASK) channels, could mask an effect of CO2 on 5-HT neurons. During in vivo plethysmography in mice, isoflurane (1%) markedly reduced the hypercapnic ventilatory response (HCVR) by 78–96% depending upon mouse strain and ambient temperature. In a perfused rat brain stem preparation, isoflurane (1%) reduced or silenced spontaneous firing of medullary 5-HT neurons in situ and abolished their responses to elevated perfusate Pco2. In dissociated cell cultures, isoflurane (1%) hyperpolarized 5-HT neurons by 6.52 ± 3.94 mV and inhibited spontaneous firing. A subsequent decrease in pH from 7.4 to 7.2 depolarized neurons by 4.07 ± 2.10 mV, but that was insufficient to reach threshold for firing. Depolarizing current restored baseline firing and the firing frequency response to acidosis, indicating that isoflurane did not block the underlying mechanisms mediating chemosensitivity. These results demonstrate that isoflurane masks 5-HT neuron chemosensitivity in vitro and in situ and markedly decreases the HCVR in vivo. The use of this class of anesthetic has a particularly potent inhibitory effect on chemosensitivity of 5-HT neurons. PMID:25695656

  7. Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex

    PubMed Central

    Raz, Aeyal; Grady, Sean M.; Krause, Bryan M.; Uhlrich, Daniel J.; Manning, Karen A.; Banks, Matthew I.

    2014-01-01

    The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up “core” thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of

  8. Comparison of Surgical Conditions During Propofol or Isoflurane Anesthesia for Endoscopic Sinus Surgery

    PubMed Central

    Marzban, Shideh; Haddadi, Soudabeh; Mahmoudi Nia, Hossein; Heidarzadeh, Abtin; Nemati, Shadman; Naderi Nabi, Bahram

    2013-01-01

    Background The Anesthesia planning is an important and determining factor in the amount of intraoperative hemorrhage, which can affect the rate of intraoperative and postoperative complications. Objectives In this study we used two different anesthesia techniques in functional endoscopic sinus surgery (FESS) and compared the amount of hemorrhage in the two groups. Patients and Methods In a single–blind clinical trial, 44 patients with ASA class I and II candidate for FESS in Amir-Al-Momenin hospital in Rasht were entered the study and divided into two equal groups randomly. In both groups anesthesia was induced with propofol, remifentanil and cis. atracurium and then, infusion of propofol – remifentanil in the first group and isoflurane plus Remifentanil infusion in the second group was used for maintenance of anesthesia. Systolic blood pressure was maintained about 90 mmHg. Then on the basis of maximum allowable blood loss (MABL) formula, we calculated the percentage of hemorrhage. Finally the patients' hemorrhage was categorized into three groups (< 10%, 10-20%, > 20%). The surgeon's satisfaction from surgical field was calculated according to the Visual Analogue Scale. Then the data was statistically analyzed with T- test. Results There were meaningful differences between average of hemorrhage (propofol group = 155cc, and Isoflurane group = 291.3cc; P = 0.003), and surgeon’s satisfaction (propofol group = 1.9 and Isoflurane group = 2.95; P = 0.007). Conclusions The amount of hemorrhage in propofol group was less than Isoflurane group and the field condition was better in propofol group than the Isoflurane group. PMID:24282774

  9. Effects of isoflurane on somatosensory-evoked potentials in calves: A pilot study

    PubMed Central

    Truchetti, Geoffrey; Burns, Patrick; Nichols, Sylvain; Parent, Joane

    2015-01-01

    Somatosensory evoked potentials (SSEP) are used to monitor sensory function and are often recorded under general anesthesia. The objective of the study was to evaluate the effects of isoflurane on SSEPs in calves as it has not been reported. Eight calves (mean age: 40 days), were included in the study. Calves were anesthetized with a randomized sequence of four different isoflurane partial pressures. Blood gas analysis was performed before each measurement. SSEP were induced by repeated stimulation of the common dorsal digital nerve III. SSEPs were recorded from the lumbo-sacral junction (s-SSEP) and the head (c-SSEP). Latency and inter-amplitude of each peak were measured. For s-SSEP: One negative (Nsp1) and two positive (Psp1 and Psp2) peaks were identified in all tracings except for two calves. There was a significant effect of isoflurane on the latency of Psp2 (P = 0.01). Inter-amplitude decreased significantly with PaO2, PaCO2 and temperature (P < 0.05). Psp2 latency decreased with PaO2 (P = 0.01). For c-SSEP: two positive (Pc1 and Pc2) and two negative (Nc1 and Nc2) peaks were identified. There were identifiable peaks for the analysis of Pc1 latencies only. There was a significant positive linear relation between end-tidal isoflurane partial pressure (ETiso) and Pc1 latency (P = 0.04). None of the co-variables had a significant effect on the latency of Pc1 (P > 0.1). Isoflurane has a major impact on the recording of c-SSEP. Recording should be done at the lowest ETiso as possible, and anesthesia parameters should be kept constant. PMID:25673905

  10. Human Alveolar Echinococcosis in Kyrgyzstan

    PubMed Central

    Usubalieva, Jumagul; Minbaeva, Gulnara; Ziadinov, Iskender; Deplazes, Peter

    2013-01-01

    Human echinococcosis is a reportable disease in Kyrgyzstan. Between 1995 and 2011, human alveolar echinococcosis increased from <3 cases per year to >60 cases per year. The origins of this epidemic, which started in 2004, may be linked to the socioeconomic changes that followed the dissolution of the former Soviet Union. PMID:23763935

  11. The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

    SciTech Connect

    Wang Qiujun; Liang Ge; Yang Hui; Wang Shouping; Eckenhoff, Maryellen F.; Wei Huafeng

    2011-02-01

    Isoflurane is known to increase {beta}-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdh{sup Q111/Q111}) and wild type (STHdh{sup Q7/Q7}) striatal neurons. The primary cultured neurons were exposed for 24 h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP{sub 3}) receptor antagonist. Aggregation of huntingtin protein, cell viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdh{sup Q111/Q111} cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdh{sup Q111/Q111} huntingtin cells than in the wild type STHdh{sup Q7/Q7} striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdh{sup Q111/Q111} cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP{sub 3} receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdh{sup Q111/Q111} striatal cells.

  12. Isoflurane-sensitive presynaptic R-type calcium channels contribute to inhibitory synaptic transmission in the rat thalamus

    PubMed Central

    Joksovic, Pavle M.; Weiergräber, Marco; Lee, WooYong; Struck, Henrik; Schneider, Toni; Todorovic, Slobodan M.

    2009-01-01

    Since inhibitory synaptic transmission is a major mechanism of general anesthesia, we examined the effects of isoflurane on properties of GABAergic inhibitory currents in the reticular thalamic nucleus (nRT) in brain slices. The evoked inhibitory postsynaptic currents (eIPSCs) and spontaneous miniature synaptic currents (mIPSCs) of visualized nRT cells in young and adult rats were recorded. Consistent with postsynaptic effects on GABAA receptors, isoflurane prolonged the decay-time constants of both eIPSCs and mIPCSs. Surprisingly, isoflurane completely inhibited the amplitude of eIPSCs at clinically relevant concentrations (IC50 of 240 ± 20 μM), increased the paired-pulse ratio, and decreased the frequency of mIPSCs, indicating that presynaptic mechanisms may also contribute to the effects of isoflurane on IPSCs. The overall effect of isoflurane on eIPSCs in nRT cells was a decrease of net charge-transfer across the postsynaptic membrane. The application of 100 μM nickel (Ni2+) and the more specific R-type Ca2+ channel blocker SNX-482 (0.5 μM) decreased eIPSC amplitudes, increased the paired-pulse ratio, and attenuated isoflurane-induced inhibition of eIPSCs. In addition, isoflurane potently blocked currents in recombinant human CaV2.3 (α1E) channels with an IC50 of 206 ± 22 μM. Importantly, in vivo electroencephalographic (EEG) recordings in adult CaV2.3 knockout mice demonstrated alterations in isoflurane-induced burst-suppression activity. Because the thalamus has a key function in processing sensory information, sleep, and cognition, modulation of its GABAergic tone by presynaptic R-type Ca2+ channels may contribute to the clinical effects of general anesthesia. PMID:19193890

  13. Dexmedetomidine attenuates isoflurane-induced cognitive impairment through antioxidant, anti-inflammatory and anti-apoptosis in aging rat

    PubMed Central

    Wang, Xiaoning; Zhao, Binjiang; Li, Xue

    2015-01-01

    As a kind of α2 adrenergic receptor agonists, dexmedetomidine generates sedation, anti-anxiety and anesthesia effects by hyperpolarizing noradrenergic nerve cells in locus coeruleus. This study was designed to investigate the neuroprotective of dexmedetomidine attenuates isoflurane-induced cognitive impairment, and the possible underlying mechanism in aging rat. Firstly, we used isoflurane-induced aging rat model to analyze the therapeutical effect of dexmedetomidine on cognitive impairment. Next, commercial ELISA kits were used to analyze tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) and caspase-3 levels. In addition, Western blotting was used to detect the protein expression of P38 MAPK, PTEN and phosphorylation-Akt (p-Akt) expression. Our results showed that the neuroprotective of dexmedetomidine significantly attenuates isoflurane-induced cognitive impairment in aging rat. Moreover, dexmedetomidine significantly inhibited these TNF-α, IL-1β, MDA, SOD and caspase-3 activities in isoflurane-induced aging rat. Meanwhile, the neuroprotective effects of dexmedetomidine on isoflurane-induced cognitive impairment significantly suppressed Bcl-xL/Bad rate, P38 MAPK and PTEN protein expression and activated p-Akt protein expression in aging rat. Collectively, neuroprotective effect of dexmedetomidine attenuates isoflurane-induced cognitive impairment through antioxidant, anti-inflammatory and anti-apoptosis in aging rat. PMID:26770320

  14. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala

    PubMed Central

    Long II, Robert P.; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M.; Pidoplichko, Volodymyr I.; Figueiredo, Taiza H.; Braga, Maria F. M.

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting—but not permanent—impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning. PMID:27313904

  15. Isoflurane compared with fentanyl-midazolam-based anesthesia in patients undergoing heart transplantation: A retrospective cohort study.

    PubMed

    Hsu, Che-Hao; Hsu, Yung-Chi; Huang, Go-Shine; Lu, Chih-Cherng; Ho, Shung-Tai; Liaw, Wen-Jinn; Tsai, Yi-Ting; Lin, Chih-Yuan; Tsai, Chien-Sung; Lin, Tso-Chou

    2016-08-01

    Inhalation anesthetics provide myocardial protection for cardiac surgery. This study was undertaken to compare the perioperative effects between isoflurane and fentanyl-midazolam-based anesthesia for heart transplantation. A retrospective cohort study was conducted by reviewing the medical records of heart transplantation in a single medical center from 1990 to 2013. Patients receiving isoflurane or fentanyl-midazolam-based anesthesia were included. Those with preoperative severe pulmonary, hepatic, or renal comorbidities were excluded. The perioperative variables and postoperative short-term outcomes were analyzed, including blood glucose levels, urine output, inotropic use, time to extubation, and length of stay in the intensive care units. After reviewing 112 heart transplantations, 18 recipients with fentanyl-midazolam-based anesthesia, and 29 receiving isoflurane anesthesia with minimal low-flow technique were analyzed. After cessation of cardiopulmonary bypass, recipients with isoflurane anesthesia had a significantly lower mean level and a less increase of blood glucose, as compared with those receiving fentanyl-based anesthesia. In addition, there was less use of dobutamine upon arriving the intensive care unit and a shorter time to extubation after isoflurane anesthesia. Compared with fentanyl-midazolam-based anesthesia, isoflurane minimal low-flow anesthesia maintained better perioperative homeostasis of blood glucose levels, less postoperative use of inotropics, and early extubation time among heart-transplant recipients without severe comorbidities. PMID:27583900

  16. Postoperative catecholamine response to onychectomy in isoflurane-anesthetized cats. Effects of analgesics.

    PubMed

    Benson, G J; Wheaton, L G; Thurmon, J C; Tranquilli, W J; Olson, W A; Davis, C A

    1991-01-01

    Twenty-four healthy adult cats were anesthetized with isoflurane in oxygen. Six cats (group 1) served as controls; onychectomy of the forefeet was performed in the other three groups. Saline was administered intravenously to group 1, and morphine, xylazine, and salicylate were administered to groups 2, 3, and 4, respectively. Mixed venous blood samples were drawn for catecholamine analysis before induction of anesthesia, after recovery from anesthesia, and 30 minutes and 60 minutes after administration of the analgesic agent. Plasma catecholamine concentrations were determined by high performance liquid chromatography. Isoflurane anesthesia alone induced a transient increase in epinephrine concentration. Norepinephrine and epinephrine concentrations increased significantly after onychectomy. Morphine and xylazine significantly decreased postoperative norepinephrine and epinephrine concentrations; salicylate did not. PMID:1853554

  17. Brief Isoflurane Anesthesia Produces Prominent Phosphoproteomic Changes in the Adult Mouse Hippocampus.

    PubMed

    Kohtala, Samuel; Theilmann, Wiebke; Suomi, Tomi; Wigren, Henna-Kaisa; Porkka-Heiskanen, Tarja; Elo, Laura L; Rokka, Anne; Rantamäki, Tomi

    2016-06-15

    Anesthetics are widely used in medical practice and experimental research, yet the neurobiological basis governing their effects remains obscure. We have here used quantitative phosphoproteomics to investigate the protein phosphorylation changes produced by a 30 min isoflurane anesthesia in the adult mouse hippocampus. Altogether 318 phosphorylation alterations in total of 237 proteins between sham and isoflurane anesthesia were identified. Many of the hit proteins represent primary pharmacological targets of anesthetics. However, findings also enlighten the role of several other proteins-implicated in various biological processes including neuronal excitability, brain energy homeostasis, synaptic plasticity and transmission, and microtubule function-as putative (secondary) targets of anesthetics. In particular, isoflurane increases glycogen synthase kinase-3β (GSK3β) phosphorylation at the inhibitory Ser(9) residue and regulates the phosphorylation of multiple proteins downstream and upstream of this promiscuous kinase that regulate diverse biological functions. Along with confirmatory Western blot data for GSK3β and p44/42-MAPK (mitogen-activated protein kinase; reduced phosphorylation of the activation loop), we observed increased phosphorylation of microtubule-associated protein 2 (MAP2) on residues (Thr(1620,1623)) that have been shown to render its dissociation from microtubules and alterations in microtubule stability. We further demonstrate that diverse anesthetics (sevoflurane, urethane, ketamine) produce essentially similar phosphorylation changes on GSK3β, p44/p42-MAPK, and MAP2 as observed with isoflurane. Altogether our study demonstrates the potential of quantitative phosphoproteomics to study the mechanisms of anesthetics (and other drugs) in the mammalian brain and reveals how already a relatively brief anesthesia produces pronounced phosphorylation changes in multiple proteins in the central nervous system. PMID:27074656

  18. Management of Super-Refractory Status Epilepticus with Isoflurane and Hypothermia

    PubMed Central

    Zhumadilov, Agzam; Gilman, Charles P.; Viderman, Dmitriy

    2015-01-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus that continues 24 h or more after the onset of anesthesia, and includes those cases in which epilepsy is recurrent upon treatment reduction. We describe the presentation and successful management of a male patient with SRSE using the inhaled anesthetic isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed. PMID:25674075

  19. Isoflurane enhances both fast and slow synaptic inhibition in the hippocampus at amnestic concentrations

    PubMed Central

    Dai, Shuiping; Perouansky, Misha; Pearce, Robert A.

    2012-01-01

    Background Inhibition mediated by γ-aminobutyric acid type A (GABAA) receptors has long been considered an important target for a variety of general anesthetics. In the hippocampus, two types of phasic GABAA receptor-mediated inhibition coexist: GABAA,fast, which is expressed primarily at peri-somatic sites, and GABAA,slow, which is expressed primarily in the dendrites. Their spatial segregation suggests distinct functions: GABAA,slow may control plasticity of dendritic synapses, while GABAA,fast controls action potential initiation at the soma. We examined modulation of GABAA,fast and GABAA,slow inhibition by isoflurane at amnesic concentrations, and compared it to modulation by behaviorally equivalent doses of the GABAA receptor-selective drug etomidate. Methods Whole-cell recordings were conducted at near-physiological temperature from pyramidal cells in organotypic hippocampal cultures obtained from C57BL/6 x 129/SvJ F1 hybrid mice. GABAA receptor-mediated currents were isolated using glutamate receptor antagonists. GABAA,slow currents were evoked by electrical stimulation in the stratum lacunosum-moleculare. Miniature GABAA,fast currents were recorded in the presence of tetrodotoxin. Results 100 µM isoflurane (approximately EC50,amnesia) slowed fast and slow inhibitory postsynaptic current decay by approximately 25%. Higher concentrations, up to 400 µM, produced proportionally greater effects without altering current amplitudes. The effects on GABAA,slow were approximately one-half those produced by equi-amnesic concentrations of etomidate. Conclusions Isoflurane enhances both types of phasic GABAA receptor-mediated inhibition to similar degrees at amnesic concentrations. This pattern differs from etomidate, which at low concentrations selectively enhances slow inhibition. These effects of isoflurane are sufficiently large that they may contribute substantially to its suppression of hippocampal learning and memory. PMID:22343472

  20. Treatment of life-threatening hypercapnia with isoflurane in an infant with status asthmaticus.

    PubMed

    Masuda, Yoshiki; Tatsumi, Hiroomi; Goto, Kyoko; Imaizumi, Hitoshi; Yoshida, Shin-ichiro; Kimijima, Tomohiko; Yamakage, Michiaki

    2014-08-01

    We encountered a 2-year-old child with life-threatening hypercapnia, with a PaCO(2) of 238 mm Hg and severe respiratory and metabolic acidosis, due to status asthmaticus that was refractory to steroid and bronchodilator therapy. Suspecting ventilatory failure and excessive ventilation-induced obstructive shock, we started respiratory physiotherapy in synchrony with her respiration, to facilitate exhalation from her over-inflated lungs. Isoflurane inhalation was commenced in preparation for extracorporeal circulation, to reduce the hypercapnia. The combination of respiratory physiotherapy and isoflurane inhalation resulted in a rapid decrease in ventilatory resistance and PaCO(2) levels within a few minutes, with recovery of consciousness within 60 min. Isoflurane inhalation was gradually discontinued and steroid and aminophylline therapy were commenced. The patient recovered completely without any recurrence of her bronchospasm and without any residual neurological deficits. In our patient with a severe asthmatic attack, decreased exhalation secondary to asthma and overventilation during artificial ventilation resulted in overinflation of the lungs, which in turn led to cerebral edema and obstructive cardiac failure. The favorable outcome in this case was due to the short duration of hypercapnia. Hence, we conclude that the duration of hypercapnia is an important determinant of the morbidity and mortality of status asthmaticus-induced severe hypercapnia. PMID:24310852

  1. Isoflurane-Induced Changes in Righting Response and Breathing are Modulated by RGS Proteins

    PubMed Central

    Icaza, Eduardo E.; Huang, Xinyan; Fu, Ying; Neubig, Richard R.; Baghdoyan, Helen A.; Lydic, Ralph

    2011-01-01

    Background Recent evidence suggests that G protein coupled receptors, especially those linked to Gαi, contribute to the mechanisms of anesthetic action. Regulator of G protein signaling (RGS) proteins bind to activated Gαi and inhibit its signal transduction. Genomic knock-in mice with an RGS-insensitive Gαi2 G184S (Gαi2 GS) allele exhibit enhanced Gαi2 signaling and provide a novel approach for investigating the role of Gαi2 signaling and RGS proteins in general anesthesia. Methods Homozygous Gαi2 GS/GS and wild type (WT) mice were anesthetized with isoflurane and time (s) to loss and resumption of righting response was quantified. During recovery from isoflurane anesthesia breathing was quantified in a plethysmography chamber for both lines of mice. Results Gαi2 GS/GS mice required significantly less time for loss of righting and significantly more time for resumption of righting than WT mice. During recovery from isoflurane anesthesia, Gαi2 GS/GS mice exhibited significantly greater respiratory depression. Poincaré analyses show that GS/GS mice have diminished respiratory variability compared to WT mice. Conclusion Modulation of Gαi2 signaling by RGS proteins alters loss and resumption of wakefulness, and state-dependent changes in breathing. PMID:19843788

  2. Astaxanthin reduces isoflurane-induced neuroapoptosis via the PI3K/Akt pathway.

    PubMed

    Wang, Chun-Mei; Cai, Xiao-Lan; Wen, Qing-Ping

    2016-05-01

    Astaxanthin is an oxygen-containing derivative of carotenoids that effectively suppresses reactive oxygen and has nutritional and medicinal value. The mechanisms underlying the effects of astaxanthin on isoflurane‑induced neuroapoptosis remain to be fully understood. The present study was conducted to evaluate the protective effect of astaxanthin to reduce isoflurane‑induced neuroapoptosis and to investigate the underlying mechanisms. The results demonstrated that isoflurane induced brain damage, increased caspase‑3 activity and suppressed the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway in an in vivo model. However, treatment with astaxanthin significantly inhibited brain damage, suppressed caspase‑3 activity and upregulated the PI3K/Akt pathway in the isoflurane‑induced rats. Furthermore, isoflurane suppressed cell growth, induced cell apoptosis, enhanced caspase‑3 activity and downregulated the PI3K/Akt pathway in organotypic hippocampal slice culture. Administration of astaxanthin significantly promoted cell growth, reduced cell apoptosis and caspase‑3 activity, and upregulated the PI3K/Akt pathway and isoflurane‑induced neuroapoptosis. The present study demonstrated that downregulation of the PI3K/Akt pathway reduced the effect of astaxanthin to protect against isoflurane‑induced neuroapoptosis in the in vitro model. The results of the current study suggested that the protective effect of astaxanthin reduces the isoflurane-induced neuroapoptosis via activation of the PI3K/Akt signaling pathway. PMID:27035665

  3. Isoflurane Preconditioning Induces Neuroprotection by Up-Regulation of TREK1 in a Rat Model of Spinal Cord Ischemic Injury

    PubMed Central

    Wang, Kun; Kong, Xiangang

    2016-01-01

    This study aimed to explore the neuroprotection and mechanism of isoflurane on rats with spinal cord ischemic injury. Total 40 adult male Sprague-Dawley rats were divided into the four groups (n=10). Group A was sham-operation group; group B was ischemia group; group C was isoflurane preconditioning group; group D was isoflurane preconditioning followed by ischemia treatment group. Then the expressions of TWIK-related K+ channel 1 (TREK1) in the four groups were detected by immunofluorescent assay, real time-polymerase chain reactions (RT-PCR) and western blot. The primary neurons of rats were isolated and cultured under normal and hypoxic conditions. Besides, the neurons under two conditions were transfected with green fluorescent protein (GFP)-TREK1 and lentivirual to overexpress and silence TREK1. Additionally, the neurons were treated with isoflurane or not. Then caspase-3 activity and cell cycle of neurons under normal and hypoxic conditions were detected. Furthermore, nicotinamide adenine dinucleotide hydrate (NADH) was detected using NAD+/NADH quantification colorimetric kit. Results showed that the mRNA and protein expressions of TREK1 increased significantly in group C and D. In neurons, when TREK1 silenced, isoflurane treatment improved the caspase-3 activity. In hypoxic condition, the caspase-3 activity and sub-G1 cell percentage significantly increased, however, when TREK1 overexpressed the caspase-3 activity and sub-G1 cell percentage decreased significantly. Furthermore, both isoflurane treatment and overexpression of TREK1 significantly decreased NADH. In conclusion, isoflurane-induced neuroprotection in spinal cord ischemic injury may be associated with the up-regulation of TREK1. PMID:27469140

  4. The in vivo genotoxicity of cisplatin, isoflurane and halothane evaluated by alkaline comet assay in Swiss albino mice.

    PubMed

    Brozovic, Gordana; Orsolic, Nada; Knezevic, Fabijan; Horvat Knezevic, Anica; Benkovic, Vesna; Sakic, Katarina; Borojevic, Nikola; Dikic, Domagoj

    2011-08-01

    The aim of this study was to evaluate the genotoxicity of repeated exposure to isoflurane or halothane and compare it with the genotoxicity of repeated exposure to cisplatin. We also determined the genotoxicity of combined treatment with inhalation anaesthetics and cisplatin on peripheral blood leucocytes (PBL), brain, liver and kidney cells of mice. The mice were divided into six groups as follows: control, cisplatin, isoflurane, cisplatin-isoflurane, halothane and cisplatin-halothane, and were exposed respectively for three consecutive days. The mice were treated with cisplatin or exposed to inhalation anaesthetic; the combined groups were exposed to inhalation anaesthetic after treatment with cisplatin. The alkaline comet assay was performed. All drugs had a strong genotoxicity (P<0.05 vs. control group) in all of the observed cells. Isoflurane caused stronger DNA damage on the PBL and kidney cells, in contrast to halothane, which had stronger genotoxicity on brain and liver cells. The combination of cisplatin and isoflurane induced lower genotoxicity on PBL than isoflurane alone (P<0.05). Halothane had the strongest effect on brain cells, but in the combined treatment with cisplatin, the effect decreased to the level of cisplatin alone. Halothane also induced the strongest DNA damage of the liver cells, while the combination with cisplatin increased its genotoxicity even more. The genotoxicity of cisplatin and isoflurane on kidney cells were nearly at the same level, but halothane caused a significantly lower effect. The combinations of inhalation anaesthetics with cisplatin had stronger effects on kidney cells than inhalation anaesthetics alone. The observed drugs and their combinations induced strong genotoxicity on all of the mentioned cells. PMID:21509577

  5. Comparison of isoflurane and α-chloralose in an anesthetized swine model of acute pulmonary embolism producing right ventricular dysfunction.

    PubMed

    Beam, Daren M; Neto-Neves, Evandro M; Stubblefield, William B; Alves, Nathan J; Tune, Johnathan D; Kline, Jeffrey A

    2015-02-01

    Pulmonary embolism (PE) is a leading cause of sudden cardiac death, and a model is needed for testing potential treatments. In developing a model, we compared the hemodynamic effects of isoflurane and α-chloralose in an acute swine model of PE because the choice of anesthesia will likely affect the cardiovascular responses of an animal to PE. At baseline, swine that received α-chloralose (n = 6) had a lower heart rate and cardiac output and higher SpO2, end-tidal CO2, and mean arterial pressure than did those given isoflurane (n = 9). After PE induction, swine given α-chloralose compared with isoflurane exhibited a lower heart rate (63 ± 10 compared with 116 ± 15 bpm) and peripheral arterial pressure (52 ± 12 compared with 61 ± 12 mm Hg); higher SpO2 (98% ± 3% compared with 95% ± 1%), end-tidal CO2 (35 ± 4 compared with 32 ± 5), and systolic blood pressure (121 ± 8 compared with 104 ± 20 mm Hg); and equivalent right ventricular:left ventricular ratios (1.32 ± 0.50 compared with 1.23 ± 0.19) and troponin I mean values (0.09 ± 0.07 ng/mL compared with 0.09 ± 0.06 ng/mL). Isoflurane was associated with widely variable fibrinogen and activated partial thromboplastin time. Intraexperiment mortality was 0 of 6 animals for α-chloralose and 2 of 9 swine for isoflurane. All swine anesthetized with α-chloralose survived with sustained pulmonary hypertension, RV-dilation-associated cardiac injury without the confounding vasodilatory or coagulatory effects of isoflurane. These data demonstrate the physiologic advantages of α-chloralose over isoflurane for anesthesia in a swine model of severe submassive PE. PMID:25730758

  6. Swimming exercise ameliorates neurocognitive impairment induced by neonatal exposure to isoflurane and enhances hippocampal histone acetylation in mice.

    PubMed

    Zhong, T; Ren, F; Huang, C S; Zou, W Y; Yang, Y; Pan, Y D; Sun, B; Wang, E; Guo, Q L

    2016-03-01

    Isoflurane-induced neurocognitive impairment in the developing rodent brain is well documented, and regular physical exercise has been demonstrated to be a viable intervention for some types of neurocognitive impairment. This study was designed to investigate the potential protective effect of swimming exercise on both neurocognitive impairment caused by repeated neonatal exposure to isoflurane and the underlying molecular mechanism. Mice received 0.75% isoflurane exposures for 4h on postnatal days 7, 8, and 9. From the third month after anesthesia, the mice were subjected to regular swimming exercise for 4weeks, followed by a contextual fear condition (CFC) trial. We found that repeated neonatal exposure to isoflurane reduced freezing behavior during CFC testing and deregulated hippocampal histone H4K12 acetylation. Conversely, mice subjected to regular swimming exercise showed enhanced hippocampal H3K9, H4K5, and H4K12 acetylation levels, increased numbers of c-Fos-positive cells 1h after CFC training, and less isoflurane-induced memory impairment. We also observed increases in histone acetylation and of cAMP-response element-binding protein (CREB)-binding protein (CBP) during the swimming exercise program. The results suggest that neonatal isoflurane exposure-induced memory impairment was associated with dysregulation of H4K12 acetylation, which may lead to less hippocampal activation following learning tasks. Swimming exercise was associated with enhanced hippocampal histone acetylation and CBP expression. Exercise most likely ameliorated isoflurane-induced memory impairment by enhancing hippocampal histone acetylation and activating more neuron cells during memory formation. PMID:26748054

  7. [Pulmonary alveolar microlithiasis: Report of one case].

    PubMed

    Fernández F, Cristina; Salinas F, Mauricio; de Grazia K, José Andrés; Díaz P, Juan Carlos

    2014-05-01

    Pulmonary alveolar microlithiasis is an extremely rare disease characterized by intra-alveolar accumulation of calcified spherical particles (called microliths), due to a mutation of the gene encoding a membrane transport protein of the alveolar surface. Most patients are asymptomatic at diagnosis. The course of the disease is slowly progressive, with development of pulmonary fibrosis and respiratory failure. The "sandstorm" pattern is the characteristic finding of this disease. We report a 39-year-old female presenting with progressive dyspnea. A chest X ray showed ground-glass opacities and a high resolution CT scan showed numerous calcified lung micronodules. A surgical lung biopsy confirmed the diagnosis of pulmonary alveolar microlithiasis. PMID:25427025

  8. Clinicophysiological and haemodynamic effects of fentanyl with xylazine, medetomidine and dexmedetomidine in isoflurane-anaesthetised water buffaloes (Bubalus bubalis).

    PubMed

    Singh, Gyan D; Kinjavdekar, Prakash; Amarpal; Aithal, Hari P; Pawde, Abhijeet M; Zama, Malik M S; Singh, Jasmeet; Tiwary, Ramesh

    2013-01-01

    The present study was undertaken to investigate the sedative, analgesic and clinical effects of xylazine, medetomidine and dexmedetomidine with fentanyl as pre-anaesthetics in water buffaloes and to compare the dose-sparing effect of xylazine, medetomidine and dexmedetomidine on thiopental for induction and isoflurane for maintenance of anaesthesia in water buffaloes. Six male water buffaloes randomly received intravenous fentanyl (5.0 µg/kg body weight) and xylazine (0.05 mg/kg body weight), fentanyl (5.0 µg/kg body weight) and medetomidine (2.5 µg/kg body weight), fentanyl (5.0 µg/kg body weight) and dexmedetomidine (5.0 µg/kg body weight) at weekly intervals in groups I1, I2 and I3, respectively. After 15 min, the animals were restrained in right lateral recumbency and anaesthesia was induced by 5% thiopental sodium administered intravenously. The intubated animal was connected to the large animal anaesthesia machine and isoflurane in 100% oxygen (5 L/min) was insufflated for 60 min. The treatments were compared by clinicophysiological, haematobiochemical and haemodynamic parameters. Fentanyl-medetomidine and fentanyl-dexmedetomidine produced more cardiovascular depression during the pre-anaesthetic period but less depression of cardio-respiratory dynamics in the post induction and maintenance period. Quicker recovery was recorded in I2 and I3 groups. A lower dose of thiopental was required in group I3 (4.33 mg/kg ± 0.66 mg/kg) than in groups I2 (4.41 mg/kg ± 0.98 mg/kg) and I1 (4.83 mg/kg ± 0.79 mg/kg). The dose of isoflurane was less in group I3 (45.50 mL ± 5.45 mL) than in group I1 and I2 (48.66 mL ± 5.10 mL and 48.00 mL ± 6.38 mL). Better anaesthesia was recorded with fentanyl-dexmedetomidine-thiopental-isoflurane (group I3) than with fentanyl-medetomidine-thiopental-isoflurane (group I2) and fentanyl-xylazine-thiopental-isoflurane (group I1). Fentanyl-medetomidine and fentanyl-dexmedetomidine were better pre-anaesthetic agents in comparison to

  9. Effects of tail fat on recovery times of anesthesia with isoflurane in fat-tailed Iranian Lori-Bakhtiyari lambs

    PubMed Central

    Sharifi, Siavash; Raisi Sarteshnizi, Abbas; Sharifi, Farangis; Yousefian, Elham

    2015-01-01

    In the present study, the effect of tail fat on recovery times in intact sheep and sheep with a ligated median sacral artery following similar anesthetic exposure with isoflurane was investigated. This study was performed using seven healthy fat-tailed Iranian Lori-Bakhtiyari ewe lambs. The lambs were anesthetized twice at two week intervals (the experiment was performed in two stages). After mask induction with isoflurane in 100% oxygen, sheep were intubated and anesthesia was maintained for 4 hr using a rebreathing system. Induction and extubation times and time to sternal recumbency and attempts to stand were recorded during anesthetic induction and recovery (Stage 1). Two weeks later, prior to the second anesthesia, the median sacral artery (MSA) was ligated under epidural anesthesia in sheep. All sheep were anesthetized as mentioned above (Stage 2). No significant differences were observed for the induction time between two stages (p > 0.05) but extubation, sternal recumbency and attempts to stand times were significantly longer in intact sheep (Stage 1) after 4 hr anesthesia with isoflurane (p < 0.05). Recovery time was decreased following MSA ligation in fat-tailed sheep, which suggested that body fat had a major role in the recovery time of isoflurane in sheep. We developed an animal model to investigate fat drug solubility of isoflurane gas. Therefore, using less-soluble in fat anesthetics is better than high-soluble anesthetics for prolonged anesthesia to decrease postoperative complication in obese patient. PMID:26893809

  10. Effects of tail fat on recovery times of anesthesia with isoflurane in fat-tailed Iranian Lori-Bakhtiyari lambs.

    PubMed

    Sharifi, Siavash; Raisi Sarteshnizi, Abbas; Sharifi, Farangis; Yousefian, Elham

    2015-01-01

    In the present study, the effect of tail fat on recovery times in intact sheep and sheep with a ligated median sacral artery following similar anesthetic exposure with isoflurane was investigated. This study was performed using seven healthy fat-tailed Iranian Lori-Bakhtiyari ewe lambs. The lambs were anesthetized twice at two week intervals (the experiment was performed in two stages). After mask induction with isoflurane in 100% oxygen, sheep were intubated and anesthesia was maintained for 4 hr using a rebreathing system. Induction and extubation times and time to sternal recumbency and attempts to stand were recorded during anesthetic induction and recovery (Stage 1). Two weeks later, prior to the second anesthesia, the median sacral artery (MSA) was ligated under epidural anesthesia in sheep. All sheep were anesthetized as mentioned above (Stage 2). No significant differences were observed for the induction time between two stages (p > 0.05) but extubation, sternal recumbency and attempts to stand times were significantly longer in intact sheep (Stage 1) after 4 hr anesthesia with isoflurane (p < 0.05). Recovery time was decreased following MSA ligation in fat-tailed sheep, which suggested that body fat had a major role in the recovery time of isoflurane in sheep. We developed an animal model to investigate fat drug solubility of isoflurane gas. Therefore, using less-soluble in fat anesthetics is better than high-soluble anesthetics for prolonged anesthesia to decrease postoperative complication in obese patient. PMID:26893809

  11. Crystal structure of isoflurane bound to integrin LFA-1 supports a unified mechanism of volatile anesthetic action in the immune and central nervous systems

    SciTech Connect

    Zhang, Hongmin; Astrof, Nathan S.; Liu, Jin-Huan; Wang, Jia-huai; Shimaoka, Motomu

    2009-09-15

    Volatile anesthetics (VAs), such as isoflurane, induce a general anesthetic state by binding to specific targets (i.e., ion channels) in the central nervous system (CNS). Simultaneously, VAs modulate immune functions, possibly via direct interaction with alternative targets on leukocytes. One such target, the integrin lymphocyte function-associated antigen-1 (LFA-1), has been shown previously to be inhibited by isoflurane. A better understanding of the mechanism by which isoflurane alters protein function requires the detailed information about the drug-protein interaction at an atomic level. Here, we describe the crystal structure of the LFA-1 ligand-binding domain (I domain) in complex with isoflurane at 1.6 {angstrom}. We discovered that isoflurane binds to an allosteric cavity previously implicated as critical for the transition of LFA-1 from the low- to the high-affinity state. The isoflurane binding site in the I domain involves an array of amphiphilic interactions, thereby resembling a 'common anesthetic binding motif' previously predicted for authentic VA binding sites. These results suggest that the allosteric modulation of protein function by isoflurane, as demonstrated for the integrin LFA-1, might represent a unified mechanism shared by the interactions of volatile anesthetics with targets in the CNS. Crystal structure of isoflurane bound to integrin LFA-1 supports a unified mechanism of volatile anesthetic action in the immune and central nervous systems.

  12. Management of the alveolar cleft.

    PubMed

    Santiago, Pedro E; Schuster, Lindsay A; Levy-Bercowski, Daniel

    2014-04-01

    Orthopedic and orthodontic management of patients born with clefts of the lip, alveolus and palate is based on the application of basic biomechanical principles adapted to the individualized cleft anatomy. This article focuses on orthopedic and orthodontic preparation for 2 stages of interdisciplinary orthodontic/surgical cleft care: presurgical infant orthopedics (nasoalveolar molding) for lip/alveolus/nasal surgical repair and maxillary arch preparation for secondary alveolar bone grafting. These preparatory stages of orthopedic/orthodontic therapy are undertaken with the goal of restoring normal anatomic relationships to assist the surgeon in providing the best possible surgical care. PMID:24607190

  13. Self-tuning adaptive control of induced hypotension in humans: a comparison of isoflurane and sodium nitroprusside.

    PubMed

    Prys-Roberts, C; Millard, R K

    1990-07-01

    Induced hypotension is commonly used during surgery to decrease arterial pressure. Sodium nitroprusside and isoflurane are well-known hypotensive agents. The use of self-tuning adaptive control of induced hypotension was assessed with the use of sodium nitroprusside and isoflurane as hypotensive agents. Nineteen surgical patients were studied during closed-loop control of hypotension induced with sodium nitroprusside. This group of patients was compared with 10 similar patients in whom infusions of sodium nitroprusside were controlled manually by an anesthesiologist. Although the results of the two studies varied, no conclusion could be drawn regarding the superiority of either manual or closed-loop control. When manual versus automatic control of isoflurane-induced hypotension was assessed in a similar fashion, the two methods of induction were found to be comparable. PMID:2380754

  14. Evidence for the Use of Isoflurane as a Replacement for Chloral Hydrate Anesthesia in Experimental Stroke: An Ethical Issue

    PubMed Central

    Maud, Pétrault; Thavarak, Ouk; Cédrick, Lachaud; Michèle, Bastide; Vincent, Bérézowski; Olivier, Pétrault; Régis, Bordet

    2014-01-01

    Since an ethical issue has been raised regarding the use of the well-known anesthetic agent chloral hydrate, owing to its mutagenic and carcinogenic effects in animals, attention of neuroscientists has turned to finding out an alternative agent able to meet not only potency, safety, and analgesic efficacy, but also reduced neuroprotective effect for stroke research. The aim of this study was to compare the potential of chloral hydrate and isoflurane for both modulating the action of the experimental neuroprotectant MK801 and exerting analgesia. After middle cerebral artery occlusion in rats, no difference was observed in 24 h survival rate, success of ischemia, or infarct volume reduction between both anesthetics. However, isoflurane exerted a more pronounced analgesic effect than chloral hydrate as evidenced by formalin test 3 hours after anesthesia onset, thus encouraging the use of isoflurane in experimental stroke models. PMID:24719888

  15. Fluorescence anisotropy of diphenylhexatriene and its cationic Trimethylamino derivative in liquid dipalmitoylphosphatidylcholine liposomes: opposing responses to isoflurane

    PubMed Central

    2012-01-01

    Background The mechanism of action of volatile general anesthetics has not yet been resolved. In order to identify the effects of isoflurane on the membrane, we measured the steady-state anisotropy of two fluorescent probes that reside at different depths. Incorporation of anesthetic was confirmed by shifting of the main phase transition temperature. Results In liquid crystalline dipalmitoylphosphatidylcholine liposomes, isoflurane (7-25 mM in the bath) increases trimethylammonium-diphenylhexatriene fluorescence anisotropy by ~0.02 units and decreases diphenylhexatriene anisotropy by the same amount. Conclusions The anisotropy data suggest that isoflurane decreases non-axial dye mobility in the headgroup region, while increasing it in the tail region. We propose that these results reflect changes in the lateral pressure profile of the membrane. PMID:22444827

  16. Synthesis of Dipalmitoyl Lecithin by Alveolar Macrophages

    PubMed Central

    Mason, Robert J.; Huber, Gary; Vaughan, Martha

    1972-01-01

    A reliable, relatively simple method for isolation and quantification of disaturated lecithins is described. In rabbit lung, 34% of the lecithins were disaturated, in alveolar macrophages, 19%. More than 95% of the fatty acids of the disaturated lecithins from lung and alveolar macrophages was palmitic. Hence, the disaturated lecithins from these sources were essentially all dipalmitoyl lecithin. Both heterophils and alveolar macrophages incorporated 14C-labeled choline and palmitate into disaturated lecithins. Liver slices in which only about 1% of the lecithins were disaturated incorporated very little of these precursors into this fraction. Of the palmitate incorporated in vitro into disaturated lecithins by alveolar macrophages, heterophils, and lung slices, 37% was in the 1 position. In disaturated lecithins isolated from pulmonary lavage fluid, alveolar macrophages, and lung of rabbit 8-12 hr after a single intravenous injection of palmitic-1-14C acid, 45% of the 14C was in position 1. At earlier times, from 20-240 min after injection, the distribution of 14C was similar in the samples from lung, but in those from alveolar macrophages and lavage fluid, the percentage in position 1 was slightly lower. Glycerol-U-14C was incorporated into disaturated lecithins by alveolar macrophages and by lung slices in vitro. Both tissues incorporated very little label from ethanolamine or from methyl-labeled methionine into this fraction. All of the data are consistent with the view that alveolar macrophages synthesize dipalmitoyl lecithin via the cytidine diphosphate-choline pathway. PMID:5066597

  17. Diffuse Alveolar Hemorrhage Associated with Warfarin Therapy

    PubMed Central

    Kaya, Bülent; Yildiz, Ibrahim; Baha, Reshat Mehmet; Zeytun, Neslihan Ebru Eryaşar; Yetisgen, Azize

    2015-01-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to therapy of warfarin use. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin. PMID:26347781

  18. Pulse granuloma of the alveolar ridge.

    PubMed

    Mincer, H H; McCoy, J M; Turner, J E

    1979-08-01

    Six examples of pulse granulomas of the alveolar ridge are presented. The lesion consists of a foreign-body granuloma containing identifiable particles of leguminous foods. The vegetable matter is introduced through an alveolar defect, usually a postextraction socket. Simple curettage is apparently adequate treatment to effect cure. PMID:382018

  19. Diffuse alveolar hemorrhage following alemtuzumab.

    PubMed

    Sachdeva, Ashutosh; Matuschak, George M

    2008-06-01

    This study describes an unusual patient with X-linked Alport syndrome (XLAS) in whom diffuse alveolar hemorrhage (DAH) developed as a complication of alemtuzumab therapy following renal transplantation. A 26-year-old man with XLAS underwent retransplantation with a cadaveric renal allograft. He received alemtuzumab therapy as a part of an immunosuppressive induction protocol, and dyspnea and hemoptysis developed. A chest CT scan showed diffuse alveolar opacities. Bronchoscopy was performed to determine the cause of hemoptysis and hypoxia. BAL showed a characteristic increasingly bloody return in the sequential aliquots. There was no growth of pathogenic bacteria or evidence of opportunistic infection. Clinical improvement occurred with the initiation of steroids, and the patient required short-term mechanical ventilation for acute respiratory failure. To our knowledge, this is the first reported case of DAH associated with use of alemtuzumab therapy, although other pulmonary toxicities have been described. The prevalence of this form of pulmonary toxicity is unclear and requires further systematic study. PMID:18574290

  20. Control of intraoperative hypertension with isoflurane in patients with coronary artery disease: effects on regional myocardial blood flow and metabolism.

    PubMed

    Sahlman, L; Milocco, I; Appelgren, L; William-Olsson, G; Ricksten, S E

    1989-02-01

    The effect of isoflurane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anesthesia, to control intraoperative hypertension was investigated. Twenty-two patients with two- or three-vessel coronary artery disease with an ejection fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary hemodynamics, and regional (great cardiac vein, GCVF) myocardial blood flow and myocardial metabolic parameters were measured. In 10 patients, both GCVF and global (coronary sinus, CSF) myocardial blood flows were recorded. Measurements were made 1) after induction of anesthesia but prior to skin incision, 2) during sternotomy, and 3) during isoflurane administration after its use to reduce arterial pressure to the presternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance accompanied by increases in heart rate, pulmonary capillary wedge pressure, (PCWP) regional myocardial oxygen consumption and extraction, GCVF and total coronary vascular resistance. Isoflurane reduced systemic arterial pressure but not PCWP, to presternotomy levels within 6.9 +/- 0.7 minutes at an end-tidal concentration of 1.5 +/- 0.2%. Isoflurane induced a pronounced systemic and coronary vasodilatation and increases in cardiac index, heart rate and regional myocardial oxygen extraction while the GCVF/CSF ratio remained unchanged. While mean regional--MLE% values were not effected by sternotomy, in two patients myocardial lactate production was seen during sternotomy but not during isoflurane. In another two patients, isoflurane induced lactate production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2783640

  1. Dose-dependent effects of the clinical anesthetic isoflurane on Octopus vulgaris: a contribution to cephalopod welfare.

    PubMed

    Polese, Gianluca; Winlow, William; Di Cosmo, Anna

    2014-12-01

    Recent progress in animal welfare legislation relating to invertebrates has provoked interest in methods for the anesthesia of cephalopods, for which different approaches to anesthesia have been tried but in most cases without truly anesthetizing the animals. For example, several workers have used muscle relaxants or hypothermia as forms of "anesthesia." Several inhalational anesthetics are known to act in a dose-dependent manner on the great pond snail Lymnaea stagnalis, a pulmonate mollusk. Here we report, for the first time, on the effects of clinical doses of the well-known inhalational clinical anesthetic isoflurane on the behavioral responses of the common octopus Octopus vulgaris. In each experiment, isoflurane was equilibrated into a well-aerated seawater bath containing a single adult O. vulgaris. Using a web camera, we recorded each animal's response to touch stimuli eliciting withdrawal of the arms and siphon and observed changes in the respiratory rate and the chromatophore pattern over time (before, during, and after application of the anesthetic). We found that different animals of the same size responded with similar behavioral changes as the isoflurane concentration was gradually increased. After gradual application of 2% isoflurane for a maximum of 5 min (at which time all the responses indicated deep anesthesia), the animals recovered within 45-60 min in fresh aerated seawater. Based on previous findings in gastropods, we believe that the process of anesthesia induced by isoflurane is similar to that previously observed in Lymnaea. In this study we showed that isoflurane is a good, reversible anesthetic for O. vulgaris, and we developed a method for its use. PMID:25369208

  2. Prostate cancer cell malignancy via modulation of HIF-1α pathway with isoflurane and propofol alone and in combination

    PubMed Central

    Huang, H; Benzonana, L L; Zhao, H; Watts, H R; Perry, N J S; Bevan, C; Brown, R; Ma, D

    2014-01-01

    Background: Surgery is considered to be the first line treatment for solid tumours. Recently, retrospective studies reported that general anaesthesia was associated with worse long-term cancer-free survival when compared with regional anaesthesia. This has important clinical implications; however, the mechanisms underlying those observations remain unclear. We aim to investigate the effect of anaesthetics isoflurane and propofol on prostate cancer malignancy. Methods: Prostate cancer (PC3) cell line was exposed to commonly used anaesthetic isoflurane and propofol. Malignant potential was assessed through evaluation of expression level of hypoxia-inducible factor-1α (HIF-1α) and its downstream effectors, cell proliferation and migration as well as development of chemoresistance. Results: We demonstrated that isoflurane, at a clinically relevant concentration induced upregulation of HIF-1α and its downstream effectors in PC3 cell line. Consequently, cancer cell characteristics associated with malignancy were enhanced, with an increase of proliferation and migration, as well as development of chemoresistance. Inhibition of HIF-1α neosynthesis through upper pathway blocking by a PI-3K-Akt inhibitor or HIF-1α siRNA abolished isoflurane-induced effects. In contrast, the intravenous anaesthetic propofol inhibited HIF-1α activation induced by hypoxia or CoCl2. Propofol also prevented isoflurane-induced HIF-1α activation, and partially reduced cancer cell malignant activities. Conclusions: Our findings suggest that modulation of HIF-1α activity by anaesthetics may affect cancer recurrence following surgery. If our data were to be extrapolated to the clinical setting, isoflurane but not propofol should be avoided for use in cancer surgery. Further work involving in vivo models and clinical trials is urgently needed to determine the optimal anaesthetic regimen for cancer patients. PMID:25072260

  3. The effect of isoflurane anesthesia on the electroencephalogram assessed by harmonic wavelet bicoherence-based indices

    NASA Astrophysics Data System (ADS)

    Li, Duan; Li, Xiaoli; Hagihira, Satoshi; Sleigh, Jamie W.

    2011-10-01

    Bicoherence quantifies the degree of quadratic phase coupling among different frequency components within a signal. Previous studies, using Fourier-based methods of bicoherence calculation (FBIC), have demonstrated that electroencephalographic bicoherence can be related to the end-tidal concentration of inhaled anesthetic drugs. However, FBIC methods require excessively long sections of the encephalogram. This problem might be overcome by the use of wavelet-based methods. In this study, we compare FBIC and a recently developed wavelet bicoherence (WBIC) method as a tool to quantify the effect of isoflurane on the electroencephalogram. We analyzed a set of previously published electroencephalographic data, obtained from 29 patients who underwent elective abdominal surgery under isoflurane general anesthesia combined with epidural anesthesia. Nine potential indices of the electroencephalographic anesthetic effect were obtained from the WBIC and FBIC techniques. The relationship between each index and end-tidal concentrations of isoflurane was evaluated using correlation coefficients (r), the inter-individual variations (CV) of index values, the coefficient of determination (R2) of the PKPD models and the prediction probability (PK). The WBIC-based indices tracked anesthetic effects better than the traditional FBIC-based ones. The DiagBic_En index (derived from the Shannon entropy of the diagonal bicoherence values) performed best [r = 0.79 (0.66-0.92), CV = 0.08 (0.05-0.12), R2 = 0.80 (0.75-0.85), PK = 0.79 (0.75-0.83)]. Short data segments of ~10-30 s were sufficient to reliably calculate the indices of WBIC. The wavelet-based bicoherence has advantages over the traditional Fourier-based bicoherence in analyzing volatile anesthetic effects on the electroencephalogram.

  4. Labour time required for piglet castration with isoflurane-anaesthesia using shared and stationary inhaler devices.

    PubMed

    Weber, Sabrina; Das, Gürbüz; Waldmann, Karl-Heinz; Gauly, Matthias

    2014-01-01

    Isoflurane-anaesthesia combined with an analgesic represents a welfare-friendly method of pain mitigation for castration of piglets. However, it requires an inhaler device, which is uneconomic for small farms. Sharing a device among farms may be an economical option if the shared use does not increase labour time and the resulting costs. This study aimed to investigate the amount and components of labour time required for piglet castration with isoflurane anaesthesia performed with stationary and shared devices. Piglets (N = 1579) were anaesthetised with isoflurane (using either stationary or shared devices) and castrated.The stationary devices were used in a group (n = 5) of larger farms (84 sows/farm on an average), whereas smaller farms (n = 7; 32 sows/farm on an average) shared one device. Each farm was visited four times and labour time for each process-step was recorded. The complete process included machine set-up, anaesthesia and castration by a practitioner, and preparation, collection and transport of piglets by a farmer. Labour time of the complete process was increased (P = 0.012) on farms sharing a device (266 s/piglet) compared to farms using stationary devices (177 s/ piglet), due to increased time for preparation (P = 0.055), castration (P = 0.026) and packing (P = 0.010) when sharing a device. However, components of the time budget of farms using stationary or shared devices did not differ significantly (P > 0.05). Cost arising from time spent by farmers did not differ considerably between the use of stationary (0.28 Euro per piglet) and shared (0.26 Euro) devices. It is concluded that costs arising from the increased labour time due to sharing a device can be considered marginal, since the high expenses originating from purchasing an inhaler device are shared among several farms. PMID:24693654

  5. Chaos analysis of EEG during isoflurane-induced loss of righting in rats.

    PubMed

    MacIver, M B; Bland, Brian H

    2014-01-01

    It has long been known that electroencephalogram (EEG) signals generate chaotic strange attractors and the shape of these attractors correlate with depth of anesthesia. We applied chaos analysis to frontal cortical and hippocampal micro-EEG signals from implanted microelectrodes (layer 4 and CA1, respectively). Rats were taken to and from loss of righting reflex (LORR) with isoflurane and behavioral measures were compared to attractor shape. Resting EEG signals at LORR differed markedly from awake signals, more similar to slow wave sleep signals, and easily discerned in raw recordings (high amplitude slow waves), and in fast Fourier transform analysis (FFT; increased delta power), in good agreement with previous studies. EEG activation stimulated by turning rats on their side, to test righting, produced signals quite similar to awake resting state EEG signals. That is, the high amplitude slow wave activity changed to low amplitude fast activity that lasted for several seconds, before returning to slow wave activity. This occurred regardless of whether the rat was able to right itself, or not. Testing paw pinch and tail clamp responses produced similar EEG activations, even from deep anesthesia when burst suppression dominated the spontaneous EEG. Chaotic attractor shape was far better at discerning between these awake-like signals, at loss of responses, than was FFT analysis. Comparisons are provided between FFT and chaos analysis of EEG during awake walking, slow wave sleep, and isoflurane-induced effects at several depths of anesthesia. Attractors readily discriminated between natural sleep and isoflurane-induced "delta" activity. Chaotic attractor shapes changed gradually through the transition from awake to LORR, indicating that this was not an on/off like transition, but rather a point along a continuum of brain states. PMID:25360091

  6. Isoflurane reduces motile sperm counts in the Sprague-Dawley rat.

    PubMed

    Campion, Sarah N; Cappon, Gregg D; Chapin, Robert E; Jamon, Raul T; Winton, Timothy R; Nowland, William S

    2012-01-01

    Animal and care use practices are constantly evolving. These can have unexpected consequences on the data collected from such procedures. One example is the recent change in our animal facility, based on recommendations from the Newcastle Consensus Meeting on Carbon Dioxide Euthanasia of Laboratory Animals, from CO(2) to isoflurane for anesthesia. The current study was conducted to determine the effects of isoflurane on sperm motility, as compared to two different CO(2) euthanasia procedures. Sperm motility was evaluated after euthanasia by a standard 5-minute CO(2) euthanasia procedure, an extended 10-minute CO(2) euthanasia procedure, or by isoflurane anesthesia followed by exsanguination (iso/exsanguination). The 5-minute CO(2) procedure produced sperm motility of 94.3 ± 1.7% motile sperm with 65.6 ± 16.8 sperm/field. By comparison, iso/exsanguination reduced that count to 3.3 ± 2.3 sperm/field and only 60.7 ± 32.0% motile sperm. The reduction in sperm motility after iso/exsanguination appeared to have been due primarily to the reduction in the number of sperm expelled from the vas deferens (3.3), compared to that after 5-minute CO(2) (65.6). This reduction in number of sperm available for evaluation, in the presence of a constant level of background debris, which was counted by the computer optics system as nonmotile sperm, resulted in an apparent reduction in motility. Using the extended 10-minute CO(2) procedure produced sperm data in between the other two extremes: 77.6 ± 36.1% motile sperm with 34.6 ± 28.3 sperm/field. The results of this study support the hypothesis that isoflurane inhibits contraction of the smooth muscle of the vas deferens, resulting in a decreased number of expelled sperm. Given these findings, it is important that careful consideration be taken to select an appropriate anesthesia/euthanasia method. PMID:21774737

  7. Vertical Alveolar Ridge Augmentation by Distraction Osteogenesis

    PubMed Central

    Kumar, N. Nanda; Ravindran, C.

    2015-01-01

    Introduction Compromised alveolar ridge in vertical and horizontal dimension is a common finding in patients visiting practitioners for dental prosthesis. Various treatment modalities are available for correction of deficient ridges among which alveolar distraction osteogenesis is one. Aim To study the efficacy of alveolar distraction osteogenesis in augmentation of alveolar ridges deficient in vertical dimension. Materials and Methods Ten patients aged 16 to 46 years with deficient alveolar ridge underwent ridge augmentation in 11 alveolar segments using the distraction osteogenesis method. For each patient a custom made distraction device was fabricated. The device was indigenously manufactured with SS-316 (ISO 3506). Results The vertical bone gain reached more than 10mm without the use of bone transplantation. Certain complications like incorrect vector of distraction, paresthesia, pain and loss of transport segment were encountered during the course of the study. Conclusion Alveolar vertical distraction osteogenesis is a reliable and predictable technique for both hard and soft tissue genesis. Implant placement is feasible with primary stability in neogenerated bone at the level of the distracted areas. PMID:26816991

  8. Isoflurane waste anesthetic gas concentrations associated with the open-drop method.

    PubMed

    Taylor, Douglas K; Mook, Deborah M

    2009-01-01

    The open-drop technique is used frequently for anesthetic delivery to small rodents. Operator exposure to waste anesthetic gas (WAG) is a potential occupational hazard if this method is used without WAG scavenging. This study was conducted to determine whether administration of isoflurane by the open-drop technique without exposure controls generates significant WAG concentrations. We placed 0.1, 0.2, or 0.3 ml of liquid isoflurane into screw-top 500 or 1000 ml glass jars. WAG concentration was measured at the opening of the container and 20 and 40 cm from the opening, a distance at which users likely would operate, at 1, 2, or 3 min WAG was measured by using a portable infrared gas analyzer. Mean WAG concentrations at the vessel opening were as high as 662 +/- 168 ppm with a 500 ml jar and 122 +/- 87 ppm with a 1000 ml jar. At operator levels, WAG concentrations were always at or near 0 ppm. For measurements made at the vessel opening, time was the only factor that significantly affected WAG concentration when using the 500 ml jar. Neither time nor liquid volume were significant factors when using 1000 ml jar. At all liquid volumes and time points, the WAG concentration associated with using the 500 ml container was marginally to significantly greater than that for the 1000 ml jar. PMID:19245753

  9. The neurochemical profile of the hippocampus in isoflurane-treated and unanesthetized rat pups

    PubMed Central

    Akulov, Andrey E.

    2015-01-01

    In vivo study of cerebral metabolism in neonatal animals by high-resolution magnetic resonance spectroscopy (MRS) is an important tool for deciphering the developmental origins of adult diseases. Up to date, all in vivo spectrum acquisition procedures have been performed in neonatal rodents under anesthesia. However, it is still unknown if the inhaled anesthetic isoflurane, which is commonly used in magnetic resonance imaging studies, could affect metabolite levels in the brain of neonatal rats. Moreover, the unanesthetized MRS preparation that uses neonatal rodent pups is still lacking. Here, a novel restraint protocol was developed for neonatal rats in accordance with the European Directive 2010/63/EU. This protocol shares the same gradation of severity as the protocol for non-invasive magnetic resonance imaging of animals with appropriate sedation or anesthesia. Such immobilization of neonatal rats without anesthesia can be implemented for MRS studies when an interaction between anesthetic and target drugs is expected. Short-term isoflurane treatment did not affect the levels of key metabolites in the hippocampi of anesthetized pups and, in contrast to juvenile and adult rodents, it is suitable for MRS studies in neonatal rats when the interaction between anesthetic and target drugs is not expected. PMID:27486369

  10. Comparing the Effects of Isoflurane and Alpha Chloralose upon Mouse Physiology.

    PubMed

    Low, Lucie A; Bauer, Lucy C; Klaunberg, Brenda A

    2016-01-01

    Functional magnetic resonance imaging of mice requires that the physiology of the mouse (body temperature, respiration and heart rates, blood pH level) be maintained in order to prevent changes affecting the outcomes of functional scanning, namely blood oxygenation level dependent (BOLD) measures and cerebral blood flow (CBF). The anesthetic used to sedate mice for scanning can have major effects on physiology. While alpha chloralose has been commonly used for functional imaging of rats, its effects on physiology are not well characterized in the literature for any species. In this study, we anesthetized or sedated mice with isoflurane or alpha chloralose for up to two hours, and monitored physiological parameters and arterial blood gasses. We found that, when normal body temperature is maintained, breathing rates for both drugs decrease over the course of two hours. In addition, alpha chloralose causes a substantial drop in heart rate and blood pH with severe hypercapnia (elevated blood CO2) that is not seen in isoflurane-treated animals. We suggest that alpha chloralose does not maintain normal mouse physiology adequately for functional brain imaging outcome measures. PMID:27148970

  11. Adding Emulsified Isoflurane to Cardioplegia Solution Produces Cardiac Protection in a Dog Cardiopulmonary Bypass Model

    PubMed Central

    Huang, Han; Zhou, Cheng; Liu, Jin; Song, Haibo; Qiu, Yan

    2016-01-01

    This study investigated whether caridoplegia solution with Emulsified Isoflurane (EI) could improve cardiaoprotection in a dog CPB model of great similarity to clinical settings. Adult dogs were randomly assigned to receive one of the following cardioplegia solutions: St. Thomas with EI (group ST+EI), St. Thomas with 30% Intralipid (group ST+EL) and St. Thomas alone (group ST). The aorta was cross-clamped for two hours followed by reperfusion for another two hours, during which cardiac output was measured and dosages of positive inotropic agent to maintain normal hemodynamics were recorded. Serum level of cardiac troponin I (cTnI) and CK-MB were measured. Deletion of cardiac mitochondrial DNA was examined at the end of reperfusion. Compared with ST, ST+EI decreased the requirement of dopamine support while animals receiving ST+EI had a significantly larger cardiac output. ST+EI reduced post-CPB release of cTnI and CK-MB. Mitochondrial DNA loss was observed in only one of the tested animals from group ST+EI while it was seen in all the tested animals from group ST+EL and ST. Addition of emulsified isoflurane into cardioplegia solution protects against myocardial ischemia reperfusion injury. This protective effect might be mediated by preserving mitochondrial ultrastructure and DNA integrity. PMID:27121996

  12. Propofol Compared to Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

    SciTech Connect

    Kajimoto, Masaki; Atkinson, D. B.; Ledee, Dolena R.; Kayser, Ernst-Bernhard; Morgan, Phil G.; Sedensky, Margaret M.; Isern, Nancy G.; Des Rosiers, Christine; Portman, Michael A.

    2014-01-08

    Anesthetics used in infants and children are implicated in development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in an immature swine model anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon labeled glucose and leucine in the common carotid artery in order to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared-spectroscopy. Compared to isoflurane, propofol depleted ATP and glycogen stores. Propofol also decreased pools of the CAC intermediates, citrate and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked accumulation of lactate. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype which resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations which typically accompany propofol infusion syndrome. These metabolic abnormalities may play a role in neurotoxity observed with propofol in the vulnerable immature brain.

  13. Isoflurane and desflurane at clinically relevant concentrations induce amyloid {beta}-peptide oligomerization: An NMR study

    SciTech Connect

    Mandal, Pravat K Fodale, Vincenzo

    2009-02-13

    Current understanding on Alzheimer's disease (AD) reveals that soluble amyloid {beta}-peptide (A{beta}) oligomeric formation plays an important role in AD pathophysiology. A potential role for several inhaled anesthetics in promoting A{beta} oligomer formation has been suggested. Using a nuclear magnetic resonance (NMR) study, we previously demonstrated that at a high concentration (higher than clinically relevant concentrations), the inhaled anesthetics halothane and isoflurane, interact with specific amino acid residues (G29, A30, and I31) and induce A{beta} oligomerization. The present study confirms this is true at a clinically relevant concentration. Isoflurane and desflurane induce A{beta} oligomerization by inducing chemical shift changes of the critical amino acid residues (G29, A30, and I31), reinforcing the evidence that perturbation of these three crucial residues indeed plays an important role in oligomerization. These findings support the emerging hypothesis that several commonly used inhaled anesthetics could be involved in neurodegeneration, as well as risk factor for accelerating the onset of AD.

  14. Comparing the Effects of Isoflurane and Alpha Chloralose upon Mouse Physiology

    PubMed Central

    Bauer, Lucy C.; Klaunberg, Brenda A.

    2016-01-01

    Functional magnetic resonance imaging of mice requires that the physiology of the mouse (body temperature, respiration and heart rates, blood pH level) be maintained in order to prevent changes affecting the outcomes of functional scanning, namely blood oxygenation level dependent (BOLD) measures and cerebral blood flow (CBF). The anesthetic used to sedate mice for scanning can have major effects on physiology. While alpha chloralose has been commonly used for functional imaging of rats, its effects on physiology are not well characterized in the literature for any species. In this study, we anesthetized or sedated mice with isoflurane or alpha chloralose for up to two hours, and monitored physiological parameters and arterial blood gasses. We found that, when normal body temperature is maintained, breathing rates for both drugs decrease over the course of two hours. In addition, alpha chloralose causes a substantial drop in heart rate and blood pH with severe hypercapnia (elevated blood CO2) that is not seen in isoflurane-treated animals. We suggest that alpha chloralose does not maintain normal mouse physiology adequately for functional brain imaging outcome measures. PMID:27148970

  15. Occupational exposure to isoflurane during anaesthesia induction with standard and scavenging double masks in dogs, pigs and ponies.

    PubMed

    Säre, H; Ambrisko, T D; Moens, Y

    2011-07-01

    Induction of anaesthesia using a face mask may cause workplace pollution with anaesthetics. The aim of this study was to compare the effect of the use of a standard versus a scavenging double face mask on isoflurane pollution during induction of anaesthesia in experimental animals: six dogs, 12 pigs and five ponies. Pigs were anaesthetized only once using either mask type randomly (n = 6). Dogs and ponies were anaesthetized twice, using different mask types for each occasion in a random order with at least 14 days between experiments. The masks were attached to a Bain breathing system (dogs and pigs) or to a circle system (ponies) using a fresh gas flow of 300 or 50 mL/kg/min, respectively, with 5% vaporizer dial setting. Isoflurane concentrations were measured in the anaesthetist's breathing zone using an infrared photoacoustic spectrometer. The peak isoflurane concentrations (pollution) during baseline and induction periods were compared with Wilcoxon test in all species, and values between the mask types were compared with either Wilcoxon (ponies and dogs) or Mann-Whitney tests (pigs) (P < 0.05). Pollution was higher during induction when compared with baseline regardless of the mask type used but it was only statistically significant in dogs and pigs. Pollution was lower during induction with double versus single masks but it was only significant in pigs. Despite the lack of statistical significance, large and consistent differences were noted in all species, hence using scavenging masks is recommended to reduce isoflurane workplace pollution. PMID:21586515

  16. Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium.

    PubMed

    Vanlinthout, L E; Booij, L H; van Egmond, J; Robertson, E N

    1996-03-01

    We have compared the ability of equipotent concentrations of isoflurane and sevoflurane to enhance the effect of non-depolarizing neuromuscular blocking drugs. Ninety ASA I and II patients of both sexes, aged 18-50 yr, were stratified into three blocker groups (Vec, Pan and Atr), to undergo neuromuscular block with vecuronium (n = 30), pancuronium (n = 30) or atracurium (n = 30), respectively. Within each group, patients were allocated randomly to one of three anaesthetic subgroups to undergo maintenance of anaesthesia with: (1) alfentanil-nitrous oxide-oxygen (n = 10); (2) alfentanil-nitrous oxide-oxygen-isoflurane (n = 10); or (3) alfentanil-nitrous oxide-oxygen-sevoflurane (n = 10) anaesthesia. During maintenance of anaesthesia, end-tidal concentrations of isoflurane, sevoflurane and nitrous oxide were 0.95, 1.70 and 70%, respectively. Both the evoked integrated electromyogram and mechanomyogram of the adductor pollicis brevis muscle were measured simultaneously. In the Vec and Pan groups, a total dose of 40 micrograms kg-1 of vecuronium or pancuronium, respectively, was given, and in the Atr group a total dose of atracurium 100 micrograms kg-1. Each blocker was given in four equal doses and administered cumulatively. We showed that 0.95% isoflurane and 1.70% sevoflurane (corresponding to 0.8 MAC of each inhalation anaesthetic, omitting the MAC contribution of nitrous oxide) augmented and prolonged the neuromuscular block produced by vecuronium, pancuronium and atracurium to a similar degree. PMID:8785139

  17. Fatal Alveolar Echinococcosis of the Lumbar Spine

    PubMed Central

    Keutgens, Aurore; Simoni, Paolo; Detrembleur, Nancy; Frippiat, Frédéric; Giot, Jean-Baptiste; Spirlet, François; Aghazarian, Saro; Descy, Julie; Meex, Cécile; Huynen, Pascale; Melin, Pierrette; Müller, Norbert; Gottstein, Bruno; Carlier, Yves

    2013-01-01

    For the last 10 years, the southern part of Belgium has been recognized as a low-risk area of endemicity for alveolar echinococcosis. This infection, caused by Echinococcus multilocularis, usually induces a severe liver condition and can sometimes spread to other organs. However, alveolar echinococcosis involving bones has been described only very rarely. Here, a fatal case of spondylodiscitis due to E. multilocularis contracted in southern Belgium is reported. PMID:23175265

  18. Are Panoramic Radiographs Reliable to Diagnose Mild Alveolar Bone Resorption?

    PubMed Central

    Semenoff, Larissa; Semenoff, Tereza Aparecida Delle; Pedro, Fabio Luiz Miranda; Volpato, Evaristo Ricci; Machado, Maria Aparecida de Andrade Moreira; Borges, Álvaro Henrique; Semenoff-Segundo, Alex

    2011-01-01

    It is extremely important to assess variations between the most used radiographs in dental practice, since minimum distortion on obtained images may change diagnosis, treatment plan, and prognosis for the patient. For this, the distance between the enamel-cementum junction and the alveolar bone crest was measured on conventional and digitized periapical, bitewing, and panoramic radiographs and compared among them. From a total of 1484 records, 39 sets of radiographs that fulfilled the inclusion criteria of the study sample were selected. The measurements were grouped according to the intensity of bone loss. Statistically significant difference was found in the averages of the measurements assessed in radiographs with absence of bone loss between conventional panoramic and periapical radiographs, between digitized panoramic and periapical radiographs and between digitized bitewing and panoramic radiographs. By analyzing the results of this work and considering the research protocol used, one can conclude that small losses in height of alveolar bone crest observed in panoramic radiographs should be cautiously evaluated, as they may be overestimated. PMID:21991470

  19. Are panoramic radiographs reliable to diagnose mild alveolar bone resorption?

    PubMed

    Semenoff, Larissa; Semenoff, Tereza Aparecida Delle; Pedro, Fabio Luiz Miranda; Volpato, Evaristo Ricci; Machado, Maria Aparecida de Andrade Moreira; Borges, Alvaro Henrique; Semenoff-Segundo, Alex

    2011-01-01

    It is extremely important to assess variations between the most used radiographs in dental practice, since minimum distortion on obtained images may change diagnosis, treatment plan, and prognosis for the patient. For this, the distance between the enamel-cementum junction and the alveolar bone crest was measured on conventional and digitized periapical, bitewing, and panoramic radiographs and compared among them. From a total of 1484 records, 39 sets of radiographs that fulfilled the inclusion criteria of the study sample were selected. The measurements were grouped according to the intensity of bone loss. Statistically significant difference was found in the averages of the measurements assessed in radiographs with absence of bone loss between conventional panoramic and periapical radiographs, between digitized panoramic and periapical radiographs and between digitized bitewing and panoramic radiographs. By analyzing the results of this work and considering the research protocol used, one can conclude that small losses in height of alveolar bone crest observed in panoramic radiographs should be cautiously evaluated, as they may be overestimated. PMID:21991470

  20. Telomere dysfunction causes alveolar stem cell failure.

    PubMed

    Alder, Jonathan K; Barkauskas, Christina E; Limjunyawong, Nathachit; Stanley, Susan E; Kembou, Frant; Tuder, Rubin M; Hogan, Brigid L M; Mitzner, Wayne; Armanios, Mary

    2015-04-21

    Telomere syndromes have their most common manifestation in lung disease that is recognized as idiopathic pulmonary fibrosis and emphysema. In both conditions, there is loss of alveolar integrity, but the underlying mechanisms are not known. We tested the capacity of alveolar epithelial and stromal cells from mice with short telomeres to support alveolar organoid colony formation and found that type 2 alveolar epithelial cells (AEC2s), the stem cell-containing population, were limiting. When telomere dysfunction was induced in adult AEC2s by conditional deletion of the shelterin component telomeric repeat-binding factor 2, cells survived but remained dormant and showed all the hallmarks of cellular senescence. Telomere dysfunction in AEC2s triggered an immune response, and this was associated with AEC2-derived up-regulation of cytokine signaling pathways that are known to provoke inflammation in the lung. Mice uniformly died after challenge with bleomycin, underscoring an essential role for telomere function in AEC2s for alveolar repair. Our data show that alveoloar progenitor senescence is sufficient to recapitulate the regenerative defects, inflammatory responses, and susceptibility to injury that are characteristic of telomere-mediated lung disease. They suggest alveolar stem cell failure is a driver of telomere-mediated lung disease and that efforts to reverse it may be clinically beneficial. PMID:25840590

  1. Review of secondary alveolar cleft repair

    PubMed Central

    Cho-Lee, Gui-Youn; García-Díez, Eloy-Miguel; Nunes, Richard-Agostinho; Martí-Pagès, Carles; Sieira-Gil, Ramón; Rivera-Baró, Alejandro

    2013-01-01

    Introduction: The alveolar cleft is a bony defect that is present in 75% of the patients with cleft lip and palate. Although secondary alveolar cleft repair is commonly accepted for these patients, nowadays, controversy still remains regarding the surgical technique, the timing of the surgery, the donor site, and whether the use of allogenic materials improve the outcomes. The purpose of the present review was to evaluate the protocol, the surgical technique and the outcomes in a large population of patients with alveolar clefts that underwent secondary alveolar cleft repair. Materials and Methods: A total of 109 procedures in 90 patients with alveolar cleft were identified retrospectively after institutional review board approval was obtained. The patients were treated at a single institution during a period of 10 years (2001-2011). Data were collected regarding demographics, type of cleft, success parameters of the procedure (oronasal fistulae closure, unification of the maxillary segments, eruption and support of anterior teeth, support to the base of the nose, normal ridge form for prosthetic rehabilitation), donor site morbidity, and complications. Pre- and postoperative radiological examination was performed by means of orthopantomogram and computed tomography (CT) scan. Results: The average patient age was 14.2 years (range 4–21.3 years). There were 4 right alveolar-lip clefts, 9 left alveolar-lip clefts, 3 bilateral alveolar-lip clefts, 18 right palate-lip clefts, 40 left palate-lip clefts and 16 bilateral palate-lip clefts. All the success parameters were favorable in 87 patients. Iliac crest bone grafts were employed in all cases. There were three bone graft losses. In three cases, allogenic materials used in a first surgery performed in other centers, underwent infection and lacked consolidation. They were removed and substituted by autogenous iliac crest bone graft. Conclusions: The use of autogenous iliac crest for secondary alveolar bone grafting

  2. Suppression of parasympathetic reflex vasodilatation in the lower lip of the cat by isoflurane, propofol, ketamine and pentobarbital: implications for mechanisms underlying the production of anaesthesia.

    PubMed

    Ito, Y; Izumi, H; Sato, M; Karita, K; Iwatsuki, N

    1998-10-01

    We have compared the effects of isoflurane, propofol, ketamine and pentobarbital on parasympathetic reflex vasodilatation to investigate their involvement in GABA-mediated synaptic inhibition, enhancement of which is thought to underlie the action of many anaesthetic agents. In cats anaesthetized with urethane-alpha-chloralose, parasympathetic reflex vasodilation in the ipsilateral lower lip was elicited by electrical stimulation of the central cut end of the lingual nerve. Isoflurane and pentobarbital both produced marked dose-dependent inhibition of this vasodilator response. In contrast, propofol and ketamine had no effect on parasympathetic reflex vasodilation. Administration of a GABA antagonist (picrotoxin) reversed the inhibition produced by isoflurane (previous results) and pentobarbital (present study). Our results suggest that isoflurane and pentobarbitone inhibit parasympathetic reflex vasodilatation via a GABA-mediated mechanism, but that propofol and ketamine have no such effect. Our results with propofol cast doubt on its presumed mechanism of action as an anaesthetic. PMID:9924233

  3. Effect of Orphanin FQ/Nociceptin (OFQ/N) and Isoflurane on the Prolactin Secretory Response in OFQ/N Knockout Mice

    PubMed Central

    Zullig, Kelly L.; Murphree, Emily; Reinscheid, Rainer K.; Janik, James; Callahan, Phyllis

    2007-01-01

    The prolactin secretory response to subcutaneous injection of orphanin FQ/nociceptin (OFQ/N) was measured in wild-type and OFQ/N knockout mice. These injections were given with and without isoflurane anesthesia, to determine if isoflurane would affect the prolactin secretory response. OFQ/N injection significantly increased prolactin levels in males and females, regardless of genotype, with a more robust response in females. Isoflurane pretreatment did not affect prolactin levels in controls or in animals injected with OFQ/N. This is the first report that exogenously administered OFQ/N stimulates prolactin secretion in mice and that brief isoflurane exposure does not significantly affect this response. PMID:17698246

  4. Inhaled Anesthetic Responses of Recombinant Receptors and Knockin Mice Harboring α2(S270H/L277A) GABAA Receptor Subunits That Are Resistant to Isoflurane

    PubMed Central

    Werner, D. F.; Swihart, A.; Rau, V.; Jia, F.; Borghese, C. M.; McCracken, M. L.; Iyer, S.; Fanselow, M. S.; Oh, I.; Sonner, J. M.; Eger, E. I.; Harrison, N. L.; Harris, R. A.

    2011-01-01

    The mechanism by which the inhaled anesthetic isoflurane produces amnesia and immobility is not understood. Isoflurane modulates GABAA receptors (GABAA-Rs) in a manner that makes them plausible targets. We asked whether GABAA-R α2 subunits contribute to a site of anesthetic action in vivo. Previous studies demonstrated that Ser270 in the second transmembrane domain is involved in the modulation of GABAA-Rs by volatile anesthetics and alcohol, either as a binding site or a critical allosteric residue. We engineered GABAA-Rs with two mutations in the α2 subunit, changing Ser270 to His and Leu277 to Ala. Recombinant receptors with these mutations demonstrated normal affinity for GABA, but substantially reduced responses to isoflurane. We then produced mutant (knockin) mice in which this mutated subunit replaced the wild-type α2 subunit. The adult mutant mice were overtly normal, although there was evidence of enhanced neonatal mortality and fear conditioning. Electrophysiological recordings from dentate granule neurons in brain slices confirmed the decreased actions of isoflurane on mutant receptors contributing to inhibitory synaptic currents. The loss of righting reflex EC50 for isoflurane did not differ between genotypes, but time to regain the righting reflex was increased in N2 generation knockins. This effect was not observed at the N4 generation. Isoflurane produced immobility (as measured by tail clamp) and amnesia (as measured by fear conditioning) in both wild-type and mutant mice, and potencies (EC50) did not differ between the strains for these actions of isoflurane. Thus, immobility or amnesia does not require isoflurane potentiation of the α2 subunit. PMID:20807777

  5. Minimum Competency Testing. Update.

    ERIC Educational Resources Information Center

    Beard, Jacob G.

    During the last decade many school systems began to define minimum levels of competency for their students and to construct tests to measure whether students had achieved these minimums. Many states have passed laws which require high school students to pass minimum competency tests in order to graduate. This digest overviews four areas of…

  6. Influence of isoflurane on the diastolic pressure-flow relationship and critical occlusion pressure during arterial CABG surgery: a randomized controlled trial

    PubMed Central

    Hinz, José; Hanekop, Gerd G.; Weyland, Andreas; Popov, Aron F.; Schmitto, Jan D.; Bauer, Martin; Kazmaier, Stephan

    2016-01-01

    The effects of isoflurane on the determinants of blood flow during Coronary Artery Bypass Graft (CABG) surgery are not completely understood. This study characterized the influence of isoflurane on the diastolic Pressure-Flow (P-F) relationship and Critical Occlusion Pressure (COP) during CABG surgery. Twenty patients undergoing CABG surgery were studied. Patients were assigned to an isoflurane or control group. Hemodynamic and flow measurements during CABG surgery were performed twice (15 minutes after the discontinuation of extracorporeal circulation (T15) and again 15 minutes later (T30)). The zero flow pressure intercept (a measure of COP) was extrapolated from a linear regression analysis of the instantaneous diastolic P-F relationship. In the isoflurane group, the application of isoflurane significantly increased the slope of the diastolic P-F relationship by 215% indicating a mean reduction of Coronary Vascular Resistance (CVR) by 46%. Simultaneously, the Mean Diastolic Aortic Pressure (MDAP) decreased by 19% mainly due to a decrease in the systemic vascular resistance index by 21%. The COP, cardiac index, heart rate, Left Ventricular End-Diastolic Pressure (LVEDP) and Coronary Sinus Pressure (CSP) did not change significantly. In the control group, the parameters remained unchanged. In both groups, COP significantly exceeded the CSP and LVEDP at both time points. We conclude that short-term application of isoflurane at a sedative concentration markedly increases the slope of the instantaneous diastolic P-F relationship during CABG surgery implying a distinct decrease with CVR in patients undergoing CABG surgery. PMID:26966644

  7. Isoflurane attenuates mouse microglial engulfment induced by lipopolysaccharide and interferon-γ possibly by inhibition of p38 mitogen-activated protein kinase.

    PubMed

    Ryu, Jung-Hee; Wang, Zhi; Fan, Dan; Han, Sung-Hee; Do, Sang-Hwan; Zuo, Zhiyi

    2016-09-28

    Microglial engulfment is a basic function to clean up dead and injured cells and invaders, such as bacteria. This study was designed to assess the effects of isoflurane on the microglial engulfment induced by lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) and the involvement of p38 mitogen-activated protein kinase (MAPK) in these effects. C8-B4 microglial cells were exposed to 1, 2, and 3% isoflurane at 2 h after the initiation of LPS (100 ng/ml) and IFN-γ (1 ng/ml) stimulation. Fluorescent immunostaining was performed to assess the percentage of cells with engulfment of fluorescent microspheres after stimulation for 24 h. P38 and phosphorylated p38 were determined by Western blotting. Isoflurane concentration dependently decreased microglial engulfment stimulated by LPS and IFN-γ. LPS and IFN-γ increased the phosphorylated p38 in microglial cells. This upregulation was decreased by isoflurane. SB203580, a p38 MAPK inhibitor, abolished the LPS-induced and IFN-γ-induced increase of engulfment activity, whereas anisomycin, a p38 MAPK activator, partly reversed the isoflurane-decreased microglial engulfment activity. These results suggest that isoflurane reduces LPS-induced and IFN-γ-induced microglial engulfment and that these effects may be mediated by inhibiting p38 MAPK. PMID:27513199

  8. Effect of Intermittent Positive Pressure Ventilation on Depth of Anaesthesia during and after Isoflurane Anaesthesia in Sulphur-Crested Cockatoos (Cacatua galerita galerita)

    PubMed Central

    2014-01-01

    This study aimed to determine the effect of intermittent positive pressure ventilation (IPPV) on the depth of inhalation anaesthesia in parrots. Anaesthesia was induced with 3.0% isoflurane in six Sulphur-crested Cockatoos (Cacatua galerita galerita) and maintained using either 1.5% or 3.0% during spontaneous ventilation (SV) or IPPV at 6 (IPPV-6) or 12 (IPPV-12) breaths per minute. The time taken for the appearance of somatic reflexes and the return of SV after IPPV was recorded. During recovery, the body jerk, beak, eye, and shivering reflexes appeared after 126 ± 27 s, 133 ± 26 s, 165 ± 34 s, and 165 ± 44 s, respectively. All cockatoos developed apnoea after IPPV-12 and only some did after IPPV-6. Return of SV after IPPV-12 was delayed compared to IPPV-6. Recovery times after the SV runs were significantly different between 1.5% and 3.0% isoflurane anaesthesia. Similarly, after IPPV, the recovery times were significantly different between 1.5% and 3.0% isoflurane anaesthesia. Recovery times after 3.0% inhaled isoflurane were longer than those of 1.5% inhaled isoflurane. In conclusion, cockatoos recovering from isoflurane anaesthesia are likely to exhibit body jerk, beak, eye, and shivering reflexes in that order. IPPV increases the depth of anaesthesia in a rate and dose-related manner and prolongs recovery. PMID:24587938

  9. Inferior Alveolar Nerve Injury after Mandibular Third Molar Extraction: a Literature Review

    PubMed Central

    Juodzbalys, Gintaras

    2014-01-01

    ABSTRACT Objectives The purpose of this study was to systematically review the comprehensive overview of literature data about injury to the inferior alveolar nerve after lower third molar extraction to discover the prevalence of injury, the risk factors, recovery rates, and alternative methods of treatment. Material and Methods Literature was selected through a search of PubMed electronic databases. Articles from January 2009 to June 2014 were searched. English language articles with a minimum of 6 months patient follow-up and injury analysis by patient’s reporting, radiographic, and neurosensory testing were selected. Results In total, 84 literature sources were reviewed, and 14 of the most relevant articles that are suitable to the criteria were selected. Articles were analyzed on men and women. The influence of lower third molar extraction (especially impacted) on the inferior alveolar nerve was clearly seen. Conclusions The incidence of injury to the inferior alveolar nerve after lower third molar extraction was about 0.35 - 8.4%. The injury of the inferior alveolar nerve can be predicted by various radiological signs. There are few risk factors that may increase the risk of injury to the nerve such as patients over the age of 24 years old, with horizontal impactions, and extraction by trainee surgeons. Recovery is preferable and permanent injury is very rare. PMID:25635208

  10. Lateralization Technique and Inferior Alveolar Nerve Transposition

    PubMed Central

    Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

    2016-01-01

    Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

  11. [Inferior alveolar nerve repositioning in implant surgery].

    PubMed

    Ardekian, L; Salnea, J; Abu el-Naaj, I; Gutmacher, T; Peled, M

    2001-04-01

    Severe resorption of the posterior mandible possesses one of the most difficult restorative challenges to the implant surgery today. This resorption may prevent the placement of dental implants without the potentially damage to the inferior alveolar nerve. To create the opportunity of insertion dental implants of adequately length in those cases, the technique of nerve repositioning has been advocated. The purpose of this article is to describe two cases of nerve repositioning combined with placement of dental implants. Both cases showed appropriate postoperative healing without damage to the inferior alveolar nerve. The inferior alveolar nerve repositioning technique seems to be an acceptable alternative to augmentation procedure prior to dental implants placement in cases exhibiting atrophic posterior mandibular ridges. PMID:11494807

  12. ALVEOLAR BREATH SAMPLING AND ANALYSIS IN HUMAN EXPOSURE ASSESSMENT STUDIES

    EPA Science Inventory

    Alveolar breath sampling and analysis can be extremely useful in exposure assessment studies involving volatile organic compounds (VOCs). Over recent years scientists from the EPA's National Exposure Research Laboratory have developed and refined an alveolar breath collection ...

  13. Remodeling of alveolar septa after murine pneumonectomy.

    PubMed

    Ysasi, Alexandra B; Wagner, Willi L; Bennett, Robert D; Ackermann, Maximilian; Valenzuela, Cristian D; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-06-15

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P < 0.01) and returned to baseline levels within 3 wk. Consistent with septal retraction, the postpneumonectomy alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P < 0.001). To identify clumped capillaries predicted by septal retraction, vascular casting, analyzed by both scanning electron microscopy and synchrotron imaging, demonstrated matted capillaries that were most prominent 3 days after pneumonectomy. Numerical simulations suggested that septal retraction could reflect increased surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  14. Increased alveolar plasminogen activator in early asbestosis

    SciTech Connect

    Cantin, A.; Allard, C.; Begin, R.

    1989-03-01

    Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.

  15. Simple bone augmentation for alveolar ridge defects.

    PubMed

    Haggerty, Christopher J; Vogel, Christopher T; Fisher, G Rawleigh

    2015-05-01

    Dental implant procedures, both surgical placement and preimplant bone augmentation, have become an integral aspect of the oral and maxillofacial surgeon's practice. The number of dental implants placed each year continues to increase as a result of increasing patient exposure and awareness of dental implants, the increased functional and esthetic dental demands of general practitioners and patients, the overall increase in age of the US patient population, and expanded insurance coverage of dental implant-related procedures. This article outlines relevant surgical procedures aimed toward reconstructing alveolar ridge defects to restore intra-arch alveolar discrepancies before restoration-driven dental implant placement. PMID:25951957

  16. Tobacco smoke and the pulmonary alveolar macrophage.

    PubMed

    Drath, D B; Davies, P; Karnovsky, M L; Huber, G L

    1979-01-01

    Our results indicate that tobacco smoke exposure to varying duration causes morphological, biochemical and functional alterations in pulmonary alveolar macrophages. The results of these changes is a population of alveolar macrophages made up of larger cells, with a reduced nucleus-cytoplasmic ratio, which are heavily loaded with heterolysosomes containing lipid. Though their fractional complement of mitochondria remains the same, an increase in the inner mitochondrial membrane surface area may be related to an enhanced oxidative metabolism. The cell is biochemically activated particularly following chronic exposure and is functionally impaired with respect to phagocytosis. PMID:232822

  17. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis

    PubMed Central

    Hahn, M. Frances; Abdelrazek, Hesham; Patel, Vipul J.; Walia, Rajat

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus. PMID:27213073

  18. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis.

    PubMed

    Tokman, Sofya; Hahn, M Frances; Abdelrazek, Hesham; Panchabhai, Tanmay S; Patel, Vipul J; Walia, Rajat; Omar, Ashraf

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus. PMID:27213073

  19. Pulmonary alveolar microlithiasis: a rare case report.

    PubMed

    Ahmad, Kaleem; Kumar Gupta, Mukesh; Dhungel, Kanchan; Lal Sah, Panna; Ansari, Sajid; Kumar Rauniyar, Raj

    2013-09-01

    Pulmonary alveolar microlithiasis is an uncommon infiltrative pulmonary disease characterized by deposition of microliths in the alveoli. We present the case of a young adult with complaints of shortness of breath on exertion. Chest radiograph showed innumerable small, dense nodules, diffusely involving both the lungs - predominantly in the lower zones. High-resolution CT scan illustrated widespread intra-alveolar microliths, diffuse ground-glass attenuation areas, septal thickening, and black pleural lines - predominantly in the basal regions. Transbronchial biopsy confirmed the diagnosis. PMID:24174699

  20. Pulmonary Alveolar Microlithiasis: A Rare Case Report

    PubMed Central

    Ahmad, Kaleem; Kumar Gupta, Mukesh; Dhungel, Kanchan; Lal Sah, Panna; Ansari, Sajid; Kumar Rauniyar, Raj

    2013-01-01

    Pulmonary alveolar microlithiasis is an uncommon infiltrative pulmonary disease characterized by deposition of microliths in the alveoli. We present the case of a young adult with complaints of shortness of breath on exertion. Chest radiograph showed innumerable small, dense nodules, diffusely involving both the lungs - predominantly in the lower zones. High-resolution CT scan illustrated widespread intra-alveolar microliths, diffuse ground-glass attenuation areas, septal thickening, and black pleural lines - predominantly in the basal regions. Transbronchial biopsy confirmed the diagnosis. PMID:24174699

  1. BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice.

    PubMed

    Wu, Jing; Zhang, Mingqiang; Li, Huihui; Sun, Xiaoru; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu

    2016-05-15

    Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia. PMID:26944333

  2. Chemical immobilization and anesthesia of free-living aardvarks (Orycteropus afer) with ketamine-medetomidine-midazolam and isoflurane.

    PubMed

    Rey, Benjamin; Costello, Mary-Ann; Fuller, Andrea; Haw, Anna; Hetem, Robyn S; Mitchell, Duncan; Meyer, Leith C R

    2014-10-01

    Abstract We evaluated the effectiveness of a ketamine-medetomidine-midazolam drug combination administered intramuscularly by remote injection followed by isoflurane anesthesia in free-living aardvarks (Orycteropus afer). Seven aardvarks weighing 33-45 kg were immobilized to perform surgical implantation of temperature loggers using 3.8 mg/kg ketamine, 0.1 mg/kg medetomidine, and 0.25 mg/kg midazolam. Immobilized aardvarks were transported to a surgical theater and received 0.5-1% isoflurane in oxygen after tracheal intubation. After surgery, medetomidine was antagonized with 0.5 mg/kg atipamezole, and aardvarks were released at the site of capture. We recorded induction and recovery times, clinical and physiologic parameters, and conducted blood gas analyses before and during isoflurane administration. Aardvarks showed initial effects within 3 min and reached lateral recumbency within 7 min after drug administration. Heart rate (50-67 beats/min), respiratory rate (10-15 breaths/min), oxygen hemoglobin saturation (SaO2; 90-97%), and rectal temperature (34.0-37.5 C) were within acceptable physiologic ranges. Mean arterial blood pressure was initially high (146 ± 12 mmHg), but the hypertension resolved over time. Rectal temperature dropped significantly during anesthesia. Four animals had to be treated to relieve apnea. Blood gas analyses revealed mild to moderate hypercapnia but no hypoxaemia. The ketamine-medetomidine-midazolam combination provided effective immobilization. Combined with a low concentration of isoflurane, it can be used for prolonged surgical procedures in wild aardvarks. However, caution is needed, and monitoring of clinical parameters is required. PMID:25014906

  3. Biphasic change of progenitor proliferation in dentate gyrus after single dose of isoflurane in young adult rats

    PubMed Central

    Lin, Nan; Moon, Tiffany Sun; Stratmann, Greg; Sall, Jeffrey W.

    2013-01-01

    Background Isoflurane exposure causes improvement in long-term neurocognitive function in young adult rats, this is associated with an increase in dentate gyrus progenitor proliferation 4 days after anesthesia. However, the number of new neurons, that were born from cells that incorporated bromodeoxyuridine 4 days after anesthesia is not affected by anesthesia. We tested the hypothesis that progenitor proliferation continues to increase past 4 days, which would imply the possibility that the number of new neurons after anesthesia could be increased if bromodeoxyuridine labeling occurred at a later time point. Methods Bromodeoxyuridine was injected at 0, 1, 2, 4, 9, 16 days after 4 hours of isoflurane exposure to 60-day old rats. Brains were harvested 2 hours later, immunohistochemically stained, and the number of bromodeoxyuridine-positive cells in the dentate gyrus was assessed microscopically. Results After 4 hours of exposure to isoflurane in 60-day old rats, the number of bromodeoxyuridine-positive cells decreased on days 0–2, then increased on day 4 significantly, and regressed toward the control level on day 9 and 16. Conclusions Anesthesia-induced progenitor proliferation in the dentate gyrus was not sustained 9 days after anesthesia. We interpret these results to signify that an anesthetic effect on neurogenesis likely does not play a critical role in the previously observed isoflurane-induced long-term improvement in neurocognitive function in 60-day old rats and that the transient increase in progenitor proliferation serves to replenish the pool of neural stem cells. The mechanism of anesthesia-induced improvement in cognition of young adult rats remains elusive. PMID:23752046

  4. Cardiovascular effects of intravenous bolus administration and infusion of ketamine-midazolam in isoflurane-anesthetized dogs.

    PubMed

    Jacobson, J D; Hartsfield, S M

    1993-10-01

    Cardiovascular effects of IV administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) were determined in 12 healthy isoflurane-anesthetized (1.7% end-tidal concentration) dogs. Six dogs received a ketamine-midazolam combination (K-M) as a bolus over 30 seconds and 6 dogs received K-M as an infusion over 15 minutes. Ketamine-midazolam combination as a bolus and an infusion caused early significant (P < 0.05) reductions in mean systemic blood pressure, cardiac index, and stroke index, which returned to baseline values near the end of the study. Heart rate decreased significantly (P < 0.05) in dogs of the infusion group and returned to the baseline value near the end of the study. One dog died after K-M bolus administration. Mean maximal decreases from baseline for systemic blood pressure, cardiac index, and stroke index were significantly (P < 0.05) greater in dogs of the bolus group than in dogs of the infusion group; therefore, cardiovascular effects of K-M after infusion were less severe than those after bolus. Base excess and pHa decreased significantly (P < 0.05) in the infusion group, although similar changes occurred in both groups. Four dogs were maintained with 1.7% end-tidal isoflurane to determine temporal effects of isoflurane; these dogs did not receive K-M. Increases in heart rate, cardiac index, stroke index, and left and right ventricular stroke work indexes were significant (P < 0.05) at various sample collection intervals, particularly during the later stages of the study. Isoflurane anesthesia effectively blocked the cardiostimulatory properties of K-M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8250398

  5. The effect of isoflurane anaesthesia and buprenorphine on the mouse grimace scale and behaviour in CBA and DBA/2 mice

    PubMed Central

    Miller, Amy; Kitson, Gemma; Skalkoyannis, Benjamin; Leach, Matthew

    2015-01-01

    Prevention or alleviation of pain in laboratory mice is a fundamental requirement of in vivo research. The mouse grimace scale (MGS) has the potential to be an effective and rapid means of assessing pain and analgesic efficacy in laboratory mice. Preliminary studies have demonstrated its potential utility for assessing pain in mouse models that involve potentially painful procedures. The next step in validation is to determine if the other procedures that are integral to these models, i.e. anaesthesia or analgesia, result in any changes in MGS score which would need to be taken into account when using this tool to assess post-procedural pain. Here, spontaneous behaviour and MGS data for CBA and DBA/2 mice were recorded at baseline and following either isoflurane anaesthesia (suitable to perform abdominal surgery) or 0.05 mg/kg s.c. buprenorphine. In line with previous studies, isoflurane anaesthesia alone had limited effects on the spontaneous behaviour in either strain of mice. Administration of buprenorphine resulted in increased periods of activity e.g. walking and chewing bedding in CBA mice. These effects were not demonstrated in DBA/2 mice. In comparison, buprenorphine alone had no impact on MGS score in either strain of mice, however DBA/2 mice showed a significant increase in MGS score following isoflurane anaesthesia. The presence of this increased MGS score must be taken into account when attempting to use the MGS to assess pain in DBA/2 mice. Further work should be carried out to establish the presence of this isoflurane effect in other strains and the potential influence of gender on the MGS. This further validation is necessary prior to implementation of this technique in clinical scenarios. PMID:26937061

  6. Intraoperative anesthetic management of patients undergoing glomus tumor resection using a low-dose isoflurane-fentanyl technique.

    PubMed

    Jellish, W S; Murdoch, J; Leonetti, J

    1994-01-01

    Glomus jugulare and vagale tumors present unique problems to both anesthesiologists and surgeons. The anesthetic plant must be tailored to each patient and provide hemodynamic stability, a consistent intraoperative environment, and rapid awakening after prolonged administration. In this report, we describe our anesthetic method used for paraganglioma resection, which utilizes a combination technique of low-dose isoflurane with a narcotic infusion initiated after bolus administration. Results from the last three patients anesthetized by this "balanced" technique were compared to a similar patient who received isoflurane anesthesia exclusively for a major portion of the surgical procedure. The patients receiving the balanced anesthesia required no hemodynamic support during the procedure and were awakened within 15 to 25 minutes of surgical completion. The patient receiving high-dose isoflurane, however, had a prolonged anesthetic wake-up time and did not follow verbal commands for approximately 12 hours after surgical completion. This patient also required hemodynamic support with a phenylephrine infusion during tumor resection. The balanced technique seems to be superior to a straight inhalational technique. Neurological assessment and intubation times after prolonged surgery were reduced with superb hemodynamic stability throughout. This anesthetic method produces a stable intraoperative environment and provides deep surgical anesthesia during periods when muscle relaxants cannot be utilized. PMID:17170932

  7. Intraoperative Anesthetic Management of Patients Undergoing Glomus Tumor Resection Using a Low-Dose Isoflurane-Fentanyl Technique

    PubMed Central

    Jellish, W.S.; Murdoch, J.; Leonetti, J.

    1994-01-01

    Glomus jugulare and vagale tumors present unique problems to both anesthesiologists and surgeons. The anesthetic plant must be tailored to each patient and provide hemodynamic stability, a consistent intraoperative environment, and rapid awakening after prolonged administration. In this report, we describe our anesthetic method used for paraganglioma resection, which utilizes a combination technique of low-dose isoflurane with a narcotic infusion initiated after bolus administration. Results from the last three patients anesthetized by this “balanced” technique were compared to a similar patient who received isoflurane anesthesia exclusively for a major portion of the surgical procedure. The patients receiving the balanced anesthesia required no hemodynamic support during the procedure and were awakened within 15 to 25 minutes of surgical completion. The patient receiving high-dose isoflurane, however, had a prolonged anesthetic wake-up time and did not follow verbal commands for approximately 12 hours after surgical completion. This patient also required hemodynamic support with a phenylephrine infusion during tumor resection. The balanced technique seems to be superior to a straight inhalational technique. Neurological assessment and intubation times after prolonged surgery were reduced with superb hemodynamic stability throughout. This anesthetic method produces a stable intraoperative environment and provides deep surgical anesthesia during periods when muscle relaxants cannot be utilized. PMID:17170932

  8. Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans

    PubMed Central

    Tian, Yi; Li, Haobo; Liu, Peiyu; Xu, Jun-mei; Irwin, Michael G.; Xia, Zhengyuan; Tian, Guogang

    2015-01-01

    Background. Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury. Methods and Results. Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. Conclusion. A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation. PMID:26273143

  9. Isoflurane does not vasodilate rat thoracic aortic rings by endothelium-derived relaxing factor or other cyclic GMP-mediated mechanisms.

    PubMed

    Brendel, J K; Johns, R A

    1992-07-01

    Endothelium-derived relaxing factor (EDRF) is a potent endogenous vasodilator that has been indirectly suggested to play a role in isoflurane-mediated vasodilation. To examine directly the possible role of EDRF in isoflurane-mediated vasodilation, isolated rat thoracic aortic rings were suspended for isometric tension measurements, equilibrated to a resting tension of 2 g, and constricted with a 50% maximal concentration (EC50) dose of phenylephrine or KCl. Three groups of rings were studied: endothelium-intact, endothelium-denuded, and endothelium-intact rings treated with nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of EDRF synthase. Isoflurane was then added at 1, 2, and 3% in a cumulative manner, allowing 10 min for each concentration to equilibrate. Indomethacin was present in all experiments to prevent the formation of vasoactive prostanoid metabolites. Since EDRF causes vascular relaxation by stimulating soluble guanylyl cyclase and increasing cyclic GMP, the effect of isoflurane on vascular ring cyclic GMP content was determined as an additional indicator of EDRF-mediated dilation. Rings with intact and denuded endothelium were isolated as described above, constricted with phenylephrine, and challenged with methacholine (positive control) or 1, 2, or 3% isoflurane. After 8 min exposure, the rings were flash-frozen in dry-ice-cooled acetone and homogenized in 1 N HCl for subsequent analysis of cyclic GMP content by radioimmunoassay. Isoflurane caused dose-dependent vasodilation of both KCl- and phenylephrine-constricted rings. In the phenylephrine group, at 2% and 3% isoflurane, endothelium-denuded and L-NAME-treated rings relaxed to a greater extent than endothelium-intact rings (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1319121

  10. Inter- and Intra-Subunit Butanol/Isoflurane Sites of Action in the Human Glycine Receptor

    PubMed Central

    McCracken, Mandy L.; Gorini, Giorgio; McCracken, Lindsay M.; Mayfield, R. Dayne; Harris, R. Adron; Trudell, James R.

    2016-01-01

    Glycine receptors (GlyRs) mediate inhibitory neurotransmission and are targets for alcohols and anesthetics in brain. GlyR transmembrane (TM) domains contain critical residues for alcohol/anesthetic action: amino acid A288 in TM3 forms crosslinks with TM1 (I229) in the adjacent subunit as well as TM2 (S267) and TM4 (Y406, W407, I409, Y410) in the same subunit. We hypothesized that these residues may participate in intra-subunit and inter-subunit sites of alcohol/anesthetic action. The following double and triple mutants of GLRA1 cDNA (encoding human glycine receptor alpha 1 subunit) were injected into Xenopus laevis oocytes: I229C/A288C, I229C/A288C/C290S, A288C/Y406C, A288C/W407C, A288C/I409C, and A288C/Y410C along with the corresponding single mutants and wild-type GLRA1. Butanol (22 mM) or isoflurane (0.6 mM) potentiation of GlyR-mediated currents before and after application of the cysteine crosslinking agent HgCl2 (10 μM) was measured using two-electrode voltage clamp electrophysiology. Crosslinking nearly abolished butanol and isoflurane potentiation in the I229C/A288C and I229C/A288C/C290S mutants but had no effect in single mutants or wild-type. Crosslinking also inhibited butanol and isoflurane potentiation in the TM3-4 mutants (A288C/Y406C, A288C/W407C, A288C/I409C, A288C/Y410C) with no effect in single mutants or wild-type. We extracted proteins from oocytes expressing I229C/288C, A288C/Y410C, or wild-type GlyRs, used mass spectrometry to verify their expression and possible inter-subunit dimerization, plus immunoblotting to investigate the biochemical features of proposed crosslinks. Wild-type GlyR subunits measured about 50 kDa; after crosslinking, the dimeric/monomeric 100:50 kDa band ratio was significantly increased in I229C/288C but not A288C/Y410C mutants or wild-type, providing support for TM1-3 inter-subunit and TM3-4 intra-subunit crosslinking. A GlyR homology model based on the GluCl template provides further evidence for a multi-site model

  11. Inter- and Intra-Subunit Butanol/Isoflurane Sites of Action in the Human Glycine Receptor.

    PubMed

    McCracken, Mandy L; Gorini, Giorgio; McCracken, Lindsay M; Mayfield, R Dayne; Harris, R Adron; Trudell, James R

    2016-01-01

    Glycine receptors (GlyRs) mediate inhibitory neurotransmission and are targets for alcohols and anesthetics in brain. GlyR transmembrane (TM) domains contain critical residues for alcohol/anesthetic action: amino acid A288 in TM3 forms crosslinks with TM1 (I229) in the adjacent subunit as well as TM2 (S267) and TM4 (Y406, W407, I409, Y410) in the same subunit. We hypothesized that these residues may participate in intra-subunit and inter-subunit sites of alcohol/anesthetic action. The following double and triple mutants of GLRA1 cDNA (encoding human glycine receptor alpha 1 subunit) were injected into Xenopus laevis oocytes: I229C/A288C, I229C/A288C/C290S, A288C/Y406C, A288C/W407C, A288C/I409C, and A288C/Y410C along with the corresponding single mutants and wild-type GLRA1. Butanol (22 mM) or isoflurane (0.6 mM) potentiation of GlyR-mediated currents before and after application of the cysteine crosslinking agent HgCl2 (10 μM) was measured using two-electrode voltage clamp electrophysiology. Crosslinking nearly abolished butanol and isoflurane potentiation in the I229C/A288C and I229C/A288C/C290S mutants but had no effect in single mutants or wild-type. Crosslinking also inhibited butanol and isoflurane potentiation in the TM3-4 mutants (A288C/Y406C, A288C/W407C, A288C/I409C, A288C/Y410C) with no effect in single mutants or wild-type. We extracted proteins from oocytes expressing I229C/288C, A288C/Y410C, or wild-type GlyRs, used mass spectrometry to verify their expression and possible inter-subunit dimerization, plus immunoblotting to investigate the biochemical features of proposed crosslinks. Wild-type GlyR subunits measured about 50 kDa; after crosslinking, the dimeric/monomeric 100:50 kDa band ratio was significantly increased in I229C/288C but not A288C/Y410C mutants or wild-type, providing support for TM1-3 inter-subunit and TM3-4 intra-subunit crosslinking. A GlyR homology model based on the GluCl template provides further evidence for a multi-site model

  12. Alveolar mechanics using realistic acinar models

    NASA Astrophysics Data System (ADS)

    Kumar, Haribalan; Lin, Ching-Long; Tawhai, Merryn H.; Hoffman, Eric A.

    2009-11-01

    Accurate modeling of the mechanics in terminal airspaces of the lung is desirable for study of particle transport and pathology. The flow in the acinar region is traditionally studied by employing prescribed boundary conditions to represent rhythmic breathing and volumetric expansion. Conventional models utilize simplified spherical or polygonal units to represent the alveolar duct and sac. Accurate prediction of flow and transport characteristics may require geometries reconstructed from CT-based images and serve to understand the importance of physiologically realistic representation of the acinus. In this effort, we present a stabilized finite element framework, supplemented with appropriate boundary conditions at the alveolar mouth and septal borders for simulation of the alveolar mechanics and the resulting airflow. Results of material advection based on Lagrangian tracking are presented to complete the study of transport and compare the results with simplified acinar models. The current formulation provides improved understanding and realization of a dynamic framework for parenchymal mechanics with incorporation of alveolar pressure and traction stresses.

  13. Teaching Alveolar Ventilation with Simple, Inexpensive Models

    ERIC Educational Resources Information Center

    DiCarlo, Stephen E.

    2008-01-01

    When teaching and learning about alveolar ventilation with our class of 300 first-year medical students, we use four simple, inexpensive "models." The models, which encourage research-oriented learning and help our students to understand complex ideas, are distributed to the students before class. The students anticipate something new every day,…

  14. Selective alveolar corticotomy to intrude overerupted molars.

    PubMed

    Oliveira, Dauro Douglas; de Oliveira, Bruno Franco; de Araújo Brito, Helio Henrique; de Souza, Margareth Maria Gomes; Medeiros, Paulo José

    2008-06-01

    Orthodontic intrusion of overerupted molars in adults is challenging for most clinicians. Efficient intrusion can be achieved by combining selective alveolar corticotomies with a modified full-coverage maxillary splint to reduce surgical risks, treatment time, and costs for both orthodontists and patients. PMID:18538256

  15. Alveolar proteinosis associated with aluminium dust inhalation.

    PubMed

    Chew, R; Nigam, S; Sivakumaran, P

    2016-08-01

    Secondary alveolar proteinosis is a rare lung disease which may be triggered by a variety of inhaled particles. The diagnosis is made by detection of anti-granulocyte-macrophage colony-stimulating factor antibodies in bronchoalveolar lavage fluid, which appears milky white and contains lamellar bodies. Aluminium has been suggested as a possible cause, but there is little evidence in the literature to support this assertion. We report the case of a 46-year-old former boilermaker and boat builder who developed secondary alveolar proteinosis following sustained heavy aluminium exposure. The presence of aluminium was confirmed both by histological examination and metallurgical analysis of a mediastinal lymph node. Despite cessation of exposure to aluminium and treatment with whole-lung lavage which normally results in improvements in both symptoms and lung function, the outcome was poor and novel therapies are now being used for this patient. It may be that the natural history in aluminium-related alveolar proteinosis is different, with the metal playing a mediating role in the disease process. Our case further supports the link between aluminium and secondary alveolar proteinosis and highlights the need for measures to prevent excessive aluminium inhalation in relevant industries. PMID:27099254

  16. Secondary pulmonary alveolar proteinosis in hematologic malignancies.

    PubMed

    Chaulagain, Chakra P; Pilichowska, Monika; Brinckerhoff, Laurence; Tabba, Maher; Erban, John K

    2014-12-01

    Pulmonary alveolar proteinosis (PAP), characterized by deposition of intra-alveolar PAS positive protein and lipid rich material, is a rare cause of progressive respiratory failure first described by Rosen et al. in 1958. The intra-alveolar lipoproteinaceous material was subsequently proven to have been derived from pulmonary surfactant in 1980 by Singh et al. Levinson et al. also reported in 1958 the case of 19-year-old female with panmyelosis afflicted with a diffuse pulmonary disease characterized by filling of the alveoli with amorphous material described as "intra-alveolar coagulum". This is probably the first reported case of PAP in relation to hematologic malignancy. Much progress has been made on PAP first described by Rosen which is currently classified as idiopathic or primary or autoimmune PAP. Idiopathic PAP occurs as a result of auto-antibodies directed against granulocyte-macrophage colony stimulating factor (GM-CSF) impeding the surfactant clearing function of alveolar macrophages leading to progressive respiratory failure. Whole lung lavage and GM-CSF therapy has improved outcomes in patients with idiopathic PAP. Despite major advancement in the management of hematologic malignancy and its complications, little is known about the type of PAP first described by Levinson and now known as secondary PAP; a term also used when PAP occurs due to other causes such as occupational dusts. In this article we review and analyze the limited literature available in secondary PAP due to hematologic malignancies and present a case of PAP associated with chronic lymphocytic leukemia successfully treated with bendamustine and rituximab. PMID:25300566

  17. Disruption of Hippocampal Neuregulin 1-ErbB4 Signaling Contributes to the Hippocampus-dependent Cognitive Impairment Induced by Isoflurane in Aged Mice

    PubMed Central

    Li, Xiao-Min; Su, Fan; Ji, Mu-Huo; Zhang, Guang-Fen; Qiu, Li-Li; Jia, Min; Gao, Jun; Xie, Zhongcong; Yang, Jian-Jun

    2014-01-01

    Background A prolonged isoflurane exposure may lead to cognitive decline in rodents. Neuregulin 1 (NRG1)-ErbB4 signaling plays a key role in the modulation of hippocampal synaptic plasticity through regulating the neurotransmission. We hypothesized hippocampal NRG1-ErbB4 signaling is involved in isoflurane-induced cognitive impairments in aged mice. Methods Fourteen-month old C57BL/6 mice were randomized to receive 100% O2 exposure, vehicle injection after 100% O2 exposure, vehicle injection after exposure to isoflurane carried by 100% O2, NRG1-β1 injection after exposure to isoflurane carried by 100% O2, and NRG1-β1 and an ErbB4 inhibitor AG1478 injection after exposure to isoflurane carried by 100% O2. Fear conditioning test was used to assess the cognitive function of mice 48 h post-exposure. The brain tissues were harvested 48 h post-exposure to determine the levels of NRG1, ErbB4, p-ErbB4, parvalbumin, and glutamic acid decarboxylase (GAD) 67 in the hippocampus using western blotting, enzyme-linked immunosorbent assay, and immunofluorescence. Results The percentage of freezing time to context was decreased from 50.28 ± 11.53% to 30.82 ± 10.00% and the hippocampal levels of NRG1, p-ErbB4/ErbB4, parvalbumin, and GAD67 were decreased from 172.79 ± 20.85 ng/g, 69.15 ± 12.20%, 101.68 ± 11.21%, and 104.71 ± 6.85%, to 112.92 ± 16.65 ng/g, 42.26 ± 9.71%, 75.89 ± 10.26%, and 73.87 ± 16.89%, respectively, after isoflurane exposure. NRG1-β1 attenuated the isoflurane-induced hippocampus-dependent cognitive impairment and the declines in the hippocampal NRG1, p-ErbB4/ErbB4, parvalbumin, and GAD67. AG1478 inhibited the NRG1-β1’s rescuing effects. Conclusions Disruption of NRG1-ErbB4 signaling in the parvalbumin-positive interneurons might, at least partially, contribute to the isoflurane-induced hippocampus-dependent cognitive impairment after exposure to isoflurane carried by 100% O2 in aged mice. PMID:24589481

  18. Dose-dependent effects of isoflurane on regional activity and neural network function: A resting-state fMRI study of 14 rhesus monkeys: An observational study.

    PubMed

    Lv, Peilin; Xiao, Yuan; Liu, Bin; Wang, Yuqing; Zhang, Xiang; Sun, Huaiqiang; Li, Fei; Yao, Li; Zhang, Wenjing; Liu, Lu; Gao, Xin; Wu, Min; Tang, Yingying; Chen, Qin; Gong, Qiyong; Lui, Su

    2016-01-12

    The dose-dependent effect of isoflurane on cerebral regional activity and functional connectivity (FC) in 14 rhesus monkeys was investigated using resting-state functional MRI. Amplitude of low-frequency fluctuations (ALFF) decreased in the cerebellum, visual cortex, and cortico-subcortical network when the isoflurane dose changed from 1.0 to 1.3 MAC. ALFF decreased in the arousal system, cerebellum, sensory, visual areas, cortico-subcortical network and default mode network and increased in the bilateral dorsal prefrontal cortices, frontal eye fields and motor-related areas from 1.0 to 1.6 MAC. FC of the default mode network, frontal-parietal, cortico-subcortical, motor, sensory, auditory and visual areas was reduced when isoflurane increased from 1.0 to 1.3 MAC. FC decreased in more widespread areas, especially in regions of cortico-subcortical networks and limbic systems, when isoflurane further increased from 1.0 to 1.6 MAC. Both dose-dependent decreased and increased ALFF were separately observed, while FC deteriorated as the anesthesia deepened. These results suggest that changes continue to occur past the loss of consciousness, and the dose-dependent effects of isoflurane are different with regard to regional function and neural network integration. PMID:26633103

  19. Isoflurane anesthesia precipitates tauopathy and upper airways dysfunction in pre-symptomatic Tau.P301L mice: possible implication for neurodegenerative diseases.

    PubMed

    Menuet, Clément; Borghgraef, Peter; Voituron, Nicolas; Gestreau, Christian; Gielis, Lies; Devijver, Herman; Dutschmann, Mathias; Van Leuven, Fred; Hilaire, Gérard

    2012-04-01

    The postoperative cognitive decline resulting from volatile anesthesia is gaining acceptance as a major health problem. The common anesthetic isoflurane is suspected to precipitate neurodegeneration in Alzheimer's disease by unknown mechanisms. We previously validated that 8month old Tau.P301L mice suffer upper airways defects related to tauopathy within the Kolliker-Fuse nucleus that controls upper airways function. We now report that isoflurane anesthesia in young, pre-symptomatic Tau.P301L mice triggered precocious upper airways defects and tauopathy in several brainstem nuclei, including the nucleus ambiguus that contains upper airways motor neurons and the Kolliker-Fuse. The prescription drug memantine, identified as an NMDA receptor antagonist, prevented the post-anesthesia upper airways dysfunction and alleviated tauopathy in the nucleus ambiguus and Kolliker-Fuse. We further identified protocols of anesthesia in young Tau.P301L mice that mitigated adverse effects of isoflurane anesthesia. Thus, our experimental findings in a validated mouse model for tauopathy demonstrate the link between isoflurane anesthesia, earlier onset of tauopathy and earlier onset of functional deficits, highlight the implication of NMDA-receptors in the mechanisms mediating the adverse effects of isoflurane, and potentially identify safer protocols for anesthesia in patients with tauopathy. PMID:22316605

  20. Theoretical investigation on H abstraction reaction mechanisms and rate constants of Isoflurane with the OH radical

    NASA Astrophysics Data System (ADS)

    Ren, Hongjiang; Li, Xiaojun

    2015-12-01

    The mechanism of H abstraction reactions for Isoflurane with the OH radical was investigated using density functional theory and G3(MP2) duel theory methods. The geometrical structures of all the species were fully optimised at B3LYP/6-311++G** level of theory. Thermochemistry data were obtained by utilising the high accurate model chemistry method G3(MP2) combined with the standard statistical thermodynamic calculations. Gibbs free energies were used for the reaction channels analysis. All the reaction channels were confirmed throughout the intrinsic reaction coordinate analysis. The results show that two channels were obtained, which correspond to P(1) and P(2) with the respective activation barriers of 63.03 and 54.82 kJ/mol. The rate constants for the two channels over a wide temperature range of 298.15-2000 K were predicted and the calculated data are in agreement with the experimental one. The results show that P(2) is the dominant reaction channel under 800 K and above 800 K, it can be found that P(1) will be more preferable reaction channel.

  1. Covariation of pupillary and auditory cortical activity in rats under isoflurane anesthesia.

    PubMed

    Takahashi, H; Tokushige, H; Shiramatsu, T I; Noda, T; Kanzaki, R

    2015-08-01

    Very slow fluctuations of spontaneous activities significantly influence not only behavioral performance in a conscious state, but also neural activities in an unconscious state. Covariation of pupil and cortical activities may lend important insights into the state-dependent modulation of stimulus encoding, yet this phenomenon has received little attention, especially with regard to non-visual cortices. In the present study, we investigated co-fluctuation of pupil size and neural activity in the auditory cortex of rats under isoflurane anesthesia. Pupil fluctuation consisted of longitudinal irregular shifts, and 1-min cyclic modulations. Both spontaneous and auditory-evoked potentials (AEPs) covaried with the longitudinal fluctuation of pupil size, but not with the 1-min cycle. Pupil size exhibited a positive correlation with spontaneous activity and negative correlation with AEP amplitude, particularly when the pupil size was beyond the normal range. Stimulus-specific adaptation characterized using an oddball paradigm was less dependent on pupil size than AEP. In contrast to the cortical activity, heart rate covaried with pupil size with the 1-min oscillatory component, but not the non-oscillatory component. Furthermore, light exposure induced the pupil reflex through the autonomic system, but did not modify cortical activity, indicating that autonomic activity was not causing the cortical modulation. These results together suggest that cortical activities spontaneously covary with pupillary activity through central cholinergic modulation that triggers sympathetic nerve activation. Such a state-dependent property may be a confounding factor in cortical electrophysiology studies. PMID:25967265

  2. Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex.

    PubMed

    Masamoto, Kazuto; Kim, Tae; Fukuda, Mitsuhiro; Wang, Ping; Kim, Seong-Gi

    2007-04-01

    Functional magnetic resonance imaging (fMRI) in anesthetized rodents has been commonly performed with alpha-chloralose, which can be used only for terminal experiments. To develop a survival fMRI protocol, an isoflurane (ISO) -anesthetized rat model was systematically evaluated by simultaneous measurements of field potential (FP) and cerebral blood flow (CBF) in the somatosensory cortex. A conventional forepaw stimulation paradigm with 0.3 ms pulse width, 1.2 mA current, and 3 Hz frequency induced 54% less evoked FP and 84% less CBF response under ISO than alpha-chloralose. To improve stimulation-induced responses under ISO, 10-pulse stimulations were performed with variations of width, current, and frequency. For widths of 0.1-5.0 ms and currents of 0.4-2.0 mA, evoked FP and CBF increased similarly and reached a plateau. The evoked FP increased monotonically for intervals from 50 to 500 ms, but the CBF peaked at an interval of 83 ms (approximately 12 Hz frequency). These data suggest that different anesthetics profoundly affect FP and CBF responses in different ways, which requires optimizing stimulation parameters for each anesthetic. With the refined stimulation parameters, fMRI consistently detected a well-localized activation focus at the primary somatosensory cortex in ISO-anesthetized rats. Thus, the ISO-anesthetized rat model can be used for cerebrovascular activation studies, allowing repeated noninvasive survival experiments. PMID:16731882

  3. Anesthetic isoflurane attenuates activated microglial cytokine-induced VSC4.1 motoneuronal apoptosis

    PubMed Central

    Yang, Shuangmei; Liu, Jun; Zhang, Xiaoran; Tian, Jianmin; Zuo, Zhichao; Liu, Jingjing; Yue, Xiuqin

    2016-01-01

    Isoflurane (ISO) exhibits neuroprotective effects against inflammation and apoptosis. However, the role of ISO in motoneuronal apoptosis induced by activated microglia remains poorly studied. We investigated the protective effects of ISO on the apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons induced by lipopolysaccharide (LPS)-activated BV-2 microglia. Results indicated that ISO inhibited NF-κB activation and pro-inflammatory cytokine release in LPS-treated BV-2 microglia. Conditioned medium (CM) from activated BV-2 cells treated by ISO directly prevented VSC4.1 motoneurons from LPS-CM-induced neuronal apoptosis, as determined by the following: reductions in caspase-8, caspase-9, and caspase-3 activities; downregulation of pro-apoptotic procaspase-8, cleaved (cl)-caspase-8, procaspase-9, cl-caspase-9, caspase-3, cl-caspase-3, Bid, Bax, and cytochrome c expression; and upregulation of anti-apoptotic Bcl-2 expression in LPS-CM-cultured VSC4.1 motoneurons. Findings demonstrated that ISO inhibits BV-2 microglia activation and alleviates VSC4.1 motoneuronal apoptosis induced by microglial activation. These effects suggest that ISO can be used as an alternative agent for reducing neuronal apoptosis. PMID:27186270

  4. 2011 Sea Ice Minimum

    NASA Video Gallery

    This video shows Arctic sea ice from March 7, 2011, to Sept. 9, 2011, ending with a comparison of the 30-year average minimum extent, shown in yellow, and the Northwest Passage, in red. (no audio) ...

  5. Prospective Analysis of Secondary Alveolar Bone Grafting in Cleft Lip and Palate Patients

    PubMed Central

    Reddy, M Gokul Chandra; Babu, V Ramesh; Rao, V Eswar; Chaitanya, J Jaya; Allareddy, S; Reddy, C Charan Kumar

    2015-01-01

    Background: To assess the success of the uptake of bone graft in cleft alveolus of the cleft lip and palate patients, quantitatively through computed tomography (CT) scan 6 months postoperative. To assess the successful eruption of permanent lateral incisor or canine in the bone grafted area. Materials and Methods: The children age group of 9-21 years with unilateral cleft lip and palate came to the hospital, needing secondary alveolar bone grafting. A detailed history and clinical examination of the patient was taken. A 3D CT scan was taken and the volume of the cleft was measured pre-operatively. After ambulatory period, 3D CT scan of the alveolar cleft region was taken and volume of the bone grafted was measured and patient was discharged from the hospital. After 6 months, patient was recalled and again 3D CT scan was taken and the volume of remaining bone was measured. Results: The mean volume of the defect pre-operatively is 0.80 cm3 with a standard deviation of 0.36 cm3 with minimum volume of the defect 0.44 cm3 and maximum volume of the defect 1.60 cm3. The mean volume of the bone post-operative immediately after grafting is 1.01 cm3 with a standard deviation of 0.52 cm3 with minimum of bone volume is 0.48 cm3 and maximum of 2.06 cm3. The mean volume of the bone after 6 months after bone grafting is 0.54 cm3 with a standard deviation of 0.33 cm3, minimum bone volume of 0.22 cm3 and maximum bone volume of 1.42 cm3. Conclusion: The CT scan is a valuable radiographic imaging modality to assess and follow the clinical outcome of secondary alveolar bone grafting. PMID:25954076

  6. Treatment of Adult Primary Alveolar Proteinosis.

    PubMed

    Rodríguez Portal, José Antonio

    2015-07-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant-like lipoproteinaceous material in the distal air spaces and terminal bronchi, which may lead to impaired gas exchange. This accumulation of surfactant is due to decreased clearance by the alveolar macrophages. Its primary, most common form, is currently considered an autoimmune disease. Better knowledge of the causes of PAP have led to the emergence of alternatives to whole lung lavage, although this is still considered the treatment of choice. Most studies are case series, often with limited patient numbers, so the level of evidence is low. Since the severity of presentation and clinical course are variable, not all patients will require treatment. Due to the low level of evidence, some objective criteria based on expert opinion have been arbitrarily proposed in an attempt to define in which patients it is best to initiate treatment. PMID:25896950

  7. [Pulmonary alveolar proteinosis - a case report].

    PubMed

    Johannesdottir, Ragnheidur M; Jonsson, Steinn; Valsson, Felix; Hardardottir, Hronn; Amundadottir, Olof R; Bjornsson, Eythor; Nikulasson, Sigfus; Gudbjartsson, Tomas

    2014-11-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease of unknown origin, where an amorphous lipoprotein material accumulates in the alveoli of the lungs. We describe a young male with a four month history of progressive dyspnea, low grade fever, hypoxemia and weight loss. Chest X-ray showed diffuse interstitial and alveolar infiltrates in both lungs. The diagnosis of PAP was confirmed with trans-bronchial lung biopsy. Because of a deteriorating clinical course a whole lung lavage was performed. Under general anesthesia, both lungs were lavaged with warm saline in two different sessions with good results. Two years later the patient is almost free of symptoms and lung function has markedly improved. PMID:25413889

  8. Bilateral stony lung: pulmonary alveolar microlithiasis.

    PubMed

    Chandra, Subhash; Mohan, Anant; Guleria, Randeep; Das, Prasenjit; Sarkar, Chitra

    2009-01-01

    A 40-year-old male paddy field worker was referred for exertional shortness of breath and non-productive cough for 4 years. He had been treated for pulmonary tuberculosis twice. Chest radiograph showed extensive bilateral nodular opacities ("sandstorm-like") in the middle and lower lobe. Pulmonary function tests revealed a restrictive ventilatory defect. High resolution CT showed widespread nodular infiltration with "crazy paving" appearance and interrupted black pleura sign. This was confirmed as pulmonary alveolar microlithiasis (PAM) by trans-bronchial lung biopsy, which showed normal respiratory lining epithelium with dilated alveolar spaces containing many calcific bodies, some of which showed concentric calcification. The possibilities of silicosis (due to exposure to husk) and tuberculosis, both of which can mimic PAM clinically and radiologically, made this case a diagnostic challenge. PMID:21686505

  9. Bilateral stony lung: pulmonary alveolar microlithiasis

    PubMed Central

    Chandra, Subhash; Mohan, Anant; Guleria, Randeep; Das, Prasenjit; Sarkar, Chitra

    2009-01-01

    A 40-year-old male paddy field worker was referred for exertional shortness of breath and non-productive cough for 4 years. He had been treated for pulmonary tuberculosis twice. Chest radiograph showed extensive bilateral nodular opacities (“sandstorm-like”) in the middle and lower lobe. Pulmonary function tests revealed a restrictive ventilatory defect. High resolution CT showed widespread nodular infiltration with “crazy paving” appearance and interrupted black pleura sign. This was confirmed as pulmonary alveolar microlithiasis (PAM) by trans-bronchial lung biopsy, which showed normal respiratory lining epithelium with dilated alveolar spaces containing many calcific bodies, some of which showed concentric calcification. The possibilities of silicosis (due to exposure to husk) and tuberculosis, both of which can mimic PAM clinically and radiologically, made this case a diagnostic challenge. PMID:21686505

  10. Rare lung diseases II: Pulmonary alveolar proteinosis

    PubMed Central

    Juvet, Stephen C; Hwang, David; Waddell, Thomas K; Downey, Gregory P

    2008-01-01

    The present article is the second in a series on rare lung diseases. It focuses on pulmonary alveolar proteinosis (PAP), a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling through the granulocyte-macrophage colony-stimulating factor receptor, leading to macrophage and neutrophil dysfunction. This has spurred new therapeutic approaches to this disorder. The discussion of PAP will begin with a case report, then will highlight the classification of PAP and review recent insights into the pathogenesis of PAP. The approach to therapy and the prognosis of PAP will also be discussed. PMID:18551202

  11. Pelvic alveolar rhabdomyosarcoma in a young adult

    PubMed Central

    Reisner, David; Amadi, Chiemezie; Beckman, Irwin; Patel, Shweta; Surampudi, Ramana

    2015-01-01

    Rhabdomyosarcomas are soft-tissue tumors, rare in adults. Accounting for nearly 5% of childhood cancers, they represent less than 0.03% of adult malignancies (1, 2). Three different subtypes of rhabdomyosarcoma have been described (embryonal, alveolar and pleomorphic), making up approximately 50%, 30%, and 20% of the cases, respectively (3). Although the definitive diagnosis is made pathologically, some distinguishing features among these subtypes, and between rhabdomyosarcomas and other soft-tissue tumors, can be suggested on MRI and CT. We present an interesting case of a 20-year-old female with a locally aggressive pelvic alveolar rhabdomyosarcoma. While the prognosis has improved with newer treatment techniques, overall survival rates remain poor. Our case study presents typical features of a rare disease, which can often present a diagnostic dilemma for clinicians.

  12. Pulmonary alveolar proteinosis: time to shift?

    PubMed

    Papiris, Spyros A; Tsirigotis, Panagiotis; Kolilekas, Likurgos; Papadaki, Georgia; Papaioannou, Andriana I; Triantafillidou, Christina; Papaporfyriou, Anastasia; Karakatsani, Anna; Kagouridis, Konstantinos; Griese, Matthias; Manali, Effrosyni D

    2015-06-01

    Pulmonary alveolar proteinosis (PAP) is categorized into hereditary, secondary and autoimmune PAP (aPAP) types. The common pathogenesis is the ability of the alveolar macrophages to catabolize phagocytized surfactant is affected. Hereditary PAP is caused by mutations involving the GM-CSF signaling, particularly in genes for the GM-CSF receptor and sometimes by GATA2 mutations. Secondary PAP occurs in hematologic malignancies, other hematologic disorders, miscellaneous malignancies, fume and dust inhalation, drugs, autoimmune disorders and immunodeficiencies. aPAP is related to the production of GM-CSF autoantibodies. PAP is characterized morphologically by the inappropriate and progressive 'occupation' of the alveolar spaces by an excessive amount of unprocessed surfactant, limiting gas exchange and gradually exhausting the respiratory reserve. Myeloid cells' immunity deteriorates, increasing the risk of infections. Treatment of PAP is based on its etiology. In aPAP, recent therapeutic advances might shift the treatment option from the whole lung lavage procedure under general anesthesia to the inhalation of GM-CSF 'as needed'. PMID:25864717

  13. In situ methods for assessing alveolar mechanics.

    PubMed

    Wu, You; Perlman, Carrie E

    2012-02-01

    Lung mechanics are an important determinant of physiological and pathophysiological lung function. Recent light microscopy studies of the intact lung have furthered the understanding of lung mechanics but used methodologies that may have introduced artifacts. To address this concern, we employed a short working distance water immersion objective to capture confocal images of a fluorescently labeled alveolar field on the costal surface of the isolated, perfused rat lung. Surface tension held a saline drop between the objective tip and the lung surface, such that the lung surface was unconstrained. For comparison, we also imaged with O-ring and coverslip; with O-ring, coverslip, and vacuum pressure; and without perfusion. Under each condition, we ventilated the lung and imaged the same region at the endpoints of ventilation. We found use of a coverslip caused a minimal enlargement of the alveolar field; additional use of vacuum pressure caused no further dimensional change; and absence of perfusion did not affect alveolar field dimension. Inflation-induced expansion was unaltered by methodology. In response to inflation, percent expansion was the same as recorded by all four alternative methods. PMID:22074721

  14. Coronectomy of the mandibular third molar: Respect for the inferior alveolar nerve.

    PubMed

    Kouwenberg, A J; Stroy, L P P; Rijt, E D Vree-V D; Mensink, G; Gooris, P J J

    2016-05-01

    The aim of this study was to evaluate the outcomes of coronectomy as an alternative surgical procedure to complete removal of the impacted mandibular third molar in patients with a suspected close relationship between the tooth root(s) and the mandibular canal. A total of 151 patients underwent coronectomy and were followed up with clinical examinations and panoramic radiographs for a minimum of 6 months after surgery. None of the patients exhibited inferior alveolar nerve injury. Eruption of the retained root(s) was more frequent in younger patients (18-35 years). Thirty-six patients (23.8%) exhibited insufficient growth of new bone in the alveolar defect, and 11.3% required a second surgical procedure to remove the root remnant(s). Our results indicate that coronectomy can be a reliable alternative to complete removal of the impacted mandibular third molar in patients exhibiting an increased risk of damage to the inferior alveolar nerve on panoramic radiographs. PMID:26976696

  15. Evaluation of the anaesthetic depth during piglet castration under an automated isoflurane-anaesthesia at farm level.

    PubMed

    Schwennen, Cornelia; Kolbaum, Nina; Waldmann, Karl-Heinz; Höltig, Doris

    2016-01-01

    Piglet castration under isoflurane-anaesthesia could represent an alternative to the practice of castration without anaesthesia. The objective of this study was to evaluate practicality and effectiveness of an automated isoflurane-anaesthesia for castration. A field study on three different farms in Germany (farm A, B: 200 sows; C: 540 sows) was performed. In total, 1429 (1166 anaesthetised and 263 conventionally castrated) male piglets (age: 1-8 days; bodyweight: 0.7-3.7 kg) were monitored. All piglets were treated with nonsteroidal anti-inflammatory drugs directly before castration. Castration and anaesthesia were performed by the farm-manager in presence of a veterinarian. All farmers used the PIGNAP Pro® (Agrosystems GmbH, CH) anaesthetic device (5 vol.% isoflurane, 30% oxygen; flow rate: 2 l/min). Vocalisation and defensive movements of 1166 anaesthetised piglets was rated using a scoring system. Presence or absence of the palpebral- and flexor-reflex was noted. Approximately every second piglet was weighed and oxygen-saturation and pulse- frequency of 231 animals were measured during treatment. Rectal temperatures before and after castration of 264 anaesthetised and 263 conventionally castrated piglets were compared. Only 77% of the anaesthetised piglets showed a sufficient anaesthetic depth based on the assessment of reflexes as well as vocalisations and defensive movements. It was found that the probability for a sufficient depth of anaesthesia decreases with increasing age and weight. The measurements of the pulse-frequency and oxygen-saturation showed an average oxygen-saturation of 98% and an average heart rate of 270/min during anaesthesia. The conventionally castrated piglets had significantly higher rectal temperatures in comparison to the anaesthetised (p < 0.0001). The result of 77% sufficiently anaesthetised piglets is not adequate for commercial application of this technology. PMID:26904895

  16. A comparison of the immunological effects of propofol and isoflurane for maintenance of anesthesia in healthy dogs.

    PubMed

    Tomihari, Mizuki; Nishihara, Akira; Shimada, Terumasa; Yanagawa, Masashi; Miyoshi, Masafumi; Miyahara, Kazurou; Oishi, Akihiro

    2015-10-01

    Most anesthetics have an immuno-suppressive effect on cellular and neurohumoral immunity, and research shows that total intravenous anesthesia (TIVA) with propofol has a greater immuno-protective effect than inhalational anesthesia in human medicine. However, in veterinary clinics, these effects remain ambiguous. To clarify the details, we focused on propofol and isoflurane, investigating clinical blood hematology and immunological profiles drawn from healthy dogs under and after two anesthesia techniques. Twelve healthy adult beagles were included in this study, randomly assigned to the propofol anesthesia group (group P: n=6) or the isoflurane anesthesia group (group I: n=6). In both groups, the number of lymphocytes in peripheral blood decreased after 2 hr of anesthesia (2 hr), but group P showed significantly less decrease than group I. For T-lymphocyte subsets examined by flowcytometry, the ratio of CD3+, CD4+ and CD8+ lymphocytes in the peripheral blood mononuclear cell (PBMC) of group P at 2 hr also exhibited a high level compared to group I. Moreover, for mRNA expression of cytokines measured by real-time PCR, the IL2 (pro-inflammatory cytokine) of group P showed no decrease like group I. The IL10 (anti-inflammatory cytokine) of group P also showed no increase like group I, while both cytokines maintained nearly the same level until 2 hr. These results suggest that, compared to propofol, isoflurane had more strongly immuno-suppression caused by anesthesia, and propofol itself might have some immuno-protective effects. Thus, TIVA with propofol might benefit immunological support in the perioperative period of dogs. PMID:25960120

  17. A comparison of the immunological effects of propofol and isoflurane for maintenance of anesthesia in healthy dogs

    PubMed Central

    TOMIHARI, Mizuki; NISHIHARA, Akira; SHIMADA, Terumasa; YANAGAWA, Masashi; MIYOSHI, Masafumi; MIYAHARA, Kazurou; OISHI, Akihiro

    2015-01-01

    Most anesthetics have an immuno-suppressive effect on cellular and neurohumoral immunity, and research shows that total intravenous anesthesia (TIVA) with propofol has a greater immuno-protective effect than inhalational anesthesia in human medicine. However, in veterinary clinics, these effects remain ambiguous. To clarify the details, we focused on propofol and isoflurane, investigating clinical blood hematology and immunological profiles drawn from healthy dogs under and after two anesthesia techniques. Twelve healthy adult beagles were included in this study, randomly assigned to the propofol anesthesia group (group P: n=6) or the isoflurane anesthesia group (group I: n=6). In both groups, the number of lymphocytes in peripheral blood decreased after 2 hr of anesthesia (2 hr), but group P showed significantly less decrease than group I. For T-lymphocyte subsets examined by flowcytometry, the ratio of CD3+, CD4+ and CD8+ lymphocytes in the peripheral blood mononuclear cell (PBMC) of group P at 2 hr also exhibited a high level compared to group I. Moreover, for mRNA expression of cytokines measured by real-time PCR, the IL2 (pro-inflammatory cytokine) of group P showed no decrease like group I. The IL10 (anti-inflammatory cytokine) of group P also showed no increase like group I, while both cytokines maintained nearly the same level until 2 hr. These results suggest that, compared to propofol, isoflurane had more strongly immuno-suppression caused by anesthesia, and propofol itself might have some immuno-protective effects. Thus, TIVA with propofol might benefit immunological support in the perioperative period of dogs. PMID:25960120

  18. Candidates Cell Sources to Regenerate Alveolar Bone from Oral Tissue

    PubMed Central

    Nishimura, Masahiro; Takase, Kazuma; Suehiro, Fumio; Murata, Hiroshi

    2012-01-01

    Most of the cases of dental implant surgery, especially the bone defect extensively, are essential for alveolar ridge augmentation. As known as cell therapy exerts valuable effects on bone regeneration, numerous reports using various cells from body to regenerate bone have been published, including clinical reports. Mesenchymal cells that have osteogenic activity and have potential to be harvested from intra oral site might be a candidate cells to regenerate alveolar bone, even dentists have not been harvested the cells outside of mouth. This paper presents a summary of somatic cells in edentulous tissues which could subserve alveolar bone regeneration. The candidate tissues that might have differentiation potential as mesenchymal cells for bone regeneration are alveolar bone chip, bone marrow from alveolar bone, periosteal tissue, and gingival tissue. Understanding their phenotype consecutively will provide a rational approach for alveolar ridge augmentation. PMID:22505911

  19. [Alveolar hemorrhage associated with intestinal inflammatory disease and Hashimoto thyroiditis].

    PubMed

    Rabec, C; Barcat, J; Rey, D

    2003-06-01

    Diffuse alveolar hemorrhage (DAH) is characterized by diffuse bleeding into alveolar spaces. Three histopathological patterns may be seen: 1) pulmonary capillaritis due to immunological aggression to the membrane, 2) diffuse alveolar damage within the context of acute respiratory distress syndrome, and 3) and "bland" DAH without alveolar or capillary damage. In the first two groups, pulmonary damage usually occurs within the context of a systemic disease. In the last, injury is usually found only in the lung, an entity called pulmonary hemosiderosis. We present a case of DAH with neither capillaritis nor diffuse alveolar damage in association with inflammatory bowel disease and Hashimoto thyroiditis. The case is interesting both because the association has not yet been described in the literature and because the presence of alveolar bleeding without evident tissue damage within the context of known autoimmune diseases may extend the field to include a new pathophysiological mechanism of pulmonary hemorrhage. PMID:12797945

  20. Record Sea Ice Minimum

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Arctic sea ice reached a record low in September 2007, below the previous record set in 2005 and substantially below the long-term average. This image shows the Arctic as observed by the Advanced Microwave Scanning Radiometer for EOS (AMSR-E) aboard NASA's Aqua satellite on September 16, 2007. In this image, blue indicates open water, white indicates high sea ice concentration, and turquoise indicates loosely packed sea ice. The black circle at the North Pole results from an absence of data as the satellite does not make observations that far north. Three contour lines appear on this image. The red line is the 2007 minimum, as of September 15, about the same time the record low was reached, and it almost exactly fits the sea ice observed by AMSR-E. The green line indicates the 2005 minimum, the previous record low. The yellow line indicates the median minimum from 1979 to 2000.

  1. Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats

    PubMed Central

    Cissé, Youssouf; Inoue, Isao; Kido, Hiroshi

    2012-01-01

    Background Oseltamivir phosphate (OP, Tamiflu®) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9°C to 41°C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia. Objective The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza-associated encephalopathy. Methods Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 × 105 plaque forming unit in PBS, 60 µL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane-anesthetized IAV-infected rats during hyperthermia. Results We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40°C in OP non-administered rats, appeared at 38°C core temperature. Atropine (30 mg/kg) blocked the theta oscillations. Conclusion Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature.

  2. Recent advances in alveolar biology: some new looks at the alveolar interface.

    PubMed

    Possmayer, Fred; Hall, Stephen B; Haller, Thomas; Petersen, Nils O; Zuo, Yi Y; Bernardino de la Serna, Jorge; Postle, Anthony D; Veldhuizen, Ruud A W; Orgeig, Sandra

    2010-08-31

    This article examines the manner in which some new methodologies and novel concepts have contributed to our understanding of how pulmonary surfactant reduces alveolar surface tension. Investigations utilizing small angle X-ray diffraction, inverted interface fluorescence microscopy, time of flight-secondary ion mass spectroscopy, atomic force microscopy, two-photon fluorescence microscopy and electrospray mass spectroscopy are highlighted and a new model of ventilation-induced acute lung injury described. This contribution attempts to emphasize how these new approaches have resulted in a fuller appreciation of events presumably occurring at the alveolar interface. PMID:20206718

  3. Isolation and Culture of Human Alveolar Type II Pneumocytes.

    PubMed

    Witherden, I R; Tetley, T D

    2001-01-01

    Alveolar type II pneumocytes (alveolar type II cells; TII cells) play an important role in the homeostasis of the alveolar unit. They are the progenitor cells to the type I pneumocyte and are therefore responsible for regeneration of alveolar epithelium following alveolar epithelial cell damage. The type I cell covers over 90% of the alveolar surface, reflecting its capacity to stretch into a flattened cell with very little depth (approx. 0.1 µm), but with a large surface area, to facilitate gas exchange. Nevertheless, the type II cell outnumbers type I cells, estimated to be by 2:1 in rodents. Most of the type II cell lies buried in the interstitium of the alveolus, with only the apical tip of the cell reaching into the airspace, through which another crucial function, provision of alveolar surfactant, occurs. Surfactant synthesis and secretion is a unique feature of type II cells; surfactant consists of a high proportion of phospholipids (approx. 90%) and a small proportion of protein (approx. 10%), which contains surfactant apoprotein (SP), of which four have so far been described, SP-A, SP-B, SP-C, and SP-D (1,2). Surfactant is highly surface active and is essential to prevent alveolar collapse. In addition, surfactant has many other roles, including pulmonary host defense. Compromised surfactant synthesis and function are believed to be a feature of numerous disease states (1,2), including infant respiratory distress syndrome, adult respiratory distress syndrome, alveolar proteinosis, and microbial infection. PMID:21336897

  4. Minimum variance geographic sampling

    NASA Technical Reports Server (NTRS)

    Terrell, G. R. (Principal Investigator)

    1980-01-01

    Resource inventories require samples with geographical scatter, sometimes not as widely spaced as would be hoped. A simple model of correlation over distances is used to create a minimum variance unbiased estimate population means. The fitting procedure is illustrated from data used to estimate Missouri corn acreage.

  5. Minimum Critical Values Study

    SciTech Connect

    Fox, P.B.

    2005-07-11

    This report provides minimum critical values for various 30-cm water-reflected uranium and plutonium oxide and nitrate aqueous mixtures as calculated by the SCALE CSAS1X sequence using the 238-group ENDF/B-V neutron cross-section library. The minimum values were determined through parametric searches in one-dimensional geometry. The calculations have been performed to obtain the minimum values: critical volume and mass for spheres, critical radius for cylinders, critical thickness for slabs, and minimum critical concentration (infinite geometry) for the following homogeneous mixtures: (1) UO{sub 2}-H{sub 2}O for 3, 4, 5, 20, and 100 wt % {sup 235}U; (2) UNH for 3, 4, 5, 20, and 100 wt % {sup 235}U; (3) PuO{sub 2}-H{sub 2}O for 100/0/0, 95/5/0, 90/5/5, 80/10/10, and 71/17/11/1 wt % of {sup 239}Pu/{sup 240}Pu/{sup 241}Pu(/{sup 242}Pu); and (4) PuNH for 100/0/0, 95/5/0, 90/5/5, 80/10/10, and 71/17/11/1 wt % of {sup 239}Pu/{sup 240}Pu/{sup 241}Pu(/{sup 242}Pu). All bounding surfaces were fully reflected by 30 cm of H{sub 2}O.

  6. Comparison of remifentanil versus regional anaesthesia in children anaesthetised with isoflurane/nitrous oxide. International Remifentanil Paediatric Anaesthesia Study group.

    PubMed

    Prys-Roberts, C; Lerman, J; Murat, I; Taivainen, T; Lopez, T; Lejus, C; Spahr-Schopfer, I; Splinter, W; Kirkham, A J

    2000-09-01

    We compared the efficacy and safety of a remifentanil (0.25 microg x kg(-1) x min(-1)-based balanced anaesthetic technique with a bupivacaine-based regional anaesthetic technique in an open label, multicentre study in 271 ASA physical status 1 or 2 children aged 1-12 years. Subjects requiring major intra-abdominal, urological or orthopaedic surgery were randomly allocated to receive either intravenous remifentanil (group R; n = 185) or epidural bupivacaine (group B; n = 86) with isoflurane/nitrous oxide for their anaesthesia. The majority of children in both groups (85% in group R, 78% in group B) showed no defined response to skin incision, and although the mean increase in systolic blood pressure (+11 mm Hg) was significantly greater in group R than in group B, this change did not represent a serious haemodynamic disturbance. More children in group R (31%) required interventions to treat hypotension and/or bradycardia than those in group B (12%), but these were easily managed by administration of fluids or anticholinergic drugs. Adverse events, mainly nausea and/or vomiting, occurred in 45% of group R and 42% of group B (NS). The adverse event profile of remifentanil in this study was typical of a potent mu-opioid receptor agonist. Remifentanil was as effective as epidural or caudal block in providing analgesia and suppressing physiological responses to surgical stimuli in children aged between 1 and 12 years undergoing major abdominal, urological, or orthopaedic surgery under isoflurane/nitrous oxide anaesthesia. PMID:10947750

  7. Brief anesthesia by isoflurane alters plasma corticosterone levels distinctly in male and female rats: Implications for tissue collection methods.

    PubMed

    Bekhbat, Mandakh; Merrill, Liana; Kelly, Sean D; Lee, Vanessa K; Neigh, Gretchen N

    2016-05-15

    Euthanasia by anesthetic agents is commonly performed prior to tissue collection in order to minimize pain and distress to the animal. However, depending on their mechanism of action as well as administration regimen, different methods of anesthesia may trigger an acute stress response through engaging the hypothalamic-pituitary-adrenal (HPA) axis, which can impact numerous other physiological processes that the researcher may wish to examine as endpoints. We investigated the effects of the commonly used anesthetic agent isoflurane on two different endpoints related to the stress response: plasma corticosterone levels and gene expression of the glucocorticoid receptor (GR) as well as several of its regulators including FK506-binding protein 51 (Fkbp5) in the hippocampus of male and female rats. Our results indicate that brief exposure to anesthesia by isoflurane prior to decapitation can alter plasma corticosterone levels differentially in male and female rats within minutes without impacting gene expression in the hippocampus. We conclude that collection methods can influence stress-related physiological endpoints in female rats and the potential influence of even brief anesthesia as well as sex differences in response to anesthesia should be evaluated during the experimental design process and data interpretation. This finding is particularly important in light of new NIH standards regarding sex and reproducibility, and care should be taken to be certain that sex differences in endpoints of interest are not an artifact of sex differences in response to collection paradigms. PMID:26946276

  8. Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1β elevation and the resultant cognitive deficits in aged rats

    SciTech Connect

    Li, Zheng-Qian; Rong, Xiao-Ying; Liu, Ya-Jie; Ni, Cheng; Tian, Xiao-Sheng; Mo, Na; Chui, De-Hua; Guo, Xiang-Yang

    2013-09-06

    Highlights: •Isoflurane induces hippocampal IL-1β elevation and cognitive deficits in aged rats. •Isoflurane transiently activates the canonical NF-κB pathway in aged rat hippocampus. •NF-κB inhibitor mitigates isoflurane-induced IL-1β elevation and cognitive deficits. •We report a linkage between NF-κB signaling, IL-1β expression, and cognitive changes. -- Abstract: Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1β levels and anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6 h after isoflurane exposure and hippocampal IL-1β elevation from 1 to 6 h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1β increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1β, partially via activation of the canonical NF-κB pathway, in aged rats.

  9. An estimation of mechanical stress on alveolar walls during repetitive alveolar reopening and closure.

    PubMed

    Chen, Zheng-Long; Song, Yuan-Lin; Hu, Zhao-Yan; Zhang, Su; Chen, Ya-Zhu

    2015-08-01

    Alveolar overdistension and mechanical stresses generated by repetitive opening and closing of small airways and alveoli have been widely recognized as two primary mechanistic factors that may contribute to the development of ventilator-induced lung injury. A long-duration exposure of alveolar epithelial cells to even small, shear stresses could lead to the changes in cytoskeleton and the production of inflammatory mediators. In this paper, we have made an attempt to estimate in situ the magnitudes of mechanical stresses exerted on the alveolar walls during repetitive alveolar reopening by using a tape-peeling model of McEwan and Taylor (35). To this end, we first speculate the possible ranges of capillary number (Ca) ≡ μU/γ (a dimensionless combination of surface tension γ, fluid viscosity μ, and alveolar opening velocity U) during in vivo alveolar opening. Subsequent calculations show that increasing respiratory rate or inflation rate serves to increase the values of mechanical stresses. For a normal lung, the predicted maximum shear stresses are <15 dyn/cm(2) at all respiratory rates, whereas for a lung with elevated surface tension or viscosity, the maximum shear stress will notably increase, even at a slow respiratory rate. Similarly, the increased pressure gradients in the case of elevated surface or viscosity may lead to a pressure drop >300 dyn/cm(2) across a cell, possibly inducing epithelial hydraulic cracks. In addition, we have conceived of a geometrical model of alveolar opening to make a prediction of the positive end-expiratory pressure (PEEP) required to splint open a collapsed alveolus, which as shown by our results, covers a wide range of pressures, from several centimeters to dozens of centimeters of water, strongly depending on the underlying pulmonary conditions. The establishment of adequate regional ventilation-to-perfusion ratios may prevent recruited alveoli from reabsorption atelectasis and accordingly, reduce the required levels of

  10. Pulmonary alveolar proteinosis in a marble worker.

    PubMed

    Yildirim, Berna Botan; Akgedik, Recep; Akgedik, Sukran; Nazaroglu, Hasan

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rarely seen disease of the alveoli, characterized by accumulation of proteinous material, which stains positive with periodic acid Schiff, in the alveoli. Secondary PAP may develop as a result of occupational exposure to materials such as silica and indium. In the paper, together with a review of the relevant literature, we present an uncommon case of a 47-year old male, marble worker who was diagnosed with PAP associated with a 12-year history of exposure to marble dust. Int J Occup Med Environ Health 2016;29(5):871-876. PMID:27518894

  11. Daily Isoflurane Exposure Increases Barbiturate Insensitivity in Medullary Respiratory and Cortical Neurons via Expression of ε-Subunit Containing GABA ARs

    PubMed Central

    Hengen, Keith B.; Nelson, Nathan R.; Stang, Kyle M.; Johnson, Stephen M.; Smith, Stephanie M.; Watters, Jyoti J.; Mitchell, Gordon S.; Behan, Mary

    2015-01-01

    The parameters governing GABAA receptor subtype expression patterns are not well understood, although significant shifts in subunit expression may support key physiological events. For example, the respiratory control network in pregnant rats becomes relatively insensitive to barbiturates due to increased expression of ε-subunit-containing GABAARs in the ventral respiratory column. We hypothesized that this plasticity may be a compensatory response to a chronic increase in inhibitory tone caused by increased central neurosteroid levels. Thus, we tested whether increased inhibitory tone was sufficient to induce ε-subunit upregulation on respiratory and cortical neurons in adult rats. Chronic intermittent increases in inhibitory tone in male and female rats was induced via daily 5-min exposures to 3% isoflurane. After 7d of treatment, phrenic burst frequency was less sensitive to barbiturate in isoflurane-treated male and female rats in vivo. Neurons in the ventral respiratory group and cortex were less sensitive to pentobarbital in vitro following 7d and 30d of intermittent isoflurane-exposure in both male and female rats. The pentobarbital insensitivity in 7d isoflurane-treated rats was reversible after another 7d. We hypothesize that increased inhibitory tone in the respiratory control network and cortex causes a compensatory increase in ε-subunit-containing GABAARs. PMID:25748028

  12. Rising above the Minimum Wage.

    ERIC Educational Resources Information Center

    Even, William; Macpherson, David

    An in-depth analysis was made of how quickly most people move up the wage scale from minimum wage, what factors influence their progress, and how minimum wage increases affect wage growth above the minimum. Very few workers remain at the minimum wage over the long run, according to this study of data drawn from the 1977-78 May Current Population…

  13. Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

    PubMed Central

    Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

    2013-01-01

    Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival soft tissue and alveolar bone following tooth extraction. For target identification and validation, hard and soft tissue were extracted from mini-pigs at the indicated times after tooth extraction. From triplicate experiments, 56 proteins in soft tissue and 27 proteins in alveolar bone were found to be differentially expressed before and after tooth extraction. The expression of 21 of those proteins was altered in both soft tissue and bone. Comparison of the activated networks in soft tissue and alveolar bone highlighted their distinct responsibilities in bone and tissue healing. Moreover, we found that there is crosstalk between identified proteins in soft tissue and alveolar bone with respect to cellular assembly, organization, and communication. Among these proteins, we examined in detail the expression patterns and associated networks of ATP5B and fibronectin 1. ATP5B is involved in nucleic acid metabolism, small molecule biochemistry, and neurological disease, and fibronectin 1 is involved in cellular assembly, organization, and maintenance. Collectively, our findings indicate that bone regeneration is accompanied by a profound interaction among networks regulating cellular resources, and they provide novel insight into the molecular mechanisms involved in the healing of periodontal tissue after tooth extraction. PMID:23824910

  14. Alveolar Epithelial Dynamics in Post-pneumonectomy Lung Growth

    PubMed Central

    Chamoto, Kenji; Gibney, Barry C.; Ackermann, Maximilian; Lee, Grace S.; Konerding, Moritz A.; Tsuda, Akira; Mentzer, Steven J.

    2013-01-01

    The intimate anatomic and functional relationship between epithelial cells and endothelial cells within the alveolus suggests the likelihood of a coordinated response during post-pneumonectomy lung growth. To define the population dynamics and potential contribution of alveolar epithelial cells to alveolar angiogenesis, we studied alveolar Type II and Type I cells during the 21 days after pneumonectomy. Alveolar Type II cells were defined and isolated by flow cytometry using a CD45−, MHC class II+, phosphine+ phenotype. These phenotypically defined alveolar Type II cells demonstrated an increase in cell number after pneumonectomy; the increase in cell number preceded the increase in Type I (T1α+) cells. Using a parabiotic wild type/GFP pneumonectomy model, less than 3% of the Type II cells and 1% of the Type I cells were positive for GFP—a finding consistent with the absence of a blood-borne contribution to alveolar epithelial cells. The CD45−, MHC class II+, phosphine+ Type II cells demonstrated the active transcription of angiogenesis-related genes both before and after pneumonectomy. When the Type II cells on day 7 after pneumonectomy were compared to non-surgical controls, 10 genes demonstrated significantly increased expression (p<.05). In contrast to the normal adult Type II cells, there was notable expression of inflammation-associated genes (Ccl2, Cxcl2, Ifng) as well as genes associated with epithelial growth (Ereg, Lep). Together, the data suggest an active contribution of local alveolar Type II cells to alveolar growth. PMID:23408540

  15. Diffuse alveolar haemorrhage associated with aerosol propellant use

    PubMed Central

    Kelchen, Phillip; Jamous, Fady; Huntington, Mark K

    2013-01-01

    Diffuse alveolar haemorrhage (DAH) is a clinical syndrome resulting from injury to the alveolar microcirculation, most commonly associated with not only autoimmune disorders or connective tissue disease, but also a variety of infections, neoplasms and toxins. We report here a case of an otherwise healthy young man with DAH attributable to an inhalation injury resulting from use of aerosol spray paint. PMID:23955981

  16. Correction of alveolar cleft with calcium-based bone substitutes.

    PubMed

    Lazarou, Spiros A; Contodimos, George B; Gkegkes, Ioannis D

    2011-05-01

    The criterion standard of alveolar cleft repair is iliac crest bone graft before secondary canine eruption. Tooth eruption has never been shown to occur in synthetic bone substitute, and there is no ideal autologous bone graft for primary repair. This prospective study evaluated alveolar cleft grafting with a calcium substitute before primary canine eruption. Ten consecutive patients with complete cleft lip, palate, and unilateral alveolar cleft with reasonably aligned arches were grafted beginning in January 2003 to March 2007. Mean age at surgery was 10.4 months. Follow-up ranged from 3 to 7 years. Radiologic evaluation of alveolar ridge was performed at the age of 4.All 10 patients were operated on by the same surgeon using the same technique, that is, conservative elevation of nasal, oral, and anterior alveolar mucosal flaps around the cleft, closure of nasal and oral flaps, placement of 1 to 3 mL of calcium substitute paste or crystals in the pocket, and closure of the anterior alveolar mucosa. All 10 patients healed without complication. Clinical evaluation revealed a well-healed arch with primary canine growth in the area of the previous cleft. Adequate normal bone formation and often a descending secondary canine were radiologically confirmed. Calcium substitutes offer significant advantages over other biomaterials as well as autologous bone grafts particularly in the primary alveolar cleft reconstruction. Our study has shown for the first time that teeth can erupt through this material, which turns into a normal functioning bone in the alveolar ridge. PMID:21558929

  17. Tongue-Palate Contact of Perceptually Acceptable Alveolar Stops

    ERIC Educational Resources Information Center

    Lee, Alice; Gibbon, Fiona E.; O'Donovan, Cliona

    2013-01-01

    Increased tongue-palate contact for perceptually acceptable alveolar stops has been observed in children with speech sound disorders (SSD). This is a retrospective study that further investigated this issue by using quantitative measures to compare the target alveolar stops /t/, /d/ and /n/ produced in words by nine children with SSD (20 tokens of…

  18. Unexplained alveolar hemorrhage associated with Ginkgo and ginseng use.

    PubMed

    Carlile, Paul V

    2015-04-01

    The author presents a case of diffuse alveolar hemorrhage in a woman consuming Ginkgo biloba extract and ginseng. The patient had no illnesses or exposures that would predispose to diffuse alveolar hemorrhage, and an extensive evaluation revealed no etiology. The patient has had no further bleeding since discontinuing Ginkgo biloba extract and ginseng 1 year ago. PMID:25887018

  19. Modulation of γ-Aminobutyric Acid Type A Receptor-mediated Spontaneous Inhibitory Postsynaptic Currents in Auditory Cortex by Midazolam and Isoflurane

    PubMed Central

    Verbny, Yakov I.; Merriam, Elliott B.; Banks, Matthew I.

    2006-01-01

    Background Anesthetic agents that target γ-aminobutyric acid type A (GABAA) receptors modulate cortical auditory evoked responses in vivo, but the cellular targets involved are unidentified. Also, for agents with multiple protein targets, the relative contribution of modulation of GABAA receptors to effects on cortical physiology is unclear. The authors compared effects of the GABAA receptor-specific drug midazolam with the volatile anesthetic isoflurane on spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal cells of auditory cortex. Methods Whole cell recordings were obtained in murine brain slices at 34°C. GABAA sIPSCs were isolated by blocking ionotropic glutamate receptors. Effects of midazolam and isoflurane on time course, amplitude, and frequency of sIPSCs were measured. Results The authors detected no effect of midazolam at 0.01 μM on sIPSCs, whereas midazolam at 0.1 and 1 μM prolonged the decay of sIPSCs by approximately 25 and 70%, respectively. Isoflurane at 0.1, 0.25, and 0.5 mM prolonged sIPSCs by approximately 45, 150, and 240%, respectively. No drug-specific effects were observed on rise time or frequency of sIPSCs. Isoflurane at 0.5 mM caused a significant decrease in sIPSC amplitude. Conclusions The dose dependence of isoflurane effects on GABAA sIPSCs in pyramidal cells is consistent with effects on auditory evoked response in vivo. By contrast, comparable effects of midazolam on GABAA sIPSCs arise at concentrations exceeding those currently thought to be achieved in vivo, suggesting that the cellular targets of midazolam reside elsewhere in the thalamocortical circuit or that the concentration of midazolam reached in the brain is higher than currently believed. PMID:15851883

  20. Cocaine-induced Fos expression is detectable in the frontal cortex and striatum of rats under isoflurane but not α-chloralose anesthesia: implications for FMRI

    PubMed Central

    Kufahl, Peter R.; Pentkowski, Nathan S.; Heintzelman, Krista; Neisewander, Janet L.

    2009-01-01

    The ability of intravenous cocaine to induce Fos protein expression in anesthetized rats was tested. Two anesthetic regimens commonly used for in vivo FMRI of animals, i.v. α-chloralose and gaseous isoflurane, were studied in separate cohorts. The first experiment included three groups that received the following treatments: saline i.v. and no anesthetic; 2 mg/kg cocaine i.v. and no anesthetic; and 2 mg/kg cocaine i.v. under 36 mg/kg/h α-chloralose anesthesia. The second experiment had a factorial design of four groups that were either nonanesthetized or isoflurane-treated and were either given saline or cocaine (2 mg/kg, i.v.). Anesthetized rats were maintained for 2 h under 2.5–3.5% isoflurane anesthesia, while nonanesthetized rats were kept in an alternative environment for the same time period. Rats were given 2 mg/kg cocaine or saline i.v., 30 min into the test session. Rats were perfused and their brains were processed for Fos immunohistochemistry 90 min after the i.v. treatment. In both experiments, the frontal cortex and striatum of the cocaine-treated nonanesthetized rats expressed Fos in greater amounts than the saline-treated nonanesthetized rats, as expected. The α-chloralose treatment prevented cocaine-induced Fos expression across all eight subregions of the striatum and frontal cortex that were examined. In contrast, isoflurane only partially attenuated Fos expression in the orbital and Cg2 subregions of frontal cortex. These results suggest a strong advantage for using isoflurane, as opposed to α-chloralose, when studying anesthetized rats for in vivo effects of psychostimulants. PMID:19467261

  1. Cocaine-induced Fos expression is detectable in the frontal cortex and striatum of rats under isoflurane but not alpha-chloralose anesthesia: implications for FMRI.

    PubMed

    Kufahl, Peter R; Pentkowski, Nathan S; Heintzelman, Krista; Neisewander, Janet L

    2009-07-30

    The ability of intravenous cocaine to induce Fos protein expression in anesthetized rats was tested. Two anesthetic regimens commonly used for in vivo FMRI of animals, i.v. alpha-chloralose and gaseous isoflurane, were studied in separate cohorts. The first experiment included three groups that received the following treatments: saline i.v. and no anesthetic; 2 mg/kg cocaine i.v. and no anesthetic; and 2mg/kg cocaine i.v. under 36 mg/kg/h alpha-chloralose anesthesia. The second experiment had a factorial design of four groups that were either nonanesthetized or isoflurane-treated and were either given saline or cocaine (2 mg/kg, i.v.). Anesthetized rats were maintained for 2 h under 2.5-3.5% isoflurane anesthesia, while nonanesthetized rats were kept in an alternative environment for the same time period. Rats were given 2 mg/kg cocaine or saline i.v., 30 min into the test session. Rats were perfused and their brains were processed for Fos immunohistochemistry 90 min after the i.v. treatment. In both experiments, the frontal cortex and striatum of the cocaine-treated nonanesthetized rats expressed Fos in greater amounts than the saline-treated nonanesthetized rats, as expected. The alpha-chloralose treatment prevented cocaine-induced Fos expression across all eight subregions of the striatum and frontal cortex that were examined. In contrast, isoflurane only partially attenuated Fos expression in the orbital and Cg2 subregions of frontal cortex. These results suggest a strong advantage for using isoflurane, as opposed to alpha-chloralose, when studying anesthetized rats for in vivo effects of psychostimulants. PMID:19467261

  2. Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia.

    PubMed

    Nanjappa, Sowmya; Jeong, Daniel K; Muddaraju, Manjunath; Jeong, Katherine; Hill, Ebone D; Greene, John N

    2016-07-01

    Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying infection, coagulopathy, and the frequent use of anticoagulants, given the high incidence of venous thrombosis in this population. Dyspnea, fever, and cough are commonly presenting symptoms. However, clinical manifestations can be variable. Obvious bleeding (hemoptysis) is not always present and can pose a potential diagnostic challenge. Without prompt treatment, hypoxia that rapidly progresses to respiratory failure can occur. Diagnosis is primarily based on radiological and bronchoscopic findings. This syndrome is especially common in patients with hematological malignancies, given an even greater propensity for thrombocytopenia as a result of bone marrow suppression as well as the often prolonged immunosuppression in this patient population. The syndrome also has an increased incidence in individuals with hematological malignancies who have received a bone marrow transplant. We present a case series of 5 patients with acute myeloid leukemia presenting with diffuse alveolar hemorrhage at our institution. A comparison of clinical manifestations, radiographic findings, treatment course, and outcomes are described. A review of the literature and general overview of the diagnostic evaluation, differential diagnoses, pathophysiology, and treatment of this syndrome are discussed. PMID:27556667

  3. Biology of alveolar type II cells.

    PubMed

    Mason, Robert J

    2006-01-01

    The purpose of this review is to highlight the many metabolic properties of alveolar type II cells, their production of surfactant, their role in innate immunity, and their importance in the repair process after lung injury. The review is based on the medical literature and results from our laboratory. Type II cells produce and secrete pulmonary surfactant and for that purpose they need to synthesize the lipids of surfactant. One of the regulators of lipogenesis is the transcription factor sterol regulatory element binding protein-1c (SREBP-1c). This is a key transcription factor regulating fatty acid synthesis. Type II cells also proliferate to restore the epithelium after lung injury, clear alveolar fluid by transporting sodium from the apical to the basolateral surface, and participate in the innate immune response to inhaled materials and organisms. The type II cell is, in many ways, the defender of the alveolus. However, the type II cells work in concert with the other cells in the gas exchange regions of the lung to keep the alveoli open and reduce inflammation due to irritants in the air we breathe. PMID:16423262

  4. Effects of immunopotentiating agents on alveolar macrophage properties.

    PubMed

    Charley, B

    1986-01-01

    Infectious respiratory diseases in man and in domestic animals are characterized by the presence of a large number of different microorganisms: viruses, bacterias, mycoplasmas. It is therefore necessary to stimulate non-specific defense mechanisms in the lung and especially alveolar macrophages (AM). These cells, located in the alveolar air-spaces, play a major role in the lung clearance mechanisms and exert antibacterial, antiviral and antitumoral activities. Activation of alveolar macrophages was studied in vitro with lipopolysaccharide (LPS), lymphokines or mycobacterial derivatives (MDP). Rodent alveolar macrophages were rendered cytotoxic by in vitro exposure to LPS, free MDP or liposome-encapsulated MDP derivatives. In vivo, intravenously administered liposomes containing lipophilic MDP derivatives induced cytotoxic alveolar macrophages and protected mice against the development of pulmonary metastases. PMID:3539492

  5. Relative effects of asbestos and wollastonite on alveolar macrophages

    SciTech Connect

    Pailes, W.H.; Judy, D.J.; Resnick, H.; Castranova, V.

    1984-01-01

    Rabbit alveolar macrophages were exposed in culture to chrysotile asbestos, wollastonite, or latex, and the effects on various biochemical and physiological parameters related to cellular viability and fibrogenicity were determined. Exposure of alveolar macrophages to asbestos, wollastonite, or latex for 3 d has no effect on oxygen consumption or cellular volume. However, treatment of alveolar macrophages with as little as 25 ..mu..g asbestos/ml for 1 d increases lysosomal enzyme release and decreases membrane integrity, i.e., decreases trypan blue exclusion and increases leakage of cytosolic enzymes. In contrast, exposure of alveolar macrophages to wollastonite or latex at 250 ..mu..g/ml does not induce lysosomal enzyme release or alter membrane integrity even after 3 d of exposure in culture. These data suggest that chrysotile asbestos damages rabbit alveolar macrophages, while wollastonite, a potential substitute for asbestos, is far less cyctotoxic. 35 references, 8 figures.

  6. Secondary alveolar bone grafting: our experience with olecranon bone graft.

    PubMed

    Nadal, Emmanuela; Sabás, Mariana; Dogliotti, Pedro; Espósito, Raquel

    2010-03-01

    Management of alveolar cleft has dramatically changed during the last century: secondary alveolar bone grafting is now an integral part of cleft palate and craniofacial center's protocols. The objectives of alveolar repair and bone grafting are as follows: providing a continuous and stable maxillary dental arch, closure of oronasal fistulae, adequate bone for tooth eruption or orthodontic movement, and nasal base support, improving facial aesthetic. Although cancellous iliac bone is the donor site selected more frequently, bone grafts harvested from different sites have been advocated to decrease donor site morbidity.The aim of this study was to propose and evaluate the use of olecranon as a donor site in 24 patients with secondary alveolar cleft. The graft is taken as a single piece to fit the alveolar cleft defect, and it includes periosteum and corticocancellous bone to improve early vascularization and greater volume maintenance. PMID:20186086

  7. Effects of different concentration and duration time of isoflurane on acute and long-term neurocognitve function of young adult C57BL/6 mouse

    PubMed Central

    Liu, Jianhui; Wang, Peijun; Zhang, Xiaoqing; Zhang, Wei; Gu, Guojun

    2014-01-01

    Postoperative cognitive dysfunction (POCD) is a decline in cognitive performance after a surgery with anaesthesia. The exact reasons of surgery and/or anaesthesia resulting in POCD are unclear. The aim of this study is to investigate the effects of different concentration and duration time of isoflurane anaesthesia on cognitive performance and cellular mechanisms involved in learning and memory function. In present work, young adult male C57BL/6 mice (age: 8 weeks) were anaesthetized by different concentration isoflurane in 100% oxygen for different duration time (Mice in group I1 received 0.7% isoflurane 0.5 h, mice in I2 received 0.7% isoflurane 2 h, mice in I3 received 1.4% isoflurane 2 h, and mice in I4 received 1.4% isoflurane 4 h). Non-anaesthetized mice served as control group (I0). Spatial learning was assessed at 10 days post-anesthesia in Morris water maze (MWM). Hippocampal protein expressions of activated caspase 3, NMDA receptor subunit NR2B, and extracellular-signal regulated kinase (ERK) 1/2 were evaluated 24 hours and 2 weeks post anesthesia. Protein expression of activated caspase3 was detected acute elevated in I3 (24 h post-anesthesia) and acute and long-term elevated in I4 (24 hours and 2 weeks post-anesthesia). There was no significant difference between I1, I2 and control group. Protein expressions of NR2B showed an acute and long-term increasement in I1 and I2, decreasement in I4, and an acute decline, then returned to normal in I3 compared to control group. The ratio of phosopho-ERK1/2 to total-ERK showed an acute increasement in I1 and I2, then came to normal 2 weeks post anesthesia compared to control group, meanwhile, we detected an acute and long-term decline in I3 and I4. In MWM test, mice in I1 and I2 showed cognitive improvement, mice in I3 showed similar to control group, while mice in I4 demonstrated cognitive impairment, which were approximately corresponding to the changes of protein expression of NR2B and activation of ERK1

  8. EFFECTS OF PAMIDRONATE ON HUMAN ALVEOLAR OSTEOBLASTS IN VITRO

    PubMed Central

    Marolt, Darja; Cozin, Matthew; Vunjak-Novakovic, Gordana; Cremers, Serge; Landesberg, Regina

    2011-01-01

    Purpose Administration of bisphosphonates has recently been associated with the development of osteonecrotic lesions of the jaw (ONJ). To elucidate the potential contributions of osteogenic cells to the development and regeneration of ONJ, we have isolated primary cells from human alveolar and long/iliac bones, and examined the effects of pamidronate on cell viability, proliferation, osteogenesis and wound healing. Materials and Methods Primary human osteoblasts and bone marrow stromal cells were isolated from alveolar and iliac/long bone and marrow tissue. Cellular proliferation, alkaline phosphatase activity, apoptosis (TUNEL, Caspase-3, and DAPI assays) and wound healing in an in vitro scratch assay were assessed after exposure to pamidronate at a range of clinically relevant doses. Results Primary alveolar osteoblasts proliferated at significantly higher rates than long/iliac bone osteoblasts in vitro. Upon exposure of alveolar osteoblasts and long/iliac bone marrow stromal cells to pamidronate for more than 72h, we have observed significantly decreased cell viability, proliferation, osteogenesis and in vitro wound healing at ≥6 × 10−5 M pamidronate, with the induction of apoptosis in ~20% of cell population. Conclusions The remodeling activity of alveolar bone, indicated by higher proliferation of alveolar osteoblasts, could be negatively affected by exposure to high concentrations of pamidronate over extended periods of time. The absence of anabolic effects of pamidronate on alveolar osteoblasts, and induction of apoptosis in osteogenic cells could negatively affect bone balance at this site, and contribute to osteonecrosis of the jaw. PMID:21856057

  9. Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function

    PubMed Central

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A.; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M.; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin

    2012-01-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness. PMID:23027535

  10. Modern therapy for severe alveolar ridge atrophy.

    PubMed

    Chen, Yu-Feng; Pan, Chin-Yun; Wang, Wen-Chen; Lan, Ting-Hsun

    2013-01-01

    This clinical report illustrates a modern method for oral rehabilitation of severe edentulous atrophic ridge. Shallow vestibule and small denture-bearing area of the maxilla provide insufficient retention, and only the symphyseal region of the mandible has obvious alveolar ridge. The surgery of deepening vestibule of the maxilla ridge was done by using tentative miniscrew combined with old denture and soft liner. The osseointegrated dental implants were installed over symphyseal region of the mandible to act as retentive devices for prostheses. In addition, functional reline with rebase material to build buccal-tongue contact over the retromolar area after denture delivery obtained high satisfaction from the patient. Many clinical conditions cannot be managed solely with implants or preprosthetic surgery alone, whereas a combination of the 2 can achieve successful outcome. PMID:24036818

  11. Epidemiology of human alveolar echinococcosis in China.

    PubMed

    Craig, Philip S

    2006-01-01

    Globally human alveolar echinococcosis (AE) is a rare zoonotic helminthic disease confined to the Northern Hemisphere as sporadic infections in rural populations, principally in some areas of North America, west-central Europe, the Near East, Siberia, Central Asia, Japan and China. In China the first human cases were reported from western regions in the 1960s, but most hospital records remain fragmented and inadequate. From the mid-1990s mass screening surveys using portable ultrasound scanners recorded higher prevalences (up to 6% by county) than in any other areas of the world with some village rates as high as 15%. Risk factors identified for AE cases included ethnicity, sex, age and occupation. The role of the dog in transmission of Echinococcus multilocularis to humans now appears to be significant and may be one of the most important risk factor, in combination with landscape/land-use features conducive to maintaining wildlife host populations. PMID:16338167

  12. Diffuse alveolar damage associated with pulmonary thromboembolism

    PubMed Central

    Kinoshita, Yoshiaki; Sakamoto, Atsuhiko; Koga, Takaomi; Hidaka, Kouko

    2013-01-01

    In contrast to other internal organs, pulmonary arterial hypoperfusion does not always show ischemic changes in the lung parenchyma. Pulmonary thromboembolism (PTE)-related lung injury is extremely rare except in the case of pulmonary infarctions, in which PTE occasionally causes necrosis of the parenchyma. We describe the case of an 86-year-old woman who presented with respiratory failure and bilateral ground-glass opacity predominantly the upper lobes. Autopsy revealed a saddle-shaped old organized thrombi in the main pulmonary artery, relatively fresh thrombi in both pulmonary arteries, and localized diffuse alveolar damage (DAD) in the bilateral upper lung fields. The hypoperfused regions resulting from the thromboembolism anatomically coincided with the pulmonary lesion where DAD was identified. Although PTE is not regarded as a causal factor of DAD, it might induce DAD as a result of hypoperfusion in limited cases. PMID:26029610

  13. Molecular and Integrative Physiological Effects of Isoflurane Anesthesia: The Paradigm of Cardiovascular Studies in Rodents using Magnetic Resonance Imaging

    PubMed Central

    Constantinides, Christakis; Murphy, Kathy

    2016-01-01

    To-this-date, the exact molecular, cellular, and integrative physiological mechanisms of anesthesia remain largely unknown. Published evidence indicates that anesthetic effects are multifocal and occur in a time-dependent and coordinated manner, mediated via central, local, and peripheral pathways. Their effects can be modulated by a range of variables, and their elicited end-effect on the integrative physiological response is highly variable. This review summarizes the major cellular and molecular sites of anesthetic action with a focus on the paradigm of isoflurane (ISO) – the most commonly used anesthetic nowadays – and its use in prolonged in vivo rodent studies using imaging modalities, such as magnetic resonance imaging (MRI). It also presents established evidence for normal ranges of global and regional physiological cardiac function under ISO, proposes optimal, practical methodologies relevant to the use of anesthetic protocols for MRI and outlines the beneficial effects of nitrous oxide supplementation. PMID:27525256

  14. Classification of EEG bursts in deep sevoflurane, desflurane and isoflurane anesthesia using AR-modeling and entropy measures.

    PubMed

    Lipping, Tarmo; Stålnacke, Juha; Olejarczyk, Elzbieta; Marciniak, Radoslaw; Jäntti, Ville

    2013-01-01

    A study relating signal patterns of burst onsets in burst suppression EEG to the anesthetic agent or anesthesia induction protocol is presented. A dataset of 82 recordings of sevoflurane, isoflurane and desflurane anesthesia underlies the study. 3 second segments from the onset of altogether 3214 bursts are described using AR model parameters, spectral entropy and sample entropy as features. The features are clustered using the K-means algorithm. The results indicate that no clear cut distinction can be made between the burst patterns induced by the mentioned anesthetics although bursts of certain properties are more common in certain patient groups. Several directions for further investigations are proposed based on visual inspection of the recordings. PMID:24110878

  15. Impairment of phagocytic functions of alveolar macrophages by hydrogen peroxide

    SciTech Connect

    Oosting, R.S.; van Bree, L.; van Iwaarden, J.F.; van Golde, L.M.; Verhoef, J. )

    1990-08-01

    Hydrogen peroxide (H2O2) inhibited phagocytosis and superoxide anion production by rat alveolar macrophages. The inhibition was irreversible and concentration and exposure time dependent. The potential relationship between H2O2-induced biochemical perturbations and impaired alveolar macrophage phagocytic functions was investigated. Alveolar macrophage viability and Fc receptor binding capacity were not affected by H2O2. There was probably no correlation between a H2O2-induced rise in cytosolic (Ca2+) ((Ca2+)i) and the impairment of phagocytosis by alveolar macrophages, as was suggested by the following findings. First, the H2O2-induced rise in (Ca2+)i could be inhibited by chelation of extracellular Ca2+, whereas the H2O2-induced impairment of phagocytosis could not. Second, the H2O2-induced rise in (Ca2+)i was reversible, whereas the impairment of phagocytosis was not. And finally, a rise in (Ca2+)i by incubation of alveolar macrophages with the calcium ionophore A23187 did not affect phagocytosis. Various experiments suggested that ATP depletion may play an important role in the H2O2 toxicity for alveolar macrophages. Comparable concentrations of H2O2 caused an irreversible decrease both in cellular ATP and in phagocytosis and superoxide production by alveolar macrophages. In addition, time course of ATP depletion and induction of impaired alveolar macrophage function were similar. In view of the fact that the strong oxidant H2O2 may react with a large variety of biological substances, possible other toxic lesions may not be excluded as underlying mechanism for H2O2-induced inhibition of phagocytic functions of alveolar macrophages.

  16. Isoflurane Preconditioning Elicits Competent Endogenous Mechanisms of Protection from Oxidative Stress in Cardiomyocytes Derived from Human Embryonic Stem Cells

    PubMed Central

    Sepac, Ana; Sedlic, Filip; Si-Tayeb, Karim; Lough, John; Duncan, Stephen A.; Bienengraeber, Martin; Park, Frank; Kim, Jinhee; Bosnjak, Zeljko J.

    2010-01-01

    Background Human embryonic stem cell (hESC)-derived cardiomyocytes potentially represent a powerful experimental model complementary to myocardium obtained from patients, relatively inaccessible for research purposes. We tested whether anesthetic-induced preconditioning (APC) with isoflurane elicits competent protective mechanisms in hESC-derived cardiomyocytes against oxidative stress to be used as a model of human cardiomyocytes for studying preconditioning. Methods H1 hESC cell line was differentiated into cardiomyocytes using growth factors activin A and bone morphogenetic protein-4. Living ventricular hESC-derived cardiomyocytes were identified using lentiviral vector expressing a reporter gene (enhanced green fluorescent protein) driven by a cardiac-specific human myosin light chain 2v promoter. Mitochondrial membrane potential, reactive oxygen species production, opening of mitochondrial permeability transition pore, and survival of hESC-derived cardiomyocytes were assessed using confocal microscopy. Oxygen consumption was measured in contracting cell clusters. Results Differentiation yielded a high percentage (∼85%) of cardiomyocytes in beating clusters that were positive for cardiac-specific markers and exhibited action potentials resembling mature cardiomyocytes. Isoflurane depolarized mitochondria, attenuated oxygen consumption, and stimulated generation of reactive oxygen species. APC protected these cells from oxidative stress-induced death and delayed mitochondrial permeability transition pore opening. Conclusions APC elicits competent protective mechanisms against oxidative stress in hESC-derived cardiomyocytes, suggesting the feasibility to use these cells as a model of human cardiomyocytes for studying APC and potentially other treatments/diseases. Our differentiation protocol is very efficient and yields a high percentage of cardiomyocytes. These results also suggest a promising ability of APC to protect and improve engraftment of h

  17. Alveolar-cell carcinoma: a problem in sputum cytodiagnosis.

    PubMed Central

    Spriggs, A I; Cole, M; Dunnill, M S

    1982-01-01

    Cytology and histology are correlated in a series of 22 cases chosen to illustrate the differential diagnosis between clusters of benign bronchial or bronchiolar cells seen in sputum, and those of alveolar cell carcinoma or adenocarcinoma with alveolar spread. Alveolar-cell carcinoma is characterised by clusters of small epithelial cells in spherical or irregular formations, none showing enough polarity to distinguish a smooth or palisaded surface. The appearances are most distinctive if vacuolation is absent. The diagnosis cannot, however, be confidently made in all cases from morphological features of cells in sputum. Images PMID:6294147

  18. Crazy paving radiography finding in asymptomatic pulmonary alveolar proteinosis.

    PubMed

    Choi, Young Rak; Chang, You-Jin; Kim, Si Wook; Choe, Kang Hyeon; Lee, Ki Man; An, Jin-Young

    2015-06-01

    Pulmonary alveolar proteinosis is a rare disorder characterized by alveolar accumulation of surfactant phospholipids and protein components. The symptoms and prognosis are extremely variable. Bronchoalveolar lavage fluid and/or transbronchial lung biopsy are useful for diagnosis; surgical lung biopsy is often unnecessary but useful in the focal involvement. We report a case of pulmonary alveolar proteinosis in a 50-year-old woman, confirmed by a video-assisted thoracoscopic surgery biopsy from the initial focal involvement, with normal bronchoalveolar lavage and transbronchial lung biopsy findings. PMID:25182335

  19. Desquamative alveolar disease (desquamative interstitial pneumonia): case report 1

    PubMed Central

    Cruz, Edgardo; Rodriguez, Jaime; Lisboa, Carmen; Ferretti, Ricardo

    1969-01-01

    Desquamative interstitial pneumonia is a disease characterized by massive alveolar cell proliferation and desquamation with sparse interstitial involvement. The reported case shows an unusually widespread radiographic reticulo-nodular image and abundant alveolar cells in the sputum. Functional studies reveal the expected diffusion defect with practically normal mechanical properties of the lung, in contrast with interstitial fibrosing lung diseases. On the basis of the pathological findings, especially the behaviour of alveolar cells, the individuality of this disease is discussed. We think that it is different from other diseases classed as varieties of a single disease or as different entities under the names of primary interstitial fibrosis or chronic fibrosing alveolitis. Images PMID:5822250

  20. Manipulations of extracellular Loop 2 in α1 GlyR ultra-sensitive ethanol receptors (USERs) enhance receptor sensitivity to isoflurane, ethanol, and lidocaine, but not propofol

    PubMed Central

    Naito, Anna; Muchhala, Karan H.; Trang, Janice; Asatryan, Liana; Trudell, James R.; Homanics, Gregg E.; Alkana, Ronald L.; Davies, Daryl L.

    2015-01-01

    We recently developed Ultra-Sensitive Ethanol Receptors (USERs) as a novel tool for investigation of single receptor subunit populations sensitized to extremely low ethanol concentrations that do not affect other receptors in the nervous system. To this end, we found that mutations within the extracellular Loop 2 region of glycine receptors (GlyRs) and γ-aminobutyric acid type A receptors (GABAARs) can significantly increase receptor sensitivity to micro-molar concentrations of ethanol resulting in up to a 100-fold increase in ethanol sensitivity relative to wild type (WT) receptors. The current study investigated: 1) Whether structural manipulations of Loop 2 in α1 GlyRs could similarly increase receptor sensitivity to other anesthetics; and 2) If mutations exclusive to the C-terminal end of Loop 2 are sufficient to impart these changes. We expressed α1 GlyR USERs in Xenopus oocytes and tested the effects of three classes of anesthetics, isoflurane (volatile), propofol (intravenous), and lidocaine (local), known to enhance glycine-induced chloride currents using two-electrode voltage clamp electrophysiology. Loop 2 mutations produced a significant 10-fold increase in isoflurane and lidocaine sensitivity, but no increase in propofol sensitivity compared to WT α1 GlyRs. Interestingly, we also found that structural manipulations in the C-terminal end of Loop 2 were sufficient and selective for α1 GlyR modulation by ethanol, isoflurane, and lidocaine. These studies are the first to report the extracellular region of α1 GlyRs as a site of lidocaine action. Overall, the findings suggest that Loop 2 of α1 GlyRs is a key region that mediates isoflurane and lidocaine modulation. Moreover, the results identify important amino acids in Loop 2 that regulate isoflurane, lidocaine, and ethanol action. Collectively, these data indicate the commonality of the sites for isoflurane, lidocaine, and ethanol action, and the structural requirements for allosteric modulation on

  1. Minimum Competency in Secondary Education.

    ERIC Educational Resources Information Center

    De Landsheere, Viviane

    1987-01-01

    Discusses issues related to the movement toward minimum competency in secondary education. Addresses the problem of defining minimum competency and the dangers of imposed standardization. Identifies three conceptualizations of minimum competency as: (1) the narrowly educational standpoint, (2) the concern with functional literacy, and (3) a more…

  2. Design for Minimum Risk

    NASA Technical Reports Server (NTRS)

    Wetherholt, Jon; Heimann, Timothy J.

    2010-01-01

    Design for Minimum Risk (DFMR) is a term used by NASA programs as an expansion of the general hazard reduction process where if an identified hazard cannot be eliminated, the design is modified to reduce the associated mishap risk to an acceptable level. DFMR is a set of specific requirements to minimize risk. DFMR is not well understood and there are many misconceptions concerning the meaning and use. This paper will provide insight into the use of DFMR for space applications; it s comparison to other hazard mitigation strategies and examples of how the approach has been used in the past. It will also highlight documents used by NASA on various programs to determine DFMR.

  3. Pulmonary Alveolar Proteinosis: A Rare Cause of Respiratory Failure.

    PubMed

    Munir, Zeeshan; Khosa, Muhammad Zeeshan; Qazi, Muhammad Yaqoob

    2015-07-01

    Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome in the paediatric age group and characterized by intra-alveolar accumulation of proteinaceous phospholipid-laden material called surfactant. The diagnosis is made by High Resolution Computed Tomography (HRCT) chest which shows characteristic crazy paving appearance and diagnosis confirmed by Bronchoalveolar Lavage (BAL). We report two cases. First was a 9-month old infant who presented with respiratory distress and peripheral cyanosis since birth. He was diagnosed on High Resolution Computed Tomography (HRCT) chest as a case of pulmonary alveolar proteinosis and broncho-alveolar lavage confirmed his diagnosis. Second case was a 10-year old female child who had a history of repeated chest infections for 5 years and now presented with cough and respiratory distress for 45 days. She was also diagnosed on HRCT chest but unfortunately she died before bronchoalveolar lavage. PMID:26208564

  4. Cytotoxic effect of uranium dioxide on rat alveolar macrophages

    SciTech Connect

    Tasat, D.R.; de Rey, B.M.

    1987-10-01

    Alveolar macrophages obtained by bronchial lavage were used to assess the response of these cells to cultivation in media containing increasing concentrations of particulate UO/sub 2/. The characteristic time course of uranium effects on alveolar macrophages was determined by analyzing cell viability and incorporation of uranium particles. This study reveals the ability of alveolar macrophages to phagocytize uranium particles despite the high toxicity the metal exerts on cell membranes. However, lethal effects soon become evident. Ultrastructural analysis showed uranium particles confined within membrane bound vacuoles or free in the cytoplasm. Marked ultrastructural alterations consistent with cell death were frequently observed. The elimination of the first biological barrier hinders the scavenging of particulate contaminants in alveolar spaces, thus favoring the translocation to target organs.

  5. Primary Cerebral Alveolar Echinococcosis: Mycology to the Rescue

    PubMed Central

    Goehringer, François; Umhang, Gérald; Gauchotte, Guillaume; Hénard, Sandrine; Boué, Franck; May, Thierry; Machouart, Marie

    2014-01-01

    A case of primary cerebral alveolar echinococcosis with a favorable outcome is reported. A universal fungal PCR enabled this diagnosis, while the initial serological analysis remained noncontributive. PMID:24478516

  6. AMBIENT PARTICULATE MATTER DECREASED IN HUMAN ALVEOLAR MACHROPHAGE CYTOKINE RELEASE

    EPA Science Inventory

    Human exposure to ambient airborne particulate matter (PM) is associated with cardiopulmonary mortality and morbidity, including increased hospitalizations for lung infection. Normal lung immune responses to bacterial infection include alveolar macrophage cytokine production and...

  7. Lung epithelial cells modulate the inflammatory response of alveolar macrophages.

    PubMed

    Rubovitch, Vardit; Gershnabel, Shoham; Kalina, Moshe

    2007-12-01

    The goal of this study was to examine the effect of alveolar epithelial cells on inflammatory responses in macrophages. Lung epithelial cells (either rat RLE-6TN or human A549 cells) reduced LPS-induced NO production in alveolar macrophages (AM) in a contact-independent mechanism. The inhibitory effect of the epithelial cells was present already at the transcriptional level: LPS-induced inducible NO synthase (iNOS) expression was significantly smaller. Surfactant protein A (SP-A)-induced NO production by alveolar macrophages was also reduced in the presence of A549 cells, though, by a different kinetics. LPS-induced interleukin-6 (IL-6) production (another inflammatory pathway) by alveolar macrophages was also reduced in the presence of RLE-6TN cells. These data suggest a role for lung epithelial cells in the complicated modulation of inflammatory processes, and provide an insight into the mechanism underlying. PMID:17851743

  8. *Ambient Particluate Matter Supresses Alveolar Macrophage Cytokine Response to Lipopolysaccharide

    EPA Science Inventory

    Reports link ambient particulate matter (PM) exposure with cardiopulmonary mortality and morbidity, including the exacerbation of inflammatory disease and increased hospitalization for lung infections. Alveolar macrophages (AM) play an important defense role against infections v...

  9. Immediate responses of arterial blood pressure and heart rate to sudden inhalation of high concentrations of isoflurane in normotensive and hypertensive patients.

    PubMed

    Ishikawa, T; Nishino, T; Hiraga, K

    1993-11-01

    Inhalation of pungent volatile anesthetics elicits respiratory reflex responses. To clarify whether an upper airway irritation produced by pungent anesthetics can also induce circulatory reflex responses that are clinically significant, a sudden administration of 5% isoflurane by mask was performed during continuous measurement of arterial blood pressure (BP) and heart rate (HR) in eight normotensive and eight hypertensive patients anesthetized with thiamylal and paralyzed with vecuronium. The sudden administration of 5% isoflurane caused immediate increases in BP, HR, and rate pressure products (RPP) in both normotensive and hypertensive patients. The responses observed were more pronounced in hypertensive than in normotensive patients. The circulatory changes in hypertensive patients were sufficient to be clinically significant. Our findings suggest that sudden administration of a high concentration of pungent volatile anesthetics may be associated with transient hypertensive responses in hypertensive patients with coronary artery disease. PMID:8214702

  10. Alveolar bone healing process in spontaneously hypertensive rats (SHR). A radiographic densitometry study

    PubMed Central

    MANRIQUE, Natalia; PEREIRA, Cassiano Costa Silva; GARCIA, Lourdes Maria Gonzáles; MICARONI, Samuel; de CARVALHO, Antonio Augusto Ferreira; PERRI, Sílvia Helena Venturoli; OKAMOTO, Roberta; SUMIDA, Doris Hissako; ANTONIALI, Cristina

    2012-01-01

    Hypertension is one of the most important public health problems worldwide. If undiagnosed or untreated, this pathology represents a systemic risk factor and offers unfavorable conditions for dental treatments, especially those requiring bone healing. Objectives The purpose of this study was to demonstrate, by analysis of bone mineral density (BMD), that the alveolar bone healing process is altered in spontaneously hypertensive rats (SHRs). Material and Methods Wistar rats and SHRs were submitted to extraction of the upper right incisor and were euthanized 7, 14, 21, 28 and 42 days after surgery. Right maxillae were collected, radiographed and analyzed using Digora software. BMD was expressed as minimum (min), middle (med) and maximum (max) in the medium (MT) and apical (AT) thirds of the dental alveolus. Results The results were compared across days and groups. Wistar showed difference in med and max BMD in the MT between 7 and 28 and also between 14 and 28 days. The AT exhibited significant difference in med and min BMD between 7 and 28 days, as well as difference in min BMD between 28 and 42 days. SHRs showed lower med BMD in the MT at 28 days when compared to 21 and 42 days. Differences were observed across groups in med and min BMD at day 28 in the MT and AT; and in max BMD at 14, 21 and 42 days in the MT. Conclusions These results suggest that the alveolar bone healing process is delayed in SHRs comparing with Wistar rats. PMID:22666841

  11. Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2

    PubMed Central

    Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

    2016-01-01

    Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring’s learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition. PMID:27536989

  12. Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.

    PubMed

    Luo, Foquan; Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

    2016-01-01

    Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring's learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition. PMID:27536989

  13. The ability of bispectral index to detect intra-operative wakefulness during isoflurane/air anaesthesia, compared with the isolated forearm technique.

    PubMed

    Russell, I F

    2013-10-01

    Clinical signs are unreliable for guiding anaesthetic administration and it is suggested that using the bispectral index can improve anaesthetic delivery. In the current study, isoflurane administration was guided to a bispectral index range of 55-60. Intra-operative responsiveness, as assessed by the isolated forearm technique, was compared with whether the bispectral index predicted/identified a patient's appropriate hand movements in response to commands. Thirty-four women underwent major gynaecological surgery with isoflurane/air and atracurium. Eleven women responded on 32 occasions with appropriate hand movements to commands given during surgery, of which the bispectral index detected 17 (sensitivity 53%). The bispectral index suggested consciousness 660 times in the absence of any movement responses (specificity 69%). The positive predictive value of the bispectral index was 3%. The median (IQR [range]) bispectral index value associated with an intra-operative response was significantly lower than that associated with eye opening after surgery: 60 (50-68 [36-83]) vs 77 (75-84 [59-90]), respectively (p = 2.25 × 10(-8)). Conversely, end-tidal isoflurane concentration was significantly higher at intra-operative response than at eye opening: 0.3 (0.3-0.4 [0.2-0.9]) vs 0.2 (0.1-0.2 [0.1-0.3]), respectively (p = 7.36 × 10(-8)). For patients who responded more than once during surgery, the bispectral index value associated with a response was not constant. No patient had recall for surgery or the taped commands, and only one could remember dreaming (a good dream). Titrating isoflurane to target a bispectral index range of 55-60 may result in an unacceptable number of patients who are conscious during surgery (albeit without recall). PMID:24047289

  14. Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome

    NASA Astrophysics Data System (ADS)

    Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F.; An, Gary

    2013-06-01

    Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

  15. Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome.

    PubMed

    Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F; An, Gary

    2013-06-01

    Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

  16. miRNA Expression Profile and Involvement of Let-7d-APP in Aged Rats with Isoflurane-Induced Learning and Memory Impairment

    PubMed Central

    Shi, Rong; Xu, Chengshi; Wang, Yun; Cai, Jun; Yue, Yun; Wu, Anshi

    2015-01-01

    MicroRNAs (miRNAs) play a key role in different nervous system diseases. We sought to determine the role of miRNAs in isoflurane-induced learning and memory impairment in aged rats. Male Sprague-Dawley (SD) rats of 18 month were randomly assigned to control group (exposed to mock anesthesia), 2-hour group and 6-hour group (exposed to 2% isoflurane for 2 and 6 hours respectively). By Morris Water Maze, 6-hour group showed impaired learning and memory ability while 2-hour group not. As shown by miRNA array, control group and 2-hour group showed a similar miRNA expression profile. And 38 miRNAs are differently expressed in 6-hour group compared to the other 2 groups, including 21 up-regulated miRNAs and 17 down-regulated miRNAs. And 4 of the differentially expressed miRNAs were validated independently by qRT-PCR. Let-7d was downregulated in 6-hour group. Additionally, we demonstrated that amyloid precursor protein (APP) was a direct target of let-7d by Fluorescent report assay. Increased expression of APP and amyloid-β (Aβ) were found in the hippocampi of 6-hour group. Downregulation of let-7d might contribute to isoflurane-induced learning and memory impairment through upregulating its target APP, and increasing the production of Aβ subsequently. PMID:25799420

  17. Inferior Alveolar Nerve Lateralization and Transposition for Dental Implant Placement. Part I: a Systematic Review of Surgical Techniques

    PubMed Central

    Juodzbalys, Gintaras

    2015-01-01

    ABSTRACT Objectives The purpose of this first part of a two-part series was to review the literature concerning the indications, contraindications, advantages, disadvantages and surgical techniques of the lateralization and transposition of the inferior alveolar nerve, followed by the placement of an implant in an edentulous atrophic posterior mandible. Material and Methods A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed and PMC database, academic sites and books. The articles were searched from January 1997 to July 2014 and comprised English-language articles that included adult patients between 18 and 80 years old with minimal residual bone above the mandibular canal who had undergone inferior alveolar nerve (IAN) repositioning with a minimum 6 months of follow-up. Results A total of 16 studies were included in this review. Nine were related to IAN transposition, 4 to IAN lateralization and 3 to both transposition and lateralization. Implant treatment results and complications were presented. Conclusions Inferior alveolar nerve lateralization and transposition in combination with the installation of dental implants is sometimes the only possible procedure to help patients to obtain a fixed prosthesis, in edentulous atrophic posterior mandibles. With careful pre-operative surgical and prosthetic planning, imaging, and extremely precise surgical technique, this procedure can be successfully used for implant placement in edentulous posterior mandibular segments. PMID:25937873

  18. Therapy options in pulmonary alveolar proteinosis.

    PubMed

    Luisetti, Maurizio; Kadija, Zamir; Mariani, Francesca; Rodi, Giuseppe; Campo, Ilaria; Trapnell, Bruce C

    2010-08-01

    Pulmonary alveolar proteinosis is a rare condition characterized by the accumulation of lipoproteinaceous material within the airspaces, resulting in impaired gas transfer, and clinical manifestations ranging from asymptomatic to severe respiratory failure. To the best of the authors' knowledge, there are only a few conditions whose natural history has been so dramatically changed by the influence of advances in basic science, clinical medicine, and translational research in therapeutic approaches. Whole-lung lavage is the current standard of care and it plays a critical role as a modifier factor of the natural history of proteinosis. That notwithstanding, the identification of autoantibodies neutralizing granulocyte-macrophage colony-stimulating factor in serum and lung of patients affected by the form of proteinosis previously referred to as idiopathic, has opened the way to novel therapeutic options, such as supplementation of exogenous granulocyte-macrophage colony-stimulating factor, or strategies aimed at reducing the levels of the autoantibodies. The aim of this paper is to provide an updated review of the current therapeutic approach to proteinosis. PMID:20647242

  19. Cardiovascular risk in pulmonary alveolar proteinosis.

    PubMed

    Manali, Effrosyni D; Papadaki, Georgia; Konstantonis, Dimitrios; Tsangaris, Iraklis; Papaioannou, Andriana I; Kolilekas, Likurgos; Schams, Andrea; Kagouridis, Konstantinos; Karakatsani, Anna; Orfanos, Stylianos; Griese, Matthias; Papiris, Spyros A

    2016-02-01

    We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O2, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R(2) = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs' physiologic derangement will be addressed in future studies. PMID:26558331

  20. Alveolar rhabdomyosarcoma after treatment of osteosarcoma.

    PubMed

    Kasahara, Yasushi; Iwabuchi, Haruko; Takachi, Takayuki; Hosokai, Ryosuke; Yoshida, Sakiko; Imamura, Masaru; Watanabe, Akihiro; Umezu, Hajime; Hotta, Tetsuo; Ogose, Akira; Imai, Chihaya

    2013-08-01

    Secondary rhabdomyosarcoma (RMS) after treatment of osteosarcoma (OS) is rare. Reported here is the case of a metachronous RMS in the nasal cavity, developing 12 years after successful treatment of non-metastatic OS. The patient was diagnosed as having OS of the femur at 2 years of age. Chemotherapy for OS included doxorubicin (cumulative dose, 488 mg/m(2) ). No radiotherapy was given. There was no family history suggestive of cancer predisposition syndrome. At 14 years of age, alveolar RMS was diagnosed on histopathology. PAX3-FKHR fusion transcripts were detected on reverse transcription-polymerase chain reaction. Germline TP53 mutation was not seen on standard DNA sequencing. The occurrence of secondary sarcomas, in the Children's Cancer Survivor study conducted in North America, has been associated with high cumulative doses of anthracyclines, which may also have played a role in the development of RMS in the present case. In the future, novel molecular technologies might uncover genetic cancer predisposition in patients with metachronous cancers. PMID:23910806

  1. Populations at Risk for Alveolar Echinococcosis, France

    PubMed Central

    Piarroux, Martine; Piarroux, Renaud; Knapp, Jenny; Bardonnet, Karine; Dumortier, Jérôme; Watelet, Jérôme; Gerard, Alain; Beytout, Jean; Abergel, Armand; Bresson-Hadni, Solange

    2013-01-01

    During 1982–2007, alveolar echinococcosis (AE) was diagnosed in 407 patients in France, a country previously known to register half of all European patients. To better define high-risk groups in France, we conducted a national registry-based study to identify areas where persons were at risk and spatial clusters of cases. We interviewed 180 AE patients about their way of life and compared responses to those of 517 controls. We found that almost all AE patients lived in 22 départements in eastern and central France (relative risk 78.63, 95% CI 52.84–117.02). Classification and regression tree analysis showed that the main risk factor was living in AE-endemic areas. There, most at-risk populations lived in rural settings (odds ratio [OR] 66.67, 95% CI 6.21–464.51 for farmers and OR 6.98, 95% CI 2.88–18.25 for other persons) or gardened in nonrural settings (OR 4.30, 95% CI 1.82–10.91). These findings can help sensitization campaigns focus on specific groups. PMID:23647623

  2. Lung vasculitis and alveolar hemorrhage: pathology.

    PubMed

    Fishbein, Gregory A; Fishbein, Michael C

    2011-06-01

    Pulmonary vasculitides are a diverse group of limited and systemic disorders associated with inflammation of pulmonary vessels and parenchyma. These diseases often have distinctive clinical, serological, and histopathological features-extrapulmonary sites of involvement, circulating autoantibodies, predispositions for small or large vessels, and others. Some have characteristic inflammatory lesions; others are characterized by the absence of such lesions. Frequently pathological findings overlap, rendering classification, and diagnosis a challenge. The anti-neutrophil cytoplasmic antibody (ANCA)-associated small-vessel diseases constitute the major pulmonary vasculitides. These include Wegener granulomatosis (WG), Churg Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Less frequently, diseases such as polyarteritis nodosa, Takayasu arteritis, Behçet syndrome, and connective tissue diseases may involve pulmonary vessels, but these entities are better associated with extrapulmonary disease. Diffuse alveolar hemorrhage (DAH) is a severe manifestation of pulmonary vasculitis. DAH is most commonly seen in small-vessel vasculitides, specifically MPA and WG. Other syndromes associated with DAH include Goodpasture syndrome, Henoch-Schönlein purpura, and systemic lupus erythematosus. Less commonly, DAH may be secondary to infection or drugs/toxins. Furthermore, in the absence of discernable systemic disease, DAH may be idiopathic-referred to as isolated pulmonary capillaritis (IPC) or idiopathic pulmonary hemosiderosis (IPH), depending on the presence of capillaritis. PMID:21674412

  3. [Alveolar soft part sarcoma in pediatric patients].

    PubMed

    Paillard, Catherine; Coulomb, Aurore; Helfre, Sylvie; Orbach, Daniel

    2015-09-01

    Alveolar soft part sarcoma, ASPS, is a rare malignant tumor, with preferential primary localization in limbs, usually occurring in adolescents and young adults. This sarcoma, well defined histologically and at molecular level, has an indolent course, but a high potential metastatic pulmonary and cerebral evolution, sometimes late. ASPS is characterized by an almost specific translocation t(X, 17)(p11;25) which creates a fusion protein, APSL-TFE3, acting as an aberrant transcription factor. An in-bloc resection of the primary tumor is the treatment of choice in cases of localized disease. Conventional chemotherapy is generally ineffective. The role of radiotherapy is discussed in case of micro- or macroscopical incomplete residue. It seems to reduce local recurrence, but did not influence overall survival. The 5 years survival rate in children, adolescents and young adults is close to 80% in case of localized disease but poorer in presence of metastases. Recently, systemic anti-tumoral treatments have been focused on the use of targeted therapies. Anti-angiogenic drugs and tyrosine kinase inhibitors are the most promising approaches, but require further study. Prognostic risk factors in the literature are age (>10Y), tumor size (>5cm) and presence of metastases. This article reviews the clinical manifestations, diagnosis modalities, radiographic characteristics and therapeutic strategy of this disease in the pediatric population. PMID:26235420

  4. Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages.

    PubMed

    Chen, S; Kammerl, I E; Vosyka, O; Baumann, T; Yu, Y; Wu, Y; Irmler, M; Overkleeft, H S; Beckers, J; Eickelberg, O; Meiners, S; Stoeger, T

    2016-06-01

    The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes involved in shaping adaptive immune responses, but their role in innate immune signaling is still elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages, highly specialized tissue macrophages of the alveolar lung surface. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits, low molecular mass protein 2 (LMP2), LMP7 and multicatalytic endopeptidase complex-like 1, which was accompanied by increased immunoproteasome activity in M1 cells. Deficiency of LMP7 had no effect on the LPS/IFNγ-triggered M1 profile indicating that immunoproteasome function is dispensable for classical alveolar macrophage activation. In contrast, IL-4 triggered alternative (M2) activation of primary alveolar macrophages was accompanied by a transcriptionally independent amplified expression of LMP2 and LMP7 and an increase in immunoproteasome activity. Alveolar macrophages from LMP7 knockout mice disclosed a distorted M2 profile upon IL-4 stimulation as characterized by increased M2 marker gene expression and CCL17 cytokine release. Comparative transcriptome analysis revealed enrichment of IL-4-responsive genes and of genes involved in cellular response to defense, wounding and inflammation in LMP7-deficient alveolar macrophages indicating a distinct M2 inflammation resolving phenotype. Moreover, augmented M2 polarization was accompanied by amplified AKT/STAT6 activation and increased RNA and protein expression of the M2 master transcription factor interferon regulatory factor 4 in LMP7(-/-) alveolar macrophages. IL-13 stimulation of LMP7-deficient macrophages induced a similar M2-skewed profile indicative for augmented signaling via the IL-4 receptor α (IL4Rα). IL4Rα expression was generally

  5. Modeling Alveolar Epithelial Cell Behavior In Spatially Designed Hydrogel Microenvironments

    NASA Astrophysics Data System (ADS)

    Lewis, Katherine Jean Reeder

    The alveolar epithelium consists of two cell phenotypes, elongated alveolar type I cells (AT1) and rounded alveolar type II cells (ATII), and exists in a complex three-dimensional environment as a polarized cell layer attached to a thin basement membrane and enclosing a roughly spherical lumen. Closely surrounding the alveolar cysts are capillary endothelial cells as well as interstitial pulmonary fibroblasts. Many factors are thought to influence alveolar epithelial cell differentiation during lung development and wound repair, including physical and biochemical signals from the extracellular matrix (ECM), and paracrine signals from the surrounding mesenchyme. In particular, disrupted signaling between the alveolar epithelium and local fibroblasts has been implicated in the progression of several pulmonary diseases. However, given the complexity of alveolar tissue architecture and the multitude of signaling pathways involved, designing appropriate experimental platforms for this biological system has been difficult. In order to isolate key factors regulating cellular behavior, the researcher ideally should have control over biophysical properties of the ECM, as well as the ability to organize multiple cell types within the scaffold. This thesis aimed to develop a 3D synthetic hydrogel platform to control alveolar epithelial cyst formation, which could then be used to explore how extracellular cues influence cell behavior in a tissue-relevant cellular arrangement. To accomplish this, a poly(ethylene glycol) (PEG) hydrogel network containing enzymatically-degradable crosslinks and bioadhesive pendant peptides was employed as a base material for encapsulating primary alveolar epithelial cells. First, an array of microwells of various cross-sectional shapes was photopatterned into a PEG gel containing photo-labile crosslinks, and primary ATII cells were seeded into the wells to examine the role of geometric confinement on differentiation and multicellular arrangement

  6. Equivalence to the Minimum Qualifications

    ERIC Educational Resources Information Center

    Academic Senate for California Community Colleges, 2006

    2006-01-01

    In 1988 the Community College Reform Act (AB 1725) began a phase out of credentials in favor of a process for establishing minimum qualifications and the determination of equivalencies that are at least equal to the state-adopted minimum qualifications for a particular discipline. According to Education Code sections 87359 and 87360, someone…

  7. The Global Burden of Alveolar Echinococcosis

    PubMed Central

    Torgerson, Paul R.; Keller, Krista; Magnotta, Mellissa; Ragland, Natalie

    2010-01-01

    Background Human alveolar echinococcosis (AE) is known to be common in certain rural communities in China whilst it is generally rare and sporadic elsewhere. The objective of this study was to provide a first estimate of the global incidence of this disease by country. The second objective was to estimate the global disease burden using age and gender stratified incidences and estimated life expectancy with the disease from previous results of survival analysis. Disability weights were suggested from previous burden studies on echinococcosis. Methodology/Principal Findings We undertook a detailed review of published literature and data from other sources. We were unable to make a standardised systematic review as the quality of the data was highly variable from different countries and hence if we had used uniform inclusion criteria many endemic areas lacking data would not have been included. Therefore we used evidence based stochastic techniques to model uncertainty and other modelling and estimating techniques, particularly in regions where data quality was poor. We were able to make an estimate of the annual global incidence of disease and annual disease burden using standard techniques for calculation of DALYs. Our studies suggest that there are approximately 18,235 (CIs 11,900–28,200) new cases of AE per annum globally with 16,629 (91%) occurring in China and 1,606 outside China. Most of these cases are in regions where there is little treatment available and therefore will be fatal cases. Based on using disability weights for hepatic carcinoma and estimated age and gender specific incidence we were able to calculate that AE results in a median of 666,434 DALYs per annum (CIs 331,000-1.3 million). Conclusions/Significance The global burden of AE is comparable to several diseases in the neglected tropical disease cluster and is likely to be one of the most important diseases in certain communities in rural China on the Tibetan plateau. PMID:20582310

  8. Retinoic acid in alveolar development, maintenance and regeneration.

    PubMed Central

    Maden, Malcolm; Hind, Matthew

    2004-01-01

    Recent data suggest that exogenous retinoic acid (RA), the biologically active derivative of vitamin A, can induce alveolar regeneration in a rat model of experimental emphysema. Here, we describe a mouse model of disrupted alveolar development using dexamethasone administered postnatally. We show that the effects of dexamethasone are concentration dependent, dose dependent, long lasting and result in a severe loss of alveolar surface area. When RA is administered to these animals as adults, lung architecture and the surface area per unit of body weight are completely restored to normal. This remarkable effect may be because RA is required during normal alveolar development and administering RA re-awakens gene cascades used during development. We provide evidence that RA is required during alveologenesis in the mouse by showing that the levels of the retinoid binding proteins, the RA receptors and two RA synthesizing enzymes peak postnatally. Furthermore, an inhibitor of RA synthesis, disulphiram, disrupts alveologenesis. We also show that RA is required throughout life for the maintenance of lung alveoli because when rats are deprived of dietary retinol they lose alveoli and show the features of emphysema. Alveolar regeneration with RA may therefore be an important novel therapeutic approach to the treatment of respiratory diseases characterized by a reduced gas-exchanging surface area such as bronchopulmonary dysplasia and emphysema for which there are currently no treatments. PMID:15293808

  9. Alveolar targeting of aerosol pentamidine. Toward a rational delivery system

    SciTech Connect

    Simonds, A.K.; Newman, S.P.; Johnson, M.A.; Talaee, N.; Lee, C.A.; Clarke, S.W. )

    1990-04-01

    Nebulizer systems that deposit a high proportion of aerosolized pentamidine on large airways are likely to be associated with marked adverse side effects, which may lead to premature cessation of treatment. We have measured alveolar deposition and large airway-related side effects (e.g., cough, breathlessness, and effect on pulmonary function) after aerosolization of 150 mg pentamidine isethionate labeled with {sup 99m}Tc-Sn-colloid. Nine patients with AIDS were studied using three nebulizer systems producing different droplet size profiles: the Acorn System 22, Respirgard II, and Respirgard II with the inspiratory baffle removed. Alveolar deposition was greatest and side effects least with the nebulizer producing the smallest droplet size profile (Respirgard II), whereas large airway-related side effects were prominent and alveolar deposition lowest with the nebulizer producing the largest droplet size (Acorn System 22). Values for alveolar deposition and adverse airway effects were intermediate using the Respirgard with inspiratory baffle removed, thus indicating the importance of the baffle valve in determining droplet size. Addition of a similar baffle valve to the Acorn System 22 produced a marked improvement in droplet size profile. Selection of a nebulizer that produces an optimal droplet size range offers the advantage of enhancing alveolar targeting of aerosolized pentamidine while reducing large airway-related side effects.

  10. Is alveolar cleft reconstruction still controversial? (Review of literature)

    PubMed Central

    Seifeldin, Sameh A.

    2015-01-01

    Cleft lip and palate (CL/P) is a frequent congenital malformation that manifests in several varieties including unilateral or bilateral and complete or incomplete. Alveolar cleft reconstruction remains controversial with regard to timing, graft materials, surgical techniques, and methods of evaluation. Many studies have been conducted addressing these points to develop an acceptable universal protocol for managing CL/P. The primary goal of alveolar cleft reconstruction in CL/P patients is to provide a bony bridge at the cleft site that allows maxillary arch continuity, oronasal fistula repair, eruption of the permanent dentition into the newly formed bone, enhances nasal symmetry through providing alar base support, orthodontic movement and placement of osseointegrated implants when indicated. Other goals include improving speech, improvement of periodontal conditions, establishing better oral hygiene, and limiting growth disturbances. In order to rehabilitate oral function in CL/P patients alveolar bone grafting is necessary. Secondary bone grafting is the most widely accepted method for treating alveolar clefts. Autogenous bone graft is the primary source for reconstructing alveolar cleft defects and is currently the preferred grafting material. PMID:26792963

  11. The effect of exogenous surfactant on alveolar interdependence.

    PubMed

    Salito, Caterina; Aliverti, Andrea; Mazzuca, Enrico; Rivolta, Ilaria; Miserocchi, Giuseppe

    2015-05-01

    To investigate the nature of alveolar mechanical interdependence, we purposefully disturbed the equilibrium condition by administering exogenous surfactant in physiological non-surfactant deprived conditions. Changes in alveolar morphology induced by intra-tracheal delivery of CUROSURF were evaluated after opening a pleural window allowing in-vivo microscopic imaging of sub-pleural alveoli in 6 male anesthetized, tracheotomized and mechanically ventilated rabbits. Surfactant instillation increased the surface area of alveoli smaller than 20,000 μm(2) up to ∼ 50% at 15 min after instillation, reflecting a lowering of surface tension due to local surfactant enrichment. Conversely, for alveoli greater than 20,000 μm(2), surface area decreased by ∼ 5%. Opposite changes in alveolar surface are interpreted as reflecting a new inter-alveolar mechanical equilibrium modified by local surfactant distribution and by a decrease in lung distending pressure. We propose that smaller alveoli, representing the majority of alveolar population, might mostly contribute to improve the oxygenation index following surfactant replacement therapy in case of surfactant deficiency. PMID:25600053

  12. Osteogenic Effect of High-frequency Acceleration on Alveolar Bone

    PubMed Central

    Alikhani, M.; Khoo, E.; Alyami, B.; Raptis, M.; Salgueiro, J.M.; Oliveira, S.M.; Boskey, A.; Teixeira, C.C.

    2012-01-01

    Mechanical stimulation contributes to the health of alveolar bone, but no therapy using the osteogenic effects of these stimuli to increase alveolar bone formation has been developed. We propose that the application of high-frequency acceleration to teeth in the absence of significant loading is osteogenic. Sprague-Dawley rats were divided among control, sham, and experimental groups. The experimental group underwent localized accelerations at different frequencies for 5 min/day on the occlusal surface of the maxillary right first molar at a very low magnitude of loading (4 µε). Sham rats received a similar load in the absence of acceleration or frequency. The alveolar bone of the maxilla was evaluated by microcomputed tomography (µCT), histology, fluorescence microscopy, scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR imaging), and RT-PCR for osteogenic genes. Results demonstrate that application of high-frequency acceleration significantly increased alveolar bone formation. These effects were not restricted to the area of application, and loading could be replaced by frequency and acceleration. These studies propose a simple mechanical therapy that may play a significant role in alveolar bone formation and maintenance. PMID:22337699

  13. Social Security's special minimum benefit.

    PubMed

    Olsen, K A; Hoffmeyer, D

    Social Security's special minimum primary insurance amount (PIA) provision was enacted in 1972 to increase the adequacy of benefits for regular long-term, low-earning covered workers and their dependents or survivors. At the time, Social Security also had a regular minimum benefit provision for persons with low lifetime average earnings and their families. Concerns were rising that the low lifetime average earnings of many regular minimum beneficiaries resulted from sporadic attachment to the covered workforce rather than from low wages. The special minimum benefit was seen as a way to reward regular, low-earning workers without providing the windfalls that would have resulted from raising the regular minimum benefit to a much higher level. The regular minimum benefit was subsequently eliminated for workers reaching age 62, becoming disabled, or dying after 1981. Under current law, the special minimum benefit will phase out over time, although it is not clear from the legislative history that this was Congress's explicit intent. The phaseout results from two factors: (1) special minimum benefits are paid only if they are higher than benefits payable under the regular PIA formula, and (2) the value of the regular PIA formula, which is indexed to wages before benefit eligibility, has increased faster than that of the special minimum PIA, which is indexed to inflation. Under the Social Security Trustees' 2000 intermediate assumptions, the special minimum benefit will cease to be payable to retired workers attaining eligibility in 2013 and later. Their benefits will always be larger under the regular benefit formula. As policymakers consider Social Security solvency initiatives--particularly proposals that would reduce benefits or introduce investment risk--interest may increase in restoring some type of special minimum benefit as a targeted protection for long-term low earners. Two of the three reform proposals offered by the President's Commission to Strengthen

  14. Pulmonary contusion induces alveolar type 2 epithelial cell apoptosis: role of alveolar macrophages and neutrophils.

    PubMed

    Seitz, Daniel H; Perl, Mario; Mangold, Stefanie; Neddermann, Anne; Braumüller, Sonja T; Zhou, Shaoixa; Bachem, Max G; Huber-Lang, Markus S; Knöferl, Markus W

    2008-11-01

    Alveolar type 2 (AT-2) cell apoptosis is an important mechanism during lung inflammation, lung injury, and regeneration. Blunt chest trauma has been shown to activate inflammatory cells such as alveolar macrophages (AMs) or neutrophils (polymorphonuclear granulocytes [PMNs]), resulting in an inflammatory response. The present study was performed to determine the capacity of different components/cells of the alveolar compartment (AMs, PMNs, or bronchoalveolar lavage [BAL] fluids) to induce apoptosis in AT-2 cells following blunt chest trauma. To study this, male Sprague-Dawley rats were subjected to either sham procedure or blunt chest trauma induced by a single blast wave. Various time points after injury (6 h to 7 d), the lungs were analyzed by immunohistochemistry, for AT-2 cells, or with antibodies directed against caspase 3, caspase 8, Fas, Fas ligand (FasL), BAX, and BCL-2. Bronchoalveolar lavage concentrations of TNF-alpha, IL-1beta, and soluble FasL were determined by enzyme-linked immunosorbent assay. Furthermore, cultures of AT-2 cells isolated from healthy rats were incubated with supernatants of AMs, PMNs, or BAL fluids obtained from either trauma or sham-operated animals in the presence or absence of oxidative stress. Annexin V staining or TUNEL (terminal deoxynucleotidyl transferase) assay was used to detect apoptotic AT-2 cells. Histological evaluation revealed that the total number of AT-2 cells was significantly reduced at 48 h following trauma. Fas, FasL, active caspase 8, and active caspase 3 were markedly up-regulated in AT-2 cells after chest trauma. BAX and BCL-2 did not show any significant changes between sham and trauma. IL-1beta, but not TNF-alpha, levels were markedly increased at 24 h after the injury, and soluble FasL concentrations were significantly enhanced at 6, 12, 24, and 48 h after the insult. Apoptosis of AT-2 cells incubated with supernatants from cultured AMs, isolated at 48 h following chest trauma was markedly increased when

  15. Impaired Spatial Learning Memory after Isoflurane Anesthesia or Appendectomy in Aged Mice is Associated with Microglia Activation

    PubMed Central

    Wang, Hui-Lin; Ma, Rui-Hua; Fang, Hao; Xue, Zhang-Gang; Liao, Qing-Wu

    2015-01-01

    Postoperative cognitive dysfunction (POCD) has been one of the most common problems in elderly patients following surgery. But the specific mechanism of POCD is still not clear. To further understand the reason of these postoperative behavioral deficits, we evaluated the spatial learning memory of both adult (3 months) and aged (18 months) male mice, 3 or 28 days after isoflurane (Iso) exposure for two hours or appendectomy (App). Hippocampal microglia activation and IL-1β, TNF-α, and IFN-γ expression were also evaluated at day 3, day 14 and day 28 after Iso exposure or appendectomy. Results showed that spatial learning memory of aged, but not adult, mice was impaired after Iso exposure or appendectomy, accompanied with more hippocampal microglia activation and IL-1β, TNF-α, and IFN-γ overexpression. These findings suggest that the cognitive deficits of elderly patients who have undergone surgeries are quite possibly caused by hippocampal microglia overactivation and the subsequent inflammation. PMID:26380557

  16. Isoflurane preconditioning provides neuroprotection against stroke by regulating the expression of the TLR4 signalling pathway to alleviate microglial activation

    PubMed Central

    Sun, Meiyan; Deng, Bin; Zhao, Xiaoyong; Gao, Changjun; Yang, Lu; Zhao, Hui; Yu, Daihua; Zhang, Feng; Xu, Lixian; Chen, Lei; Sun, Xude

    2015-01-01

    Excessive microglial activation often contributes to inflammation-mediated neurotoxicity in the ischemic penumbra during the acute stage of ischemic stroke. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation via the NF-κB pathway. Isoflurane preconditioning (IP) can provide neuroprotection and inhibit microglial activation. In this study, we investigated the roles of the TLR4 signalling pathway in IP to exert neuroprotection following ischemic stroke in vivo and in vitro. The results showed that 2% IP alleviated neurological deficits, reduced the infarct volume, attenuated apoptosis and weakened microglial activation in the ischemic penumbra. Furthermore, IP down-regulated the expression of HSP 60, TLR4 and MyD88 and up-regulated inhibitor of IκB-α expression compared with I/R group in vivo. In vitro, 2% IP and a specific inhibitor of TLR4, CLI-095, down-regulated the expression of TLR4, MyD88, IL-1β, TNF-α and Bax, and up-regulated IκB-α and Bcl-2 expression compared with OGD group. Moreover, IP and CLI-095 attenuated microglial activation-induced neuronal apoptosis, and overexpression of the TLR4 gene reversed the neuroprotective effects of IP. In conclusion, IP provided neuroprotection by regulating TLR4 expression directly, alleviating microglial activation and neuroinflammation. Thus, inhibiting the activation of microglial activation via TLR4 may be a new avenue for stroke treatment. PMID:26086415

  17. Traumatic neuroma of the inferior alveolar nerve: a case report.

    PubMed

    Arribas-García, Ignacio; Alcalá-Galiano, Andrea; Gutiérrez, Ramón; Montalvo-Moreno, Juan José

    2008-03-01

    Traumatic neuromas are rare entities which characteristically arise subsequently to surgery and are usually accompanied by pain, typically neuralgic. We present an unusual case of an intraosseous traumatic neuroma of the inferior alveolar nerve following tooth extraction. A 56-year-old man consulted for paresthesias and hyperesthesia in the left mandibular region following extraction of the left mandibular third molar (#38). The panoramic radiograph revealed a radiolucent lesion in the inferior alveolar nerve canal, and CT demonstrated the existence of a mass within the canal, producing widening of the same. Nerve-sparing excisional biopsy was performed. Histopathology and immunohistochemistry were consistent with traumatic neuroma of the left inferior alveolar nerve. After 3 years of follow-up, the patient is asymptomatic and there are no signs of recurrence. PMID:18305440

  18. Rare combination of congenital heart disease and pulmonary alveolar proteinosis.

    PubMed

    Tanaka, Yuki; Miyamoto, Takashi; Yoshitake, Shuichi; Naito, Yuji; Kobayashi, Tomio

    2015-10-01

    Here, we describe a case of total anomalous pulmonary venous return with coarctation of the aorta that was diagnosed as pulmonary alveolar proteinosis at autopsy in a male infant. Surgical repair was performed at 1 day of age, but the infant died on postoperative day 51 due to respiratory insufficiency without any evidence of pulmonary venous obstruction. He had been unexpectedly diagnosed with pulmonary alveolar proteinosis and pulmonary hypoplasia on autopsy. Congenital pulmonary alveolar proteinosis is a serious condition with a high mortality rate, which should be considered in the differential diagnosis in patients with a clinical picture of pulmonary venous obstruction, because most patients are unable to survive without proper treatment. In this report, we address specific issues that should be discussed in such cases based on our recent experience. PMID:26310609

  19. European echinococcosis registry: human alveolar echinococcosis, Europe, 1982-2000.

    PubMed

    Kern, Petra; Bardonnet, Karine; Renner, Elisabeth; Auer, Herbert; Pawlowski, Zbigniew; Ammann, Rudolf W; Vuitton, Dominique A; Kern, Peter

    2003-03-01

    Surveillance for alveolar echinococcosis in central Europe was initiated in 1998. On a voluntary basis, 559 patients were reported to the registry. Most cases originated from rural communities in regions from eastern France to western Austria; single cases were reported far away from the disease-"endemic" zone throughout central Europe. Of 210 patients, 61.4% were involved in vocational or part-time farming, gardening, forestry, or hunting. Patients were diagnosed at a mean age of 52.5 years; 78% had symptoms. Alveolar echinococcosis primarily manifested as a liver disease. Of the 559 patients, 190 (34%) were already affected by spread of the parasitic larval tissue. Of 408 (73%) patients alive in 2000, 4.9% were cured. The increasing prevalence of Echinococcus multilocularis in foxes in rural and urban areas of central Europe and the occurrence of cases outside the alveolar echinococcosis-endemic regions suggest that this disease deserves increased attention. PMID:12643830

  20. Variant Inferior Alveolar Nerves and Implications for Local Anesthesia.

    PubMed

    Wolf, Kevin T; Brokaw, Everett J; Bell, Andrea; Joy, Anita

    2016-01-01

    A sound knowledge of anatomical variations that could be encountered during surgical procedures is helpful in avoiding surgical complications. The current article details anomalous morphology of inferior alveolar nerves encountered during routine dissection of the craniofacial region in the Gross Anatomy laboratory. We also report variations of the lingual nerves, associated with the inferior alveolar nerves. The variations were documented and a thorough review of literature was carried out. We focus on the variations themselves, and the clinical implications that these variations present. Thorough understanding of variant anatomy of the lingual and inferior alveolar nerves may determine the success of procedural anesthesia, the etiology of pathologic processes, and the avoidance of surgical misadventure. PMID:27269666

  1. A variant of pulmonary alveolar microlithiasis in nackt mice.

    PubMed

    Starost, M F; Benavides, F; Conti, C J

    2002-05-01

    Four adult mutant nackt mice, which demonstrate alopecia and CD4+ T-cell deficiency, and two outbred SENCAR mice (sentinels) were presented for routine health surveillance. Lesions were not observed at necropsy. Microscopically, all four nackt mice demonstrated multiple concretions that were 30-100 microm in diameter, irregularly rounded to oval, nonbirefringent, and amphophilic to basophilic. Many of the concretions appeared attached to or within the alveolar walls of all lung lobes. Approximately half of the concretions had irregular fracture lines. All concretions were periodic acid-Schiff positive, and Von Kassa staining revealed diffuse calcification. None of the concretions were associated with inflammatory cell infiltrates, and metaplastic ossification was not evident. A diagnosis of pulmonary alveolar microlithiasis, a rare disease in both humans and animals, was made based on the size and location of the concretions and the lack of an inflammatory response. This is the first report of a laboratory mouse demonstrating pulmonary alveolar microlithiasis. PMID:12014504

  2. Alveolar-filling growth pattern of sarcomatoid malignant pleural mesothelioma.

    PubMed

    Hayakawa, Takamitsu; Tajima, Shogo; Takanashi, Yusuke; Takahashi, Tsuyoshi; Neyatani, Hiroshi; Funai, Kazuhito

    2016-09-01

    A case of sarcomatoid malignant pleural mesothelioma showing extremely rare growth pattern is described. A 63-year-old man presented to our hospital with left pleural effusion. A computed tomography (CT) scan of the chest showed diffusely thickened left visceral and parietal pleura associated with intermingled pulmonary infiltrative shadowing. Biopsy of the pleura under general anaesthesia confirmed the diagnosis of sarcomatoid malignant pleural mesothelioma. The patient underwent left extra-pleural pneumonectomy. Histopathologically, the sarcomatoid spindle tumour cells changed their morphology to polygonal cells in the pulmonary parenchyma and grew upwards, filling the alveolar space without the destruction of its septa, showing an alveolar-filling growth pattern. The current report indicates a case of sarcomatoid pleural mesothelioma that shows an alveolar-filling growth pattern, despite having not been thoroughly categorized in the World Health Organization (WHO) classification. PMID:27516891

  3. Alveolar Osteitis: A Comprehensive Review of Concepts and Controversies

    PubMed Central

    Kolokythas, Antonia; Olech, Eliza; Miloro, Michael

    2010-01-01

    Alveolar osteitis, “dry socket”, remains amongst the most commonly encountered complications following extraction of teeth by general dentists and specialists. A great body of literature is devoted to alveolar osteitis addressing the etiology and pathophysiology of this condition. In addition numerous studies are available discussing methods and techniques to prevent this condition. To this date though great controversy still exists regarding the appropriate terminology used for this condition as well as the actual etiology, pathophysiology, and best methods of prevention and treatment. This article is a comprehensive critical review of the available literature addressing the concepts and controversies surrounding alveolar osteitis. We aim to assist the dental health care professional with patient preparation and management of this commonly encountered postoperative condition should be encountered. PMID:20652078

  4. [Peri-operative atelectasis and alveolar recruitment manoeuvres].

    PubMed

    Rama-Maceiras, Pablo

    2010-06-01

    Respiratory complications are a significant cause of post-operative morbidity and mortality. Peri-operative atelectasis, in particular, affects 90% of surgical patients and its effects can be prolonged, due to changes in respiratory mechanics, pulmonary circulation and hypoxaemia. Alveolar collapse is caused by certain predisposing factors, mainly by compression and absorption mechanisms. To prevent or treat these atelectasis several therapeutic strategies have been proposed, such as alveolar recruitment manoeuvres, which has become popular in the last few years. Its application in patients with alveolar collapse, but without a previous significant acute lung lesion, has some special features, therefore its use is not free of uncertainties and complications. This review describes the frequency, pathophysiology, importance and treatment of peri-operative atelectasis. Special attention is paid to treatment with recruitment manoeuvres, with the purpose of providing a basis for the their rational and appropriate use. PMID:19959274

  5. Venus ionopause during solar minimum

    NASA Technical Reports Server (NTRS)

    Mahajan, K. K.; Mayr, H. G.

    1989-01-01

    Pioneer Venus ion composition measurements are used to study the Venus ionosphere during solar minimum. It is suggested that the topside electron density profile at Venus during solar minimum has two distinct regimes. One beween 140 and 180 km is dominated by O2(+) ions which are in photochemical equilibrium. The other regime is above 180 km and is dominated by O(+) ions which are disturbed by the solar wind induced plasma transport. For Pioneer Venus, Mariner 10, and Venera 9 and 10 data, it is found that Venus exhibits a photodynamical type of ionopause during solar minimum.

  6. Mechanisms underlying the redistribution of particles among the lung's alveolar macrophages during alveolar phase clearance

    SciTech Connect

    Lehnert, B.E.; Oritz, J.B.; Steinkamp, J.A.; Tietjen, G.L.; Sebring, R.J. ); Oberdorster, G. )

    1991-01-01

    In order to obtain information about the particle redistribution phenomenon following the deposition of inhaled particles, as well as to obtain information about some of the mechanisms that may be operable in the redistribution of particles, lavaged lung free cell analyses and transmission electron microscopic (TEM) analyses of lung tissue and were performed using lungs from rats after they were subchronically exposed to aerosolized dioxide (TiO{sub 2}). TEM analyses indicated that the in situ autolysis of particle-containing Alveolar Macropages (AM) is one important mechanism involved in the redistribution of particles. Evidence was also obtained that indicated that the engulfment of one particle-containing phagocyte by another phagocyte also occurs. Another prominent mechanism of the particle redistribution phenomenon may be the in situ proliferation of particle-laden AM. We used the macrophage cell line J774A.1 as a surrogate for AM to investigate how different particulate loads in macrophages may affect their abilities to proliferate. These in vitro investigations indicated that the normal rate of proliferation of macrophages is essentially unaffected by the containment of relatively high particulate burdens. Overall, the results of our investigations suggest that in situ autolysis of particle-containing AM and the rephagocytosis of freed particles by other phagocytes, the phagocytosis of effete and disintegrating particle-containing phagocytes by other AM, and the in situ division of particle-containing AM are likely mechanisms that underlie the post-depositional redistribution of particles among the lung's AM during alveolar phase clearance. 19 refs., 8 figs., 2 tabs.

  7. Recent advances in alveolar biology: evolution and function of alveolar proteins.

    PubMed

    Orgeig, Sandra; Hiemstra, Pieter S; Veldhuizen, Edwin J A; Casals, Cristina; Clark, Howard W; Haczku, Angela; Knudsen, Lars; Possmayer, Fred

    2010-08-31

    This review is focused on the evolution and function of alveolar proteins. The lung faces physical and environmental challenges, due to changing pressures/volumes and foreign pathogens, respectively. The pulmonary surfactant system is integral in protecting the lung from these challenges via two groups of surfactant proteins - the small molecular weight hydrophobic SPs, SP-B and -C, that regulate interfacial adsorption of the lipids, and the large hydrophilic SPs, SP-A and -D, which are surfactant collectins capable of inhibiting foreign pathogens. Further aiding pulmonary host defence are non-surfactant collectins and antimicrobial peptides that are expressed across the biological kingdoms. Linking to the first symposium session, which emphasised molecular structure and biophysical function of surfactant lipids and proteins, this review begins with a discussion of the role of temperature and hydrostatic pressure in shaping the evolution of SP-C in mammals. Transitioning to the role of the alveolus in innate host defence we discuss the structure, function and regulation of antimicrobial peptides, the defensins and cathelicidins. We describe the recent discovery of novel avian collectins and provide evidence for their role in preventing influenza infection. This is followed by discussions of the roles of SP-A and SP-D in mediating host defence at the alveolar surface and in mediating inflammation and the allergic response of the airways. Finally we discuss the use of animal models of lung disease including knockouts to develop an understanding of the role of these proteins in initiating and/or perpetuating disease with the aim of developing new therapeutic strategies. PMID:20433956

  8. Alveolar macrophage kinetics and function after interruption of canine marrow function

    SciTech Connect

    Springmeyer, S.C.; Altman, L.C.; Kopecky, K.J.; Deeg, H.J.; Storb, R.

    1982-03-01

    To study the kinetics and function of alveolar macrophages after interruption of marrow function, we performed serial bronchoalveolar lavages in dogs. The studies were performed before and after 9.0 to 9.5 Grey total body irradiation and marrow infusion. Monocytes had disappeared from the bloodstream by Day 7 after the irradiation. Alveolar macrophages were significantly decreased at Day 21. At Days 14 and 21 myeloperoxidase-positive alveolar macrophages were also significantly decreased. Beyond Day 30 the number of circulating monocytes, myeloperoxidase-positive and total alveolar macrophages had returned. Sex chromatin stains of alveolar macrophages obtained from a male dog that received female marrow indicated that the repopulating macrophages were of marrow origin. In vitro studies of alveolar macrophage migration and phagocytosis demonstrated increased activities beyond Day 30. These studies suggest that in this model the alveolar macrophage is dependent on the bone marrow for support and that the alveolar macrophage depletion may impair lung defense mechanisms.

  9. Alveolar recruitment in pulmonary contusion: case report and literature review.

    PubMed

    Trindade, Lívia Maria Vitório; Lopes, Lucianne Cristina da Silva; Cipriano, Graziella França Bernardelli; Vendrame, Letícia Sandre; Andrade Junior, Ary

    2009-03-01

    Treatment of pulmonary contusion when adequately established is very simple in most cases. Pathophysiological changes occur as a result of the effects produced by loss of chest wall integrity, accumulation of fluid in the pleural cavity, obstruction of the airways and lung dysfunction. The alveolar recruitment maneuver is the reopening of collapsed lung areas by increasing inspiratory pressure in the airway. The primary objective of this case report was to evaluate the effectiveness of the alveolar recruitment maneuver in a patient with pulmonary contusion. A 33 year old male patient, with a clinical condition of bilateral chest trauma and traumatic brain injury, evolved with reduction of the level of consciousness, acute respiratory failure, hypovolemic shock and hemoptysis. The patient underwent thoracentesis, bilateral thoracic drainage and was also submitted to invasive mechanical ventilation. After 48 hours of invasive mechanical ventilation, in accordance with protective strategy an alveolar recruitment maneuver mode, pressure-controlled ventilation, pressure controlled 10 cmH2O, respiratory rate 10 rpm, inspiratory time 3.0, positive end-expiratory pressure 30 cmH2O and FI0(2) 100%, for two minutes. After the alveolar recruitment maneuver, the patient presented clinical pulmonary improvement, but there was a variation of 185 to 322 of Pa0(2)/FiO2 (arterial partial pressure of oxygen/ fraction of inspired oxygen). He was discharged from the intensive care unit 22 days after admission. The alveolar recruitment maneuver in this patient showed significant results in the treatment of pulmonary contusion, improving blood oxygenation, preventing alveolar collapse and reversing atelectasis. PMID:25303136

  10. Metabolic enhancement and increase of alveolar macrophages induced by ozone

    SciTech Connect

    Mochitate, K.; Miura, T.

    1989-06-01

    Male Wistar rats were exposed to 0.2 ppm ozone (O3) for 14 days and at intervals alveolar macrophages were collected by bronchoalveolar lavage to examine the effects of O3. The specific activities of glucose-6-phosphate dehydrogenase and glutathione peroxidase of alveolar macrophages increased to 1.6-fold (on the 3rd day) and 1.5-fold (on the 5th day), respectively, those of the control values. Similarly, the specific activities of pyruvate kinase, lactate dehydrogenase, and hexokinase also increased to 1.6-fold, 1.4-fold, and 1.2-fold, respectively, those of the control values on the 3rd day. The activities of all enzymes tested were maintained at significantly higher levels until the 14th day. Furthermore, the incorporation of (14C)thymidine into alveolar macrophages increased twice the control values on the 1st and 3rd days and was almost completely inhibited by the addition of 1.23 x 10(-4) M aphidicolin, a competitive inhibitor of DNA polymerase alpha. The number of alveolar macrophages collected from exposed animals also increased to 1.5-fold that of the control value on the 3rd day and was maintained at significantly higher level until the 14th day. It was noted that alveolar macrophages of small size preferentially increased between the 5th and 14th days. These results show that exposures to 0.2 ppm O3 induced a metabolic enhancement of the peroxidative metabolism, glycolysis, and DNA synthesis in alveolar macrophages and increased the macrophages of small size.

  11. Purification and properties of rabbit alveolar macrophage lysozyme.

    PubMed Central

    Carroll, S F; Martinez, R J

    1979-01-01

    Lysozyme was isolated from Bacillus Calmette-Guerin-elicited rabbit alveolar macrophages by acid extraction and purified to homogeneity by a single-column procedure. Yields of the purified enzyme averaged between 20 and 30 mg per rabbit, values far in excess of those obtained with previously published methods. Rabbit lysozyme has a molecular weight of 14,300 and exhibits optimal lytic activity against Micrococcus lysodeikticus at an ionic strength of 0.04, pH 6.5. Our results indicate that lysozyme and other granule components can be fractionated from elicited alveolar macrophages by using simple techniques, suggesting methods for the bulk purification of lysosomal constituents. Images PMID:37167

  12. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma

    PubMed Central

    Lopez, Jose Ignacio

    2016-01-01

    A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation. PMID:27158455

  13. Partial pulmonary embolization disrupts alveolarization in fetal sheep

    PubMed Central

    2010-01-01

    Background Although bronchopulmonary dysplasia is closely associated with an arrest of alveolar development and pulmonary capillary dysplasia, it is unknown whether these two features are causally related. To investigate the relationship between pulmonary capillaries and alveolar formation, we partially embolized the pulmonary capillary bed. Methods Partial pulmonary embolization (PPE) was induced in chronically catheterized fetal sheep by injection of microspheres into the left pulmonary artery for 1 day (1d PPE; 115d gestational age; GA) or 5 days (5d PPE; 110-115d GA). Control fetuses received vehicle injections. Lung morphology, secondary septal crests, elastin, collagen, myofibroblast, PECAM1 and HIF1α abundance and localization were determined histologically. VEGF-A, Flk-1, PDGF-A and PDGF-Rα mRNA levels were measured using real-time PCR. Results At 130d GA (term ~147d), in embolized regions of the lung the percentage of lung occupied by tissue was increased from 29 ± 1% in controls to 35 ± 1% in 1d PPE and 44 ± 1% in 5d PPE fetuses (p < 0.001). Secondary septal crest density was reduced from 8 ± 0% in controls to 5 ± 0% in 1d PPE and 4 ± 0% in 5d PPE fetuses (p < 0.05), indicating impaired alveolar formation. The deposition of differentiated myofibroblasts (23 ± 1% vs 28 ± 1%; p < 0.001) and elastin fibres (3 ± 0% vs 4 ± 0%; p < 0.05) were also impaired in embolized lung regions of PPE fetuses compared to controls. PPE did not alter the deposition of collagen or PECAM1. At 116d GA in 5d PPE fetuses, markers of hypoxia indicated that a small and transient hypoxic event had occurred (hypoxia in 6.7 ± 1.4% of the tissue within embolized regions of 5d PPE fetuses at 116d compared to 0.8 ± 0.2% of tissue in control regions). There was no change in the proportion of tissue labelled with HIF1α. There was no change in mRNA levels of the angiogenic factors VEGF and Flk-1, although a small increase in PDGF-Rα expression at 116d GA, from 1.00 ± 0.12 in

  14. Mandibular osteotomies after drawing out the inferior alveolar nerve along the canal.

    PubMed

    Jin, Hoon; Kim, Byung-Gun

    2003-01-01

    In some cases, the inferior alveolar nerve runs through a lower course than usual. In such cases, osteotomy of the mandible can injure the inferior alveolar nerves. In other instances, the course of the mandibular osteotomy can meet that of the inferior alveolar nerve. In these cases, a useful method may be excavating the canal and drawing the nerve out through it. With this technique, we can make the osteotomy as initially planned with minimal damage to the inferior alveolar nerve. PMID:14629066

  15. Ozone Minimums, 1979 to 2013

    NASA Video Gallery

    Minimum concentration of ozone in the southern hemisphere for each year from 1979-2013 (there is no data from 1995). Each image is the day of the year with the lowest concentration of ozone. A grap...

  16. Safe Minimum Internal Temperature Chart

    MedlinePlus

    ... JSR 286) Actions ${title} Loading... Safe Minimum Internal Temperature Chart Safe steps in food handling, cooking, and ... from other foods. Cook —Cook to the right temperature. Chill —Refrigerate food promptly. Cook all food to ...

  17. 2013 Arctic Sea Ice Minimum

    NASA Video Gallery

    After an unusually cold summer in the northernmost latitudes, Arctic sea ice appears to have reached its annual minimum summer extent for 2013 on Sept. 13, the NASA-supported National Snow and Ice ...

  18. Arctic Sea Ice Minimum, 2015

    NASA Video Gallery

    This animation shows the evolution of the Arctic sea ice cover from its wintertime maximum extent, which was reached on Feb. 25, 2015, and was the lowest on record, to its apparent yearly minimum, ...

  19. Minimum Principles in Motor Control.

    PubMed

    Engelbrecht, Sascha E.

    2001-06-01

    Minimum (or minimal) principles are mathematical laws that were first used in physics: Hamilton's principle and Fermat's principle of least time are two famous example. In the past decade, a number of motor control theories have been proposed that are formally of the same kind as the minimum principles of physics, and some of these have been quite successful at predicting motor performance in a variety of tasks. The present paper provides a comprehensive review of this work. Particular attention is given to the relation between minimum theories in motor control and those used in other disciplines. Other issues around which the review is organized include: (1) the relation between minimum principles and structural models of motor planning and motor control, (2) the empirically-driven development of minimum principles and the danger of circular theorizing, and (3) the design of critical tests for minimum theories. Some perspectives for future research are discussed in the concluding section of the paper. Copyright 2001 Academic Press. PMID:11401453

  20. Serial bronchoscopic lung lavage in pulmonary alveolar proteinosis under local anesthesia.

    PubMed

    Davis, K Rennis; Vadakkan, D Thomas; Krishnakumar, E V; Anas, A Muhammed

    2015-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. Mainstay of treatment is whole lung lavage, which requires general anesthesia. Herein, we report a case of primary PAP, successfully treated with serial bronchoscopic lung lavages under local anesthesia. PMID:25814803

  1. Breast metastasis in an adult woman with alveolar rhabdomyosarcoma of the ethmoid sinus

    PubMed Central

    Raj, Sean D.; Raj, Karuna M.; Krishnamurthy, Savitri; Brahmaroutu, Ashrita; Whitman, Gary J.

    2015-01-01

    A new breast mass was identified in an adult woman undergoing treatment for a known ethmoid sinus alveolar rhabdomyosarcoma. Histopathological evaluation revealed alveolar rhabdomyosarcoma metastatic to the breast. Alveolar rhabdomyosarcoma, primarily described in adolescents and especially rare in adults, can uncommonly metastasize to the breast. PMID:27186248

  2. Differential influence of propofol and isoflurane anesthesia in a non-human primate on the brain kinetics and binding of [(18)F]DPA-714, a positron emission tomography imaging marker of glial activation.

    PubMed

    Saba, Wadad; Goutal, Sébastien; Kuhnast, Bertrand; Dollé, Frédéric; Auvity, Sylvain; Fontyn, Yoan; Cayla, Jérôme; Peyronneau, Marie-Anne; Valette, Héric; Tournier, Nicolas

    2015-07-01

    Translocator protein 18 kDa (TSPO) expression at the mitochondrial membrane of glial cells is related to glial activation. TSPO radioligands such as [(18)F]DPA-714 are useful for the non-invasive study of neuroimmune processes using positron emission tomography (PET). Anesthetic agents were shown to impact mitochondrial function and may influence [(18)F]DPA-714 binding parameters and PET kinetics. [(18) F]DPA-714 PET imaging was performed in Papio anubis baboons anesthetized using either intravenous propofol (n = 3) or inhaled isoflurane (n = 3). Brain kinetics and metabolite-corrected input function were measured to estimate [(18) F]DPA-714 brain distribution (VT). Displacement experiments were performed using PK11195 (1.5 mg/kg). In vitro [(18)F]DPA-714 binding experiments were performed using baboon brain tissue in the absence and presence of tested anesthetics. Brain radioactivity peaked higher in isoflurane-anesthetized animals compared with propofol (SUVmax = 2.7 ± 0.5 vs. 1.3 ± 0.2, respectively) but was not different after 30 min. Brain VT was not different under propofol and isoflurane. Displacement resulted in a 35.8 ± 8.4% decrease of brain radioactivity under propofol but not under isoflurane (0.1 ± 7.0%). In vitro, the presence of propofol increased TSPO density and dramatically reduced its affinity for [(18)F]DPA-714 compared with control. This in vitro effect was not significant with isoflurane. Exposure to propofol and isoflurane differentially influences TSPO interaction with its specific radioligand [(18)F]DPA-714 with subsequent impact on its tissue kinetics and specific binding estimated in vivo using PET. Therefore, the choice of anesthetics and their potential influence on PET data should be considered for the design of imaging studies using TSPO radioligands, especially in a translational research context. PMID:25962575

  3. The volatile anesthetic isoflurane differentially suppresses the induction of erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice in an hypoxia-inducible factor-2-dependent manner.

    PubMed

    Kai, Shinichi; Tanaka, Tomoharu; Matsuyama, Tomonori; Suzuki, Kengo; Hirota, Kiichi

    2014-06-01

    Erythropoietin (EPO) is a glycoprotein hormone essential for the regulation of erythroid homeostasis. Although EPO production is prominent in the kidney and liver, its production in the central nervous system has also been detected. Tissue hypoxia due to systemic or local hypoxemia and acute anemia due to blood loss occurs frequently during various clinical settings, leading to a high possibility of elevated plasma EPO levels. However, it is largely unknown whether volatile anesthetic agents affect EPO production elicited by acute hypoxia in vivo. Male C57BL/6N CrSlc mice were exposed to a hypoxic insult as a result of bleeding-related anemia or hypoxemia while they were under anesthetized using various concentrations of isoflurane. EPO protein concentrations were assessed by enzyme-linked immunosorbent assay and mRNA levels were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. Plasma EPO concentration was induced as early as 3h following acute anemic and hypoxemic hypoxia and suppressed by clinically relevant doses of isoflurane in a dose-dependent manner. Anemic hypoxia induced EPO mRNA and protein synthesis in the kidney. In the kidney, isoflurane inhibited EPO induction caused by anemia but not that caused by hypoxemia. On the other hand, in the brain hypoxemia-induced EPO production was suppressed by isoflurane. Finally, qRT-PCR studies demonstrate that isoflurane differentially inhibit HIF-1α and HIF-2α mRNA expression in brain and kidney, indicating the involvement of HIF-2 in the hypoxia-induced EPO expression and inhibition of the induction by isoflurane. PMID:24680923

  4. Changes in pulse pressure variation and plethysmographic variability index caused by hypotension-inducing hemorrhage followed by volume replacement in isoflurane-anesthetized dogs.

    PubMed

    Klein, Adriana V; Teixeira-Neto, Francisco J; Garofalo, Natache A; Lagos-Carvajal, Angie P; Diniz, Miriely S; Becerra-Velásquez, Diana R

    2016-03-01

    OBJECTIVE To compare changes in pulse pressure variation (PPV) and plethysmographic variability index (PVI) induced by hemorrhage followed by volume replacement (VR) in isoflurane-anesthetized dogs. ANIMALS 7 healthy adult dogs. PROCEDURE Each dog was anesthetized with isoflurane and mechanically ventilated. End-tidal isoflurane concentration was adjusted to maintain mean arterial pressure (MAP) at 60 to 70 mm Hg before hemorrhage. Controlled hemorrhage was initiated and continued until the MAP decreased to 40 to 50 mm Hg, then autologous blood removed during hemorrhage was retransfused during VR. Various physiologic variables including PPV and PVI were recorded immediately before (baseline) and after controlled hemorrhage and immediately after VR. RESULTS Mean ± SD PPV and PVI were significantly increased from baseline after hemorrhage (PPV, 20 ± 6%; PVI, 18 ± 4%). After VR, the mean PPV (7 ± 3%) returned to a value similar to baseline, whereas the mean PVI (10 ± 3%) was significantly lower than that at baseline. Cardiac index (CI) and stroke index (SI) were significantly decreased from baseline after hemorrhage (CI, 2.07 ± 0.26 L/min/m(2); SI, 20 ± 3 mL/beat/m(2)) and returned to values similar to baseline after VR (CI, 4.25 ± 0.63 L/min/m(2); SI, 36 ± 6 mL/beat/m(2)). There was a significant positive correlation (r(2) = 0.77) between PPV and PVI after hemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that both PPV and PVI may be useful for identification of dogs that respond to VR with increases in SI and CI (ie, dogs in the preload-dependent limb of the Frank-Starling curve). PMID:26919599

  5. Role of nitric oxide-containing factors in the ventilatory and cardiovascular responses elicited by hypoxic challenge in isoflurane-anesthetized rats

    PubMed Central

    Mendoza, James P.; Passafaro, Rachael J.; Baby, Santhosh M.; Young, Alex P.; Bates, James N.; Gaston, Benjamin

    2014-01-01

    Exposure to hypoxia elicits changes in mean arterial blood pressure (MAP), heart rate, and frequency of breathing (fr). The objective of this study was to determine the role of nitric oxide (NO) in the cardiovascular and ventilatory responses elicited by brief exposures to hypoxia in isoflurane-anesthetized rats. The rats were instrumented to record MAP, heart rate, and fr and then exposed to 90 s episodes of hypoxia (10% O2, 90% N2) before and after injection of vehicle, the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME), or the inactive enantiomer d-NAME (both at 50 μmol/kg iv). Each episode of hypoxia elicited a decrease in MAP, bidirectional changes in heart rate (initial increase and then a decrease), and an increase in fr. These responses were similar before and after injection of vehicle or d-NAME. In contrast, the hypoxia-induced decreases in MAP were attenuated after administration of l-NAME. The initial increases in heart rate during hypoxia were amplified whereas the subsequent decreases in heart rate were attenuated in l-NAME-treated rats. Finally, the hypoxia-induced increases in fr were virtually identical before and after administration of l-NAME. These findings suggest that NO factors play a vital role in the expression of the cardiovascular but not the ventilatory responses elicited by brief episodes of hypoxia in isoflurane-anesthetized rats. Based on existing evidence that NO factors play a vital role in carotid body and central responses to hypoxia in conscious rats, our findings raise the novel possibility that isoflurane blunts this NO-dependent signaling. PMID:24744389

  6. Modulation of a recombinant invertebrate γ-aminobutyric acid receptor-chloride channel complex by isoflurane: effects of a point mutation in the M2 domain

    PubMed Central

    Edwards, Michelle D; Lees, George

    1997-01-01

    Inhalational anaesthetics modulate ligand-gated ion channels at clinical concentrations. In this paper we address submolecular mechanisms for γ-aminobutyric acid (GABA) receptor modulation by isoflurane. Wild-type Drosophila melanogaster homo-oligomeric GABA receptors were characterized and compared with an ion-channel mutant (alanine substituted to a serine in M2) by means of two-electrode voltage-clamp in membrane-invariant Xenopus oocytes. Both channel receptor isoforms generated outwardly rectifying, bicuculline-insensitive currents with reversal potentials characteristic of a chloride current. As previously shown, the point mutation in the M2 domain conferred a profound resistance to the blocking action of 10 μM picrotoxinin (PTX): circa 7 fold reduction at the GABA EC20. Isoflurane, 195–389 μM, enhanced GABA conductance in both receptor variants by significantly increasing the affinity of the agonist for its receptor without changing Hill slope or maximal response. Relative potencies were statistically indistinguishable. Isoflurane concentration-response curves (on circa GABA EC25) demonstrated that enhancement was effected at around 100–195 μM for both receptor subtypes, but a dramatic divergence was evident at concentrations above 400 μM: wild-type receptors exhibited concentration-dependent block, whilst mutant conductances continued to increase over the same concentration range, showing no tendency to saturate (up to 3330 μM). The above divergence was not attributable to differential desensitization: neither wild-type nor mutant conductance desensitized significantly (P>0.05) in the absence or presence of anaesthetic. This work demonstrates that modulatory sites for anaesthetic are present on a relatively primitive insect ion channel. The depression of GABA response at high isoflurane concentrations, in WT receptors, (typical of a variety of anaesthetic agents) may reflect low affinity channel block via the PTX site. The non

  7. Granulocyte macrophage colony stimulating factor therapy for pulmonary alveolar proteinosis.

    PubMed

    Shende, Ruchira P; Sampat, Bhavin K; Prabhudesai, Pralhad; Kulkarni, Satish

    2013-03-01

    We report a case of 58 year old female diagnosed with Pulmonary Alveolar Proteinosis (PAP) with recurrence of PAP after 5 repeated whole lung lavage, responding to subcutaneous injections of Granulocyte Macrophage Colony Stimulating Factor therapy (GM-CSF). Thus indicating that GM-CSF therapy is a promising alternative in those requiring repeated whole lung lavage PMID:24475687

  8. Immune dysregulation in the pathogenesis of pulmonary alveolar proteinosis.

    PubMed

    Martinez-Moczygemba, Margarita; Huston, David P

    2010-09-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease of the lung characterized by the accumulation of surfactant-derived lipoproteins within pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and increased infections. The disease is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. The underlying molecular mechanisms causing deficiencies in GM-CSF signaling are as follows: 1) high levels of neutralizing GM-CSF autoantibodies observed in autoimmune PAP; 2) mutations in CSF2RA, the gene encoding the alpha chain of the GM-CSF receptor, observed in hereditary PAP; and 3) reduced numbers and function of alveolar macrophages as a result of other clinical diseases seen in secondary PAP. Recent studies investigating the biology of GM-CSF have revealed that not only does this cytokine have an indispensable role in lung physiology, but it is also a critical regulator of innate immunity and lung host defense. PMID:20623372

  9. Evaluation of color Doppler ultrasonography in diagnosing hepatic alveolar echinococcosis.

    PubMed

    Tao, Song; Qin, Zhao; Haitao, Li; Lei, Yang; Lanhui, Yao; Qin, Xu; Yongquan, Lu; Hao, Wen

    2012-02-01

    To assess the accuracy of color Doppler ultrasonography in diagnosing hepatic alveolar echinococcosis, 129 patients were examined at the First Affiliated Hospital of Xinjiang Medical University between July 2004 and June 2010. Those patients suspected of having hepatic alveolar echinococcosis were examined and diagnosed by color Doppler ultrasound. All the cases were compared with the gold standard. The findings of their sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and 95% confidence interval were recorded. Sensitivity: 95% (95% confidence interval: 90.7%-99.3%); specificity: 20.7% (95% confidence interval: 6.0%-35.4%); positive predictive value: 80.5%; negative predictive value: 54.5%; positive likelihood ratio: 1.2: negative likelihood ratio: 0.2. Our study indicates that color Doppler ultrasonography, when used in diagnosing hepatic alveolar echinococcosis, has high sensitivity although specificity is low. Color Doppler ultrasound is, thus, considered to be an efficient means for diagnosing hepatic alveolar echinococcosis. PMID:22230130

  10. EVALUATION OF TRACE-ELEMENT INTERACTIONS USING CULTURED ALVEOLAR MACROPHAGES

    EPA Science Inventory

    It is important to consider the interactions of toxic trace elements in an evaluation of the toxicity of environmental pollutants. The in vitro toxicity screening system, using the rabbit alveolar macrophage, provides a particularly useful system for evaluating trace-element inte...

  11. Abnormal gallium scintigraphy in pulmonary alveolar proteinosis (PAP)

    SciTech Connect

    Yeh, S.D.; White, D.A.; Stover-Pepe, D.E.; Caravelli, J.F.; Van Uitert, C.; Benua, R.S.

    1987-04-01

    A patient with medulloblastoma of the cerebellum developed dyspnea and hypoxemia. Pulmonary function tests showed decreased lung volume and diffusing capacity, while the chest radiographs initially showed only mild interstitial infiltrates. Repeated gallium scans showed diffuse lung uptake and diagnosis of pulmonary alveolar proteinosis was made by open lung biopsy.

  12. The development and plasticity of alveolar type 1 cells.

    PubMed

    Yang, Jun; Hernandez, Belinda J; Martinez Alanis, Denise; Narvaez del Pilar, Odemaris; Vila-Ellis, Lisandra; Akiyama, Haruhiko; Evans, Scott E; Ostrin, Edwin J; Chen, Jichao

    2016-01-01

    Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth. PMID:26586225

  13. Studying the Role of Alveolar Macrophages in Breast Cancer Metastasis.

    PubMed

    Vadrevu, Surya Kumari; Sharma, Sharad; Chintala, Navin; Patel, Jalpa; Karbowniczek, Magdalena; Markiewski, Maciej

    2016-01-01

    This paper describes the application of the syngeneic model of breast cancer (4T1) to the studies on a role of pulmonary alveolar macrophages in cancer metastasis. The 4T1 cells expressing GFP in combination with imaging and confocal microscopy are used to monitor tumor growth, track metastasizing tumor cells, and quantify the metastatic burden. These approaches are supplemented by digital histopathology that allows the automated and unbiased quantification of metastases. In this method the routinely prepared histological lung sections, which are stained with hematoxylin and eosin, are scanned and converted to the digital slides that are then analyzed by the self-trained pattern recognition software. In addition, we describe the flow cytometry approaches with the use of multiple cell surface markers to identify alveolar macrophages in the lungs. To determine impact of alveolar macrophages on metastases and antitumor immunity these cells are depleted with the clodronate-containing liposomes administrated intranasally to tumor-bearing mice. This approach leads to the specific and efficient depletion of this cell population as confirmed by flow cytometry. Tumor volumes and lung metastases are evaluated in mice depleted of alveolar macrophages, to determine the role of these cells in the metastatic progression of breast cancer. PMID:27403530

  14. Increased alveolar soluble annexin V promotes lung inflammation and fibrosis.

    PubMed

    Buckley, Susan; Shi, Wei; Xu, Wei; Frey, Mark R; Moats, Rex; Pardo, Annie; Selman, Moises; Warburton, David

    2015-11-01

    The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesised that alveolar soluble annexin V contributes to lung fibrosis, based on the observation that human IPF bronchoalveolar lavage fluid (BALF) containing high annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when annexin V was depleted from the BALF. Conditioned medium from annexin V-treated alveolar epithelial type 2 cells (AEC2), but not annexin V per se, induced proliferation of human fibroblasts and contained pro-fibrotic, IPF-associated proteins, as well as pro-inflammatory cytokines that were found to correlate tightly (r>0.95) with annexin V levels in human BALF. ErbB2 receptor tyrosine kinase in AECs was activated by annexin V, and blockade reduced the fibrotic potential of annexin V-treated AEC-conditioned medium. In vivo, aerosol delivery of annexin V to mouse lung induced inflammation, fibrosis and increased hydroxyproline, with activation of Wnt, transforming growth factor-β, mitogen-activated protein kinase and nuclear factor-κB signalling pathways, as seen in IPF. Chronically increased alveolar annexin V levels, as reflected in increased IPF BALF levels, may contribute to the progression of IPF by inducing the release of pro-fibrotic mediators. PMID:26160872

  15. Biomimetics of fetal alveolar flow phenomena using microfluidics.

    PubMed

    Tenenbaum-Katan, Janna; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josué

    2015-01-01

    At the onset of life in utero, the respiratory system begins as a liquid-filled tubular organ and undergoes significant morphological changes during fetal development towards establishing a respiratory organ optimized for gas exchange. As airspace morphology evolves, respiratory alveolar flows have been hypothesized to exhibit evolving flow patterns. In the present study, we have investigated flow topologies during increasing phases of embryonic life within an anatomically inspired microfluidic device, reproducing real-scale features of fetal airways representative of three distinct phases of in utero gestation. Micro-particle image velocimetry measurements, supported by computational fluid dynamics simulations, reveal distinct respiratory alveolar flow patterns throughout different stages of fetal life. While attached, streamlined flows characterize the shallow structures of premature alveoli indicative of the onset of saccular stage, separated recirculating vortex flows become the signature of developed and extruded alveoli characteristic of the advanced stages of fetal development. To further mimic physiological aspects of the cellular environment of developing airways, our biomimetic devices integrate an alveolar epithelium using the A549 cell line, recreating a confluent monolayer that produces pulmonary surfactant. Overall, our in vitro biomimetic fetal airways model delivers a robust and reliable platform combining key features of alveolar morphology, flow patterns, and physiological aspects of fetal lungs developing in utero. PMID:25759753

  16. Noninvasive assessment of alveolar microvascular recruitment in conscious nonsedated rats

    PubMed Central

    Yilmaz, Cuneyt; Dane, Dan M.; Ravikumar, Priya; Unger, Roger H.; Hsia, Connie C.W.

    2013-01-01

    Recruitment of alveolar microvascular reserves, assessed from the relationship between pulmonary diffusing capacity (DLCO) and perfusion (Q̇c), is critical to maintenance of arterial blood oxygenation. Leptin-resistant ZDF fatty diabetic (fa/fa) rats exhibit restricted cardiopulmonary physiology under anesthesia. To assess alveolar microvascular function in conscious, non-sedated, non-instrumented, and minimally restrained animals, we adapted a rebreathing technique to fa/fa and control non-diabetic (+/+) rats (4-5 and 7-11 mo old) at rest and mild spontaneous activity. Measurements included O2 uptake, lung volume, Q̇c, DLCO, membrane diffusing capacity (DMCO), capillary blood volume (Vc) and septal tissue-blood volume. In older fa/fa than +/+ animals, DLCO and DMCO at a given Q̇c were lower; Vc was reduced in proportion to Q̇c. Results demonstrate the consequences of alveolar microangiopathy in metabolic syndrome: lung volume restriction, reduced Q̇c, and elevated membrane resistance to diffusion. At a given Q̇c, DLCO is lower in rats and guinea pigs than dogs or humans, consistent with limited alveolar microvascular reserves in small animals. PMID:24100202

  17. Breastfeeding, lung volumes and alveolar size at school-age

    PubMed Central

    Dogaru, Cristian M; Narayanan, Manjith; Spycher, Ben D; Pescatore, Anina M; Owers-Bradley, John; Beardsmore, Caroline S; Silverman, Michael; Kuehni, Claudia E

    2015-01-01

    Background Previous studies found larger lung volumes at school-age in formerly breastfed children, with some studies suggesting an effect modification by maternal asthma. We wanted to explore this further in children who had undergone extensive lung function testing. The current study aimed to assess whether breastfeeding was associated with larger lung volumes and, if so, whether all compartments were affected. We also assessed association of breastfeeding with apparent diffusion coefficient (ADC), which measures freedom of gas diffusion in alveolar-acinar compartments and is a surrogate of alveolar dimensions. Additionally, we assessed whether these effects were modified by maternal asthma. Methods We analysed data from 111 children and young adults aged 11–21 years, who had participated in detailed lung function testing, including spirometry, plethysmography and measurement of ADC of 3Helium (3He) by MR. Information on breastfeeding came from questionnaires applied in early childhood (age 1–4 years). We determined the association between breastfeeding and these measurements using linear regression, controlling for potential confounders. Results We did not find significant evidence for an association between duration of breastfeeding and lung volumes or alveolar dimensions in the entire sample. In breastfed children of mothers with asthma, we observed larger lung volumes and larger average alveolar size than in non-breastfed children, but the differences did not reach significance levels. Conclusions Confirmation of effects of breastfeeding on lung volumes would have important implications for public health. Further investigations with larger sample sizes are warranted. PMID:26180638

  18. The outcome of intraoral onlay block bone grafts on alveolar ridge augmentations: A systematic review

    PubMed Central

    Aloy-Prósper, Amparo; Peñarrocha-Oltra, David; Peñarrocha-Diago, Maria A.

    2015-01-01

    Aim: The purpose of this study was to systematically review clinical studies examining the survival and success rates of implants placed with intraoral onlay autogenous bone grafts to answer the following question: do ridge augmentations procedures with intraoral onlay block bone grafts in conjunction with or prior to implant placement influence implant outcome when compared with a control group (guided bone regeneration, alveolar distraction, native bone or short dental implants.)? Material and Method: An electronic data banks and hand searching were used to find relevant articles on vertical and lateral augmentation procedures performed with intraoral onlay block bone grafts for dental implant therapy published up to October 2013. Publications in English, on human subjects, with a controlled study design –involving at least one group with defects treated with intraoral onlay block bone grafts, more than five patients and a minimum follow-up of 12 months after prosthetic loading were included. Two reviewers extracted the data. Results: A total of 6 studies met the inclusion criteria: 4 studies on horizontal augmentation and 2 studies on vertical augmentation. Intraoperative complications were not reported. Most common postsurgical complications included mainly mucosal dehiscences (4 studies), bone graft or membrane exposures (3 studies), complete failures of block grafts (2 studies) and neurosensory alterations (4 studies). For lateral augmentation procedures, implant survival rates ranged from 96.9% to 100%, while for vertical augmentation they ranged from 89.5% to 100%. None article studied the soft tissues healing. Conclusions: Survival and success rates of implants placed in horizontally and vertically resorbed edentulous ridges reconstructed with block bone grafts are similar to those of implants placed in native bone, in distracted sites or with guided bone regeneration. More surgical challenges and morbidity arise from vertical augmentations, thus short

  19. Use of alveolar cell monolayers of varying electrical resistance to measure pulmonary peptide transport.

    PubMed

    Dodoo, A N; Bansal, S S; Barlow, D J; Bennet, F; Hider, R C; Lansley, A B; Lawrence, M J; Marriott, C

    2000-02-01

    The apparent permeability coefficient (P(app)) of two fluorescently tagged model hydrophilic peptides, acXASNH(2) and acXAS(GAS)(7)NH(2), and (14)C-mannitol across monolayers of cultured rat alveolar epithelial cells of varying transepithelial electrical resistance (TER) has been examined. In line with their design features, the peptides were not degraded under the conditions of the test. Furthermore, no concentration dependence of transport of the tripeptide acXASNH(2) was observed over the concentration range studied, nor was any directional transport seen for either of the model peptides, indicating that under the conditions of the test they were not substrates for any transporters or efflux pumps. From the hydrophilic nature of the peptides (as assessed by their log P), and their inverse dependence of transport with molecular weight and TER, it was assumed that the peptides were transported across the cell monolayer passively via the paracellular route. The observed P(app) for the transport of (14)C-mannitol and the peptides across rat alveolar epithelial cell monolayers were found to be inversely (though not linearly) related to the measured TER and could be well-modeled assuming the presence of two populations of "pores" in the cell monolayer, namely, cylindrical pores of diameter 1.5 nm and large pores of diameter 20 nm. The relative populations of the two types of pores varied with the TER of the monolayer, with the number of large pores decreasing with an increase in TER (and the number of small pores taken as fixed). These results suggest that if the cell monolayer is well characterized with respect to the passage of a range of probe molecules across monolayers of varying electrical resistance, it should be possible to predict the P(app) of any hydrophilic peptide or drug crossing the membrane by the paracellular route at any desired TER using a monolayer of any electrical resistance, above a minimum value. PMID:10688751

  20. Hemodynamic stability, myocardial ischemia, and perioperative outcome after carotid surgery with remifentanil/propofol or isoflurane/fentanyl anesthesia.

    PubMed

    Jellish, W Scott; Sheikh, Taqdees; Baker, William H; Louie, Eric K; Slogoff, Stephen

    2003-07-01

    This study compares remifentanil/propofol (remi/prop) with isoflurane/fentanyl (iso/fen) anesthesia to determine which provides the greater hemodynamic stability, lesser myocardial ischemia, and morbidity with better postoperative outcomes after carotid endarterectomy. Sixty patients undergoing unilateral carotid endarterectomy were randomized to receive either a remi/prop or iso/fen anesthetic. Hemodynamic variables were recorded during the surgical procedure. In addition, transesophageal echocardiography was used to assess evidence of intraoperative regional wall motion abnormalities suggestive of cardiac ischemia. Emergence and extubation times, recovery from anesthesia, hemodynamic instability, nausea, vomiting, and pain in post anesthesia recovery, discharge delays, ICU admittance, hospital discharge, and preoperative and postoperative troponin levels were compared using appropriate statistical methods with P < 0.05 considered significant. The groups were demographically alike. Hemodynamic variables were similar during intubation and throughout surgery. Twenty-two percent of patients receiving iso/fen developed intraoperative regional wall motion abnormalities suggestive of ischemia, whereas no remi/prop patients had changes (P < 0.05). There was no difference in ST-T wave changes after surgery, and no patient had an elevation in troponin I levels. Postoperative variables were similar except that patients who received iso/fen had lower Stewart recovery scores during the first 15 minutes after post anesthesia care unit admission and a higher incidence of nausea and vomiting the day after surgery, whereas patients receiving remi/prop had discharge delays secondary to hypertension. ICU admittance, time to first void, oral intake, and time to hospital discharge were similar between the groups. At 9 times the cost of an iso/fen anesthesia technique, remi/prop offers little advantage over inhalational anesthesia for carotid endarterectomy. PMID:12826964

  1. Subdural Pressure and Brain Condition During Propofol Vs Isoflurane - Nitrous Oxide Anaesthesia in Patients Undergoing Elective Supratentorial Tumour Surgery

    PubMed Central

    Santra, Sankari; Das, Bibhukalyani

    2009-01-01

    Summary Total intravenous anaesthesia has received much importance than inhalational anaesthesia in neuroanaesthetic practice. In an effort to determine whether any important clinical differences occur, studies concerning intracranial pressure (ICP), degree of dural tension and degree of brain swelling during intravenous and inhalational based anaesthesia are warranted like the present one. A total of 68 patients were assigned randomly to one of two groups. In Group-I(n=34), anaesthesia was induced with propofol (1-3mg.kg−1) and maintained with propofol (6-10mg.kg−1.hr−1) and fentanyl (2-3mcg.kg−1.hr−1). In Group-II (n=34), anaesthesia was induced with propofol (1-3mg.kg−1) but maintained with isoflurane, nitrous oxide and fentanyl (2-3mcg.kg−1.hr−1). Moderate hypocapnia was applied to maintain arterial carbon dioxide around 30mmHg. Mean arterial blood pressure was stabilized with phenylephrine whenever necessary. Subdural intracranial pressure, mean arterial pressure, cerebral perfusion pressure were monitored before and after 10min period of hyperventilation. Furthermore, the tension of dura before and after of hyperventilation and the degree of brain swelling after opening of dura were also estimated by the neurosurgeon. No differences were found between the groups with regards to demographics, neuroradiologic diagnosis, position of head and time of ICP measurement. Before hyperventilation, both ICP and dural tension were significantly lower in Group I compared with Group-II (P<0.05). But after hyperventilation there was no significant difference of ICP and dural tension in between groups. The degree of brain swelling after opening of dura was similar in both groups. There was a positive correlation between measured ICP and brain swelling score. PMID:20640077

  2. Isoflurane reduces oxygen-glucose deprivation-induced oxidative, inflammatory, and apoptotic responses in H9c2 cardiomyocytes

    PubMed Central

    Liu, Jun; Yang, Shuangmei; Zhang, Xiaoran; Liu, Guoze; Yue, Xiuqin

    2016-01-01

    Isoflurane (ISO) protects the heart from hypoxia-reperfusion injury. However, the molecular mechanisms of ISO in oxygen-glucose deprivation (OGD)-induced H9c2 cardiomyocyte injury is yet to be understood. Using H9c2 cells cultured in vitro, we examined the cytotoxicity of different doses of ISO (0.7%, 1.4%, and 2.1%) to H9c2 cells and found that 2.1% ISO had significant toxicity to the cell. Thus, 1.4% ISO was selected for the subsequent experiments. ISO notably ameliorated cell viability loss, lactate dehydrogenase release, and creatine kinase activity of H9c2 cells that were treated with OGD. ISO suppressed OGD-induced pro-inflammatory tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8 production, and nuclear factor (NF)-κB activation in H9c2 cells. ISO reduced the reactive oxygen species and malondialdehyde generation, but it enhanced the superoxide dismutase activity in OGD-stimulated H9c2 cells. In addition, diminished OGD-induced cell apoptosis and preserved mitochondrial membrane potential were observed in ISO-treated H9c2 cells. ISO markedly up-regulated the anti-apoptotic Bcl-2 expression but inhibited the pro-apoptotic expressions of Bax, procaspase-3, cleaved caspase-3, and caspase-3 activity. Mechanistically, the cardioprotective effects of ISO on OGD-induced H9c2 cell injury were mediated by the Akt signaling pathway. These findings suggest that ISO alleviates OGD-induced H9c2 cell injury and may therefore be used to prevent and treat ischemic heart diseases. PMID:27398143

  3. Alveolar lining fluid regulates mononuclear phagocyte 5-lipoxygenase metabolism.

    PubMed

    Phare, S M; Peters-Golden, M; Coffey, M J

    1998-11-01

    The enzyme 5-lipoxygenase (5-LO) catalyses the synthesis of leukotrienes (LT), which are important in phagocytosis and killing of microorganisms. The alveolar macrophage (AM), the primary resident defender of the alveolar space, has a greater capacity for LT synthesis than its precursor, the peripheral blood monocyte (PBM). This study investigated whether the alveolar lining fluid (ALF) upregulates LT synthetic capacity in mononuclear phagocytes. Rat AM, peritoneal macrophages (PM) and ALF were obtained by lavage from pathogen-free animals. Human PBM were isolated from normal subjects. 5-LO metabolism and expression were measured with and without ALF. Rat ALF increased 5-LO metabolism (136.4+/-15.1% of control) in cultured PBM. This was associated with increased 5-LO activating protein (FLAP) (357+/-29.5 %), and 5-LO expression (188+/-31.3%). Culture of AM for 3 days resulted in a greater decrement in LTB4 synthesis (LTB4 15.4+/-6.9% of day 1) than in PM (54.7+/-8.3% of day 1), suggesting a greater dependence of AM 5-LO metabolism on ALF. 5-LO and FLAP expression decreased to a greater degree in AM than PM in culture. Furthermore, AM cultured with ALF maintained their LT synthetic capacity, FLAP and 5-LO expression compared with control cells cultured in medium alone. In conclusion, alveolar lining fluid increased 5-lipoxygenase metabolism in peripheral blood monocytes and maintained it in cultured alveolar macrophages, by a mechanism of increased 5-lipoxygenase and 5-lipoxygenase activating protein expression. This may boost host defence capabilities. PMID:9864011

  4. Immunosuppressive properties of surfactant and plasma on alveolar macrophages.

    PubMed

    Allen, J N; Moore, S A; Pope-Harman, A L; Marsh, C B; Wewers, M D

    1995-03-01

    Alveolar macrophages have been shown to be major producers of the potent proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha, and of the antiinflammatory cytokine interleukin-1 receptor antagonist. During the adult respiratory distress syndrome the normally surfactant-coated alveolus becomes flooded with plasma proteins, altering the milieu of alveolar cells such as alveolar macrophages. To understand alveolar macrophage function during the adult respiratory distress syndrome, the individual and combined effects of surfactant and plasma on alveolar macrophage cytokine production was examined. A synthetic surfactant (Exosurf) and a bovine-derived surfactant (Survanta) both inhibited production of interleukin-1 beta, pro-interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist in a dose-dependent manner. This inhibition was noted when both endotoxin and heat-killed Staphylococcus aureus were used as stimuli. Autologous plasma also inhibited interleukin-1 beta and tumor necrosis factor-alpha release in a dose-dependent manner, but, unlike surfactant, plasma did not inhibit interleukin-1 receptor antagonist release. Similarly, the combination of plasma and surfactant inhibited interleukin-1 beta and tumor necrosis factor-alpha release but not interleukin-1 receptor antagonist release. In support of these data, interleukin-1 receptor antagonist was detectable in five of six bronchoalveolar lavage fluid samples from patients with adult respiratory distress syndrome at a mean concentration of 465 pg/ml; on the other hand, interleukin-1 beta was not detectable in any of these samples. These results indicate that the relative production of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist can be altered depending on the local concentration of both surfactant and plasma. PMID:7897303

  5. N-acetylcysteine inhibits alveolar epithelial-mesenchymal transition

    PubMed Central

    Felton, V. M.; Borok, Z.

    2009-01-01

    The ability of transforming growth factor-β1 (TGF-β1) to induce epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AEC) in vitro and in vivo, together with the demonstration of EMT in biopsies of idiopathic pulmonary fibrosis (IPF) patients, suggests a role for TGF-β1-induced EMT in disease pathogenesis. We investigated the effects of N-acetylcysteine (NAC) on TGF-β1-induced EMT in a rat epithelial cell line (RLE-6TN) and in primary rat alveolar epithelial cells (AEC). RLE-6TN cells exposed to TGF-β1 for 5 days underwent EMT as evidenced by acquisition of a fibroblast-like morphology, downregulation of the epithelial-specific protein zonula occludens-1, and induction of the mesenchymal-specific proteins α-smooth muscle actin (α-SMA) and vimentin. These changes were inhibited by NAC, which also prevented Smad3 phosphorylation. Similarly, primary alveolar epithelial type II cells exposed to TGF-β1 also underwent EMT that was prevented by NAC. TGF-β1 decreased cellular GSH levels by 50–80%, whereas NAC restored them to ∼150% of those found in TGF-β1-treated cells. Treatment with glutathione monoethyl ester similarly prevented an increase in mesenchymal marker expression. Consistent with its role as an antioxidant and cellular redox stabilizer, NAC dramatically reduced intracellular reactive oxygen species production in the presence of TGF-β1. Finally, inhibition of intracellular ROS generation during TGF-β1 treatment prevented alveolar EMT, but treatment with H2O2 alone did not induce EMT. We conclude that NAC prevents EMT in AEC in vitro, at least in part through replenishment of intracellular GSH stores and limitation of TGF-β1-induced intracellular ROS generation. We speculate that beneficial effects of NAC on pulmonary function in IPF may be mediated by inhibitory effects on alveolar EMT. PMID:19648289

  6. N-acetylcysteine inhibits alveolar epithelial-mesenchymal transition.

    PubMed

    Felton, V M; Borok, Z; Willis, B C

    2009-11-01

    The ability of transforming growth factor-beta1 (TGF-beta1) to induce epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AEC) in vitro and in vivo, together with the demonstration of EMT in biopsies of idiopathic pulmonary fibrosis (IPF) patients, suggests a role for TGF-beta1-induced EMT in disease pathogenesis. We investigated the effects of N-acetylcysteine (NAC) on TGF-beta1-induced EMT in a rat epithelial cell line (RLE-6TN) and in primary rat alveolar epithelial cells (AEC). RLE-6TN cells exposed to TGF-beta1 for 5 days underwent EMT as evidenced by acquisition of a fibroblast-like morphology, downregulation of the epithelial-specific protein zonula occludens-1, and induction of the mesenchymal-specific proteins alpha-smooth muscle actin (alpha-SMA) and vimentin. These changes were inhibited by NAC, which also prevented Smad3 phosphorylation. Similarly, primary alveolar epithelial type II cells exposed to TGF-beta1 also underwent EMT that was prevented by NAC. TGF-beta1 decreased cellular GSH levels by 50-80%, whereas NAC restored them to approximately 150% of those found in TGF-beta1-treated cells. Treatment with glutathione monoethyl ester similarly prevented an increase in mesenchymal marker expression. Consistent with its role as an antioxidant and cellular redox stabilizer, NAC dramatically reduced intracellular reactive oxygen species production in the presence of TGF-beta1. Finally, inhibition of intracellular ROS generation during TGF-beta1 treatment prevented alveolar EMT, but treatment with H2O2 alone did not induce EMT. We conclude that NAC prevents EMT in AEC in vitro, at least in part through replenishment of intracellular GSH stores and limitation of TGF-beta1-induced intracellular ROS generation. We speculate that beneficial effects of NAC on pulmonary function in IPF may be mediated by inhibitory effects on alveolar EMT. PMID:19648289

  7. DA-Raf–dependent inhibition of the Ras-ERK signaling pathway in type 2 alveolar epithelial cells controls alveolar formation

    PubMed Central

    Watanabe-Takano, Haruko; Takano, Kazunori; Sakamoto, Akemi; Matsumoto, Kenji; Tokuhisa, Takeshi; Endo, Takeshi; Hatano, Masahiko

    2014-01-01

    Alveolar formation is coupled to the spatiotemporally regulated differentiation of alveolar myofibroblasts (AMYFs), which contribute to the morphological changes of interalveolar walls. Although the Ras-ERK signaling pathway is one of the key regulators for alveolar formation in developing lungs, the intrinsic molecular and cellular mechanisms underlying its role remain largely unknown. By analyzing the Ras-ERK signaling pathway during postnatal development of lungs, we have identified a critical role of DA-Raf1 (DA-Raf)—a dominant-negative antagonist for the Ras-ERK signaling pathway—in alveolar formation. DA-Raf–deficient mice displayed alveolar dysgenesis as a result of the blockade of AMYF differentiation. DA-Raf is predominantly expressed in type 2 alveolar epithelial cells (AEC2s) in developing lungs, and DA-Raf–dependent MEK1/2 inhibition in AEC2s suppresses expression of tissue inhibitor of matalloprotienase 4 (TIMP4), which prevents a subsequent proteolytic cascade matrix metalloproteinase (MMP)14–MMP2. Furthermore, MMP14–MMP2 proteolytic cascade regulates AMYF differentiation and alveolar formation. Therefore, DA-Raf–dependent inhibition of the Ras-ERK signaling pathway in AEC2s is required for alveolar formation via triggering MMP2 activation followed by AMYF differentiation. These findings reveal a pivotal role of the Ras-ERK signaling pathway in the dynamic regulation of alveolar development. PMID:24843139

  8. Development of pulmonary bronchiolo-alveolar adenocarcinomas in transgenic mice overexpressing murine c- myc and epidermal growth factor in alveolar type II pneumocytes

    PubMed Central

    Ehrhardt, A; Bartels, T; Geick, A; Klocke, R; Paul, D; Halter, R

    2001-01-01

    Transgenic mouse models were established to study tumorigenesis of bronchiolo-alveolar adenocarcinomas derived from alveolar type II pneumocytes (AT-II cells). Transgenic lines expressing the murine oncogene c- myc under the control of the lung-specific surfactant protein C promoter developed multifocal bronchiolo-alveolar hyperplasias, adenomas and carcinomas respectively, whereas transgenic lines expressing a secretable form of the epidermal growth factor (IgEGF), a structural and functional homologue of transforming growth factor α (TGFα), developed hyperplasias of the alveolar epithelium. Since the oncogenes c- myc and TGFα are frequently overexpressed in human lung bronchiolo-alveolar adenocarcinomas, these mouse lines are useful as models for human lung bronchiolo-alveolar adenocarcinomas. The average life expectancies of hemizygous and homozygous c- myc transgenics were 14.25 months and 9.2 months, respectively, suggesting that a dosage effect of c- myc caused an accelerated bronchiolo-alveolar adenocarcinoma formation. First analyses of double transgenics, hemizygous for both c- myc and IgEGF, show that these mice develop bronchiolo-alveolar adenocarcinomas at the average age of 9 months, indicating that these oncogenes cooperate during the lung cancer formation. Our results demonstrate that c- myc and EGF are directly involved and cooperate with one another during formation of bronchiolo-alveolar adenocarcinomas in the lung. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11259097

  9. ACSB: A minimum performance assessment

    NASA Technical Reports Server (NTRS)

    Jones, Lloyd Thomas; Kissick, William A.

    1988-01-01

    Amplitude companded sideband (ACSB) is a new modulation technique which uses a much smaller channel width than does conventional frequency modulation (FM). Among the requirements of a mobile communications system is adequate speech intelligibility. This paper explores this aspect of minimum required performance. First, the basic principles of ACSB are described, with emphasis on those features that affect speech quality. Second, the appropriate performance measures for ACSB are reviewed. Third, a subjective voice quality scoring method is used to determine the values of the performance measures that equate to the minimum level of intelligibility. It is assumed that the intelligibility of an FM system operating at 12 dB SINAD represents that minimum. It was determined that ACSB operating at 12 dB SINAD with an audio-to-pilot ratio of 10 dB provides approximately the same intelligibility as FM operating at 12 dB SINAD.

  10. The Maunder minimum: a revision

    NASA Astrophysics Data System (ADS)

    Zolotova, Nadezhda; Ponyavin, Dmitri

    2015-08-01

    One of the most enigmatic features of the solar history in the past was the Maunder minimum (1645-1715). We estimated the daily nominal sunspot counts of each observer individually from 1610 to 1720. Simultaneous comparison of textual reports, tables, and sunspot drawings reveals a significant difference between them. Some observers (among whom were Jean Picard and Giovanni Domenico Cassini, both from the Royal Observatory in Paris) systematically made gaps in reports when others noticed sunspots. Philippe de La Hire announced only fewer sunspot groups compared with the other observers. We argue that different points of view of observers of the seventeenth-century on the origin of sunspots resulted in strong underestimation of sunspot groups. Our findings suggest that the Maunder minimum was an ordinary secular minimum with reduced but non-stopped solar cyclicity.

  11. Secondary Alveolar Bone Grafting and Iliac Cancellous Bone Harvesting for Patients With Alveolar Cleft.

    PubMed

    Pan, Weiyi; Wu, Chenzhou; Yang, Zheng; Duan, Zexi; Su, Zhifei; Wang, Peiqi; Zheng, Qian; Li, Chunjie

    2016-06-01

    To assess the efficacy of present interventions optimizing the result of secondary alveolar bone grafting (SABG) and the interventions alleviating the donor site morbidity after iliac cancellous bone harvesting. Researches were identified by searching the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Chinese BioMedical Literature Database, and the China National Knowledge Infrastructure. In addition, relevant journals and references of the included studies were searched manually. The Oxford 2011 Levels of Evidence were applied to assess the methodological quality of selected studies, and the best evidence synthesis system was applied afterward to measure the strength of evidence. As a result, 42 studies were considered eligible and included, among which 4 were of high quality while 38 were of low quality. Thirty lines of evidences were acquired after the synthesis, among which 13 were rated as moderate while 17 were rated as insufficient. As for the interventions optimizing the result of SABG, moderate evidence confirmed the efficacy of preoperative orthodontic treatment, the superiority of performing SABG before the eruption of canine, and the accuracy of cone beam computed tomography in preoperative estimation of the cleft volume. As for the interventions alleviating the morbidity of iliac cancellous bone harvesting, moderate evidence confirmed the treatment benefit of the interventions below: minimally invasive technique, including trephine and Shepard osteotomy; preemptive analgesia, including continuous bupivacaine infusion or transversus abdominis plane block. As for the rest interventions, only insufficient evidence was found. PMID:27244214

  12. Phosphoproteome Profiling of SH-SY5y Neuroblastoma Cells Treated with Anesthetics: Sevoflurane and Isoflurane Affect the Phosphorylation of Proteins Involved in Cytoskeletal Regulation.

    PubMed

    Lee, Joomin; Ahn, Eunsook; Park, Wyun Kon; Park, Seyeon

    2016-01-01

    Inhalation anesthetics are used to decrease the spinal cord transmission of painful stimuli. However, the molecular or biochemical processes within cells that regulate anesthetic-induced responses at the cellular level are largely unknown. Here, we report the phosphoproteome profile of SH-SY5y human neuroblastoma cells treated with sevoflurane, a clinically used anesthetic. Phosphoproteins were isolated from cell lysates and analyzed using two-dimensional gel electrophoresis. The phosphorylation of putative anesthetic-responsive marker proteins was validated using western blot analysis in cells treated with both sevoflurane and isoflurane. A total of 25 phosphoproteins were identified as differentially phosphorylated proteins. These included key regulators that signal cytoskeletal remodeling steps in pathways related to vesicle trafficking, axonal growth, and cell migration. These proteins included the Rho GTPase, Ras-GAP SH3 binding protein, Rho GTPase activating protein, actin-related protein, and actin. Sevoflurane and isoflurane also resulted in the dissolution of F-actin fibers in SH-SY5y cells. Our results show that anesthetics affect the phosphorylation of proteins involved in cytoskeletal remodeling pathways. PMID:27611435

  13. On the Minimum Vocabulary Problem.

    ERIC Educational Resources Information Center

    Chandrasekharan, N.; And Others

    1987-01-01

    Demonstrates the use of a directed graph model as a tool for finding desirable minimum vocabularies to be used in indexing and information retrieval. The basic algorithm is outlined, possible enhancements to the model are discussed, and further research questions are suggested. (Author/CLB)

  14. 76 FR 11668 - Minimum Capital

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... Enterprises' future, FHFA is monitoring the activities of the Enterprises to: (a) Limit their risk and... 12 U.S.C. 4612(d). The 60-day comment period closed on April 9, 2010. See Federal Register 75 FR 6151... amended. See 74 FR 5597 (January 30, 2009). As a result, the definition of ``minimum capital level''...

  15. Tennessee Minimum School Bus Standards.

    ERIC Educational Resources Information Center

    Tennessee State Board of Education, 2004

    2004-01-01

    The School Bus Specifications and Procedures adopted by the 2000 National Conference on School Transportation and the Federal Motor Vehicle Safety Standards (FMVSS) were used as guides by the Tennessee State Board of Education Pupil Transportation Advisory Committee in developing the revised minimum specifications for school bus chassis and school…

  16. Equivalence to the Minimum Qualifications.

    ERIC Educational Resources Information Center

    California Community Colleges, Sacramento. Academic Senate.

    Assembly Bill (AB) 1725 provides for the hiring of faculty who do not meet the precise letter of the minimum qualifications, provided that the governing board of an institution determines that an applicant possesses qualifications that are at least equivalent. In order to make these determinations, each district must have and use an equivalency…

  17. Leukotriene B4 receptors on guinea pig alveolar eosinophils

    SciTech Connect

    Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P. )

    1991-09-01

    The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 {times} 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 {plus minus} 0.22 nM; Bmax1 = 966 {plus minus} 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 {plus minus} 8.9 nM; Bmax2 = 5557 {plus minus} 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of (3H)LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 {plus minus} 0.14 and 18.14 {plus minus} 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 {times} 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 {times} 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions.

  18. Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats.

    PubMed

    Wach, R; Emery, C J; Bee, D; Barer, G R

    1987-02-01

    The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection

  19. A novel 1,25-dihydroxyvitamin D-activin A pathway in human alveolar macrophages is dysfunctional in patients with pulmonary alveolar proteinosis (PAP).

    PubMed

    Barna, Barbara P; Malur, Anagha; Dalrymple, Heidi; Karnekar, Reema; Culver, Daniel A; Abraham, Susamma; Singh, Ravinder J; Brescia, Donald; Kavuru, Mani S; Thomassen, Mary Jane

    2009-01-01

    We have shown that activin A, a cytokine implicated in regulating B-cell proliferation, is severely deficient in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP), an autoimmune disorder characterized by surfactant accumulation and neutralizing autoantibodies to granulocyte-macrophage colony stimulating factor. Mechanisms of activin regulation in alveolar macrophages are not well understood. Based on previous gene array results from PAP bronchoalveolar lavage cells suggesting deficiencies in vitamin D target genes, and on recent evidence of vitamin D receptor elements (VDREs) in the human activin A gene promoter, we investigated the effects of 1,25-dihydroxyvitamin D (vitamin D(3)) on activin A expression in alveolar macrophages from healthy individuals and PAP patients. Activin A expression was stimulated by LPS in cultures of either healthy control or PAP alveolar macrophages; in contrast, vitamin D(3) increased activin A only in healthy controls but not in PAP. Compared to healthy controls, freshly obtained (uncultured) PAP alveolar macrophages displayed healthy intrinsic vitamin D receptor expression but deficient expression of vitamin D target genes, cathelicidin and thioredoxin interacting protein. PAP patients also demonstrated a relative insufficiency of circulating vitamin D. Investigation of activin A in murine alveolar macrophages confirmed a lack of functional response to vitamin D as anticipated since murine activin A does not contain VDREs. Results suggest that mechanisms of activin A deficiency in PAP alveolar macrophages may involve dysregulation of a novel species-specific vitamin D-activin A pathway. PMID:18803071

  20. Alveolar Type II Epithelial Cell Dysfunction in Rat Experimental Hepatopulmonary Syndrome (HPS)

    PubMed Central

    Yang, Wenli; Hu, Bingqian; Wu, Wei; Batra, Sachin; Blackburn, Michael R.; Alcorn, Joseph L.; Fallon, Michael B.; Zhang, Junlan

    2014-01-01

    The hepatopulmonary syndrome (HPS) develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2) play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D) which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL). We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064) induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target. PMID:25419825

  1. An automatic early stage alveolar-bone-resorption evaluation method on digital dental panoramic radiographs

    NASA Astrophysics Data System (ADS)

    Zhang, Min; Katsumata, Akitoshi; Muramatsu, Chisako; Hara, Takeshi; Suzuki, Hiroki; Fujita, Hiroshi

    2014-03-01

    Periodontal disease is a kind of typical dental diseases, which affects many adults. The presence of alveolar bone resorption, which can be observed from dental panoramic radiographs, is one of the most important signs of the progression of periodontal disease. Automatically evaluating alveolar-bone resorption is of important clinic meaning in dental radiology. The purpose of this study was to propose a novel system for automated alveolar-bone-resorption evaluation from digital dental panoramic radiographs for the first time. The proposed system enables visualization and quantitative evaluation of alveolar bone resorption degree surrounding the teeth. It has the following procedures: (1) pre-processing for a test image; (2) detection of tooth root apices with Gabor filter and curve fitting for the root apex line; (3) detection of features related with alveolar bone by using image phase congruency map and template matching and curving fitting for the alveolar line; (4) detection of occlusion line with selected Gabor filter; (5) finally, evaluation of the quantitative alveolar-bone-resorption degree in the area surrounding teeth by simply computing the average ratio of the height of the alveolar bone and the height of the teeth. The proposed scheme was applied to 30 patient cases of digital panoramic radiographs, with alveolar bone resorption of different stages. Our initial trial on these test cases indicates that the quantitative evaluation results are correlated with the alveolar-boneresorption degree, although the performance still needs further improvement. Therefore it has potential clinical practicability.

  2. Relationship of Anterior Alveolar Dimensions with Mandibular Divergence in Class I Malocclusion – A Cephalometric Study

    PubMed Central

    Korath, Vinoth Abraham; Nagachandran; Vijayalakshmi, Devaki; Parameswaran, Ratna; Raman, Priya; Sunitha, Catherine; Khan, Nayeemullah

    2016-01-01

    Introduction One of the major limiting factors in retraction of proclined teeth is the width of the alveolus both in maxilla and mandible. Aim The objective of this study was to assess the maxillary and mandibular anterior alveolar dimensions and to correlate with mandibular divergence in Class I bi-dento-alveolar protrusion patients. Materials and Methods Pretreatment lateral cephalograms (n=88) were analysed using a composite analysis with cephalometric software. Both maxillary and mandibular anterior alveolar widths and heights were measured and correlated with mandibular divergence. One-way analysis (ANOVA) and Pearson correlation test were used to compare and establish the significance between groups. Results Segregation of the data based on variation in the bi-cortical widths and heights showed that lesser alveolar widths and greater alveolar heights were associated with the high angled subjects and greater alveolar widths and lesser heights were associated with low angled subjects. Conclusion Patients with hyperdivergent mandible exhibited thin anterior alveolar width and greater alveolar height whereas low angled subjects had wider alveolar width and lesser alveolar height. Orthodontic treatment plan for retraction of anterior teeth must be based on these differences caused by variations in mandibular divergence. PMID:27437356

  3. Rare Presentation of Pulmonary Alveolar Proteinosis Causing Acute Respiratory Failure.

    PubMed

    Kroll, Ryan R; Kumar, Sameer; Grossman, Ronald F; Price, Charles; Srigley, John R

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by dysfunctional alveolar macrophages, which ineffectively clear surfactant and typically cause mild hypoxemia. Characteristic Computed Tomography findings are septal reticulations superimposed on ground-glass opacities in a crazy paving pattern, with a clear juxtaposition between affected and unaffected parenchyma. While traditionally PAP was diagnosed via biopsy, bronchoalveolar lavage (BAL) is usually sufficient; the fluid appears milky, and on microscopic examination there are foamy macrophages with eosinophilic granules and extracellular hyaline material that is Periodic Acid-Schiff positive. Standard therapy is whole lung lavage (WLL), although novel treatments are under development. The case presented is a 55-year-old woman with six months of progressive dyspnea, who developed hypoxemic respiratory failure requiring mechanical ventilation; she had typical findings of PAP on imaging and BAL. WLL was ultimately successful in restoring adequate oxygenation. Respiratory failure of this magnitude is a rare finding in PAP. PMID:27445536

  4. Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease.

    PubMed

    Whitsett, Jeffrey A; Wert, Susan E; Weaver, Timothy E

    2010-01-01

    The alveolar region of the lung creates an extensive epithelial surface that mediates the transfer of oxygen and carbon dioxide required for respiration after birth. Maintenance of pulmonary function depends on the function of type II epithelial cells that synthesize and secrete pulmonary surfactant lipids and proteins, reducing the collapsing forces created at the air-liquid interface in the alveoli. Genetic and acquired disorders associated with the surfactant system cause both acute and chronic lung disease. Mutations in the ABCA3, SFTPA, SFTPB, SFTPC, SCL34A2, and TERT genes disrupt type II cell function and/or surfactant homeostasis, causing neonatal respiratory failure and chronic interstitial lung disease. Defects in GM-CSF receptor function disrupt surfactant clearance, causing pulmonary alveolar proteinosis. Abnormalities in the surfactant system and disruption of type II cell homeostasis underlie the pathogenesis of pulmonary disorders previously considered idiopathic, providing the basis for improved diagnosis and therapies of these rare lung diseases. PMID:19824815

  5. Alveolar Surfactant Homeostasis and the Pathogenesis of Pulmonary Disease

    PubMed Central

    Whitsett, Jeffrey A.; Wert, Susan E.; Weaver, Timothy E.

    2014-01-01

    The alveolar region of the lung creates an extensive epithelial surface that mediates the transfer of oxygen and carbon dioxide required for respiration after birth. Maintenance of pulmonary function depends on the function of type II epithelial cells that synthesize and secrete pulmonary surfactant lipids and proteins, reducing the collapsing forces created at the air-liquid interface in the alveoli. Genetic and acquired disorders associated with the surfactant system cause both acute and chronic lung disease. Mutations in the ABCA3, SFTPA, SFTPB, SFTPC, SCL34A2, and TERT genes disrupt type II cell function and/or surfactant homeostasis, causing neonatal respiratory failure and chronic interstitial lung disease. Defects in GM-CSF receptor function disrupt surfactant clearance, causing pulmonary alveolar proteinosis. Abnormalities in the surfactant system and disruption of type II cell homeostasis underlie the pathogenesis of pulmonary disorders previously considered idiopathic, providing the basis for improved diagnosis and therapies of these rare lung diseases. PMID:19824815

  6. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    PubMed Central

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician. PMID:27471408

  7. Expression of β-Defensin Genes in Bovine Alveolar Macrophages

    PubMed Central

    Ryan, Lisa K.; Rhodes, Janice; Bhat, Meenakshi; Diamond, Gill

    1998-01-01

    Bovine alveolar macrophages (BAM) were examined for the expression of β-defensins and to determine whether their expression could be upregulated by bacterial lipopolysaccharide (LPS), as observed with β-defensins expressed in bovine tracheal epithelial cells. Four β-defensins were expressed constitutively in BAM, with bovine neutrophil β-defensin (BNBD)-4 and BNBD-5 being the most predominant. This is the first evidence of β-defensin gene expression in a mature myeloid cell. LPS had no effect on β-defensin expression in BAM, even though tumor necrosis factor alpha (TNF-α) production was induced. Nonbacterial inflammatory particles had little effect on β-defensin gene expression or TNF-α production in BAM. We hypothesize that constitutively expressed β-defensins of alveolar macrophages may have a role in lung host defense. PMID:9453661

  8. Solar Effects on Climate and the Maunder Minimum: Minimum Certainty

    NASA Technical Reports Server (NTRS)

    Rind, David

    2003-01-01

    The current state of our understanding of solar effects on climate is reviewed. As an example of the relevant issues, the climate during the Maunder Minimum is compared with current conditions in GCM simulations that include a full stratosphere and parameterized ozone response to solar spectral irradiance variability and trace gas changes. The GISS Global Climate/Middle Atmosphere Model coupled to a q-flux/mixed layer model is used for the simulations, which begin in 1500 and extend to the present. Experiments were made to investigate the effect of total versus spectrally-varying solar irradiance changes; spectrally-varying solar irradiance changes on the stratospheric ozone/climate response with both pre-industrial and present trace gases; and the impact on climate and stratospheric ozone of the preindustrial trace gases and aerosols by themselves. The results showed that: (1) the Maunder Minimum cooling relative to today was primarily associated with reduced anthropogenic radiative forcing, although the solar reduction added 40% to the overall cooling. There is no obvious distinguishing surface climate pattern between the two forcings. (2)The global and tropical response was greater than 1 C, in a model with a sensitivity of 1.2 C per W m-2. To reproduce recent low-end estimates would require a sensitivity 1/4 as large. (3) The global surface temperature change was similar when using the total and spectral irradiance prescriptions, although the tropical response was somewhat greater with the former, and the stratospheric response greater with the latter. (4) Most experiments produce a relative negative phase of the NAO/AO during the Maunder Minimum, with both solar and anthropogenic forcing equally capable, associated with the tropical cooling and relative poleward EP flux refraction. (5) A full stratosphere appeared to be necessary for the negative AO/NAO phase, as was the case with this model for global warming experiments, unless the cooling was very large

  9. 5 CFR 630.206 - Minimum charge.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Minimum charge. 630.206 Section 630.206... and General Provisions for Annual and Sick Leave § 630.206 Minimum charge. (a) Unless an agency establishes a minimum charge of less than one hour, or establishes a different minimum charge...

  10. 5 CFR 630.206 - Minimum charge.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Minimum charge. 630.206 Section 630.206... and General Provisions for Annual and Sick Leave § 630.206 Minimum charge. (a) Unless an agency establishes a minimum charge of less than one hour, or establishes a different minimum charge...

  11. Genetic Algorithms with Local Minimum Escaping Technique

    NASA Astrophysics Data System (ADS)

    Tamura, Hiroki; Sakata, Kenichiro; Tang, Zheng; Ishii, Masahiro

    In this paper, we propose a genetic algorithm(GA) with local minimum escaping technique. This proposed method uses the local minimum escaping techique. It can escape from the local minimum by correcting parameters when genetic algorithm falls into a local minimum. Simulations are performed to scheduling problem without buffer capacity using this proposed method, and its validity is shown.

  12. 5 CFR 551.301 - Minimum wage.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Minimum wage. 551.301 Section 551.301... FAIR LABOR STANDARDS ACT Minimum Wage Provisions Basic Provision § 551.301 Minimum wage. (a)(1) Except... employees wages at rates not less than the minimum wage specified in section 6(a)(1) of the Act for...

  13. 5 CFR 551.301 - Minimum wage.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Minimum wage. 551.301 Section 551.301... FAIR LABOR STANDARDS ACT Minimum Wage Provisions Basic Provision § 551.301 Minimum wage. (a)(1) Except... employees wages at rates not less than the minimum wage specified in section 6(a)(1) of the Act for...

  14. 5 CFR 551.301 - Minimum wage.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Minimum wage. 551.301 Section 551.301... FAIR LABOR STANDARDS ACT Minimum Wage Provisions Basic Provision § 551.301 Minimum wage. (a)(1) Except... employees wages at rates not less than the minimum wage specified in section 6(a)(1) of the Act for...

  15. 5 CFR 551.301 - Minimum wage.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Minimum wage. 551.301 Section 551.301... FAIR LABOR STANDARDS ACT Minimum Wage Provisions Basic Provision § 551.301 Minimum wage. (a)(1) Except... employees wages at rates not less than the minimum wage specified in section 6(a)(1) of the Act for...

  16. 5 CFR 551.301 - Minimum wage.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Minimum wage. 551.301 Section 551.301... FAIR LABOR STANDARDS ACT Minimum Wage Provisions Basic Provision § 551.301 Minimum wage. (a)(1) Except... employees wages at rates not less than the minimum wage specified in section 6(a)(1) of the Act for...

  17. Understanding the Minimum Wage: Issues and Answers.

    ERIC Educational Resources Information Center

    Employment Policies Inst. Foundation, Washington, DC.

    This booklet, which is designed to clarify facts regarding the minimum wage's impact on marketplace economics, contains a total of 31 questions and answers pertaining to the following topics: relationship between minimum wages and poverty; impacts of changes in the minimum wage on welfare reform; and possible effects of changes in the minimum wage…

  18. Secondary Alveolar Bone Grafting (CLEFTSiS) 2007-2010.

    PubMed

    Paterson, Michael; Rae, Jennifer; Paterson, Paul; Gilgrass, Toby; Devlin, Mark; McIntyre, Grant

    2016-03-01

    Objective To determine whether alveolar bone graft outcomes for unilateral and bilateral cleft lip and palate patients have continued to improve since the reorganization of cleft services in Scotland in 2000. Design Retrospective analysis of postoperative anterior occlusal radiographs. Patients and Participants Eighty-one of 106 patients who were eligible for alveolar bone grafting between 2007 and 2010 had suitable postoperative radiographs available. Interventions Twenty-seven percent of the patients (n = 22) had presurgical orthodontic intervention. All patients underwent alveolar bone grafting with bone harvested from the iliac crest. Main Outcome Measures The Kindelan bone-fill index was used to evaluate success. Weighted kappa statistics were used to assess intra- and interobserver reproducibility. A comparison was made with results from 2000 to 2004 to assess any improvement. Chi-square tests (or Fisher exact test) were used to determine whether outcomes differed depending on the laterality of the cleft, use of presurgical expansion, or age at bone grafting. Results Interobserver scoring agreement was good (weighted kappa = .383). Intraobserver reproducibility was greater (weighted kappas of .835 and .620). Success was achieved in 99% of bone grafts, compared with 76% in the period from 2000 to 2004 (P < .001). There was no statistically significant relationship between the laterality of the cleft (P = 1.000), use of presurgical expansion (P = 1.000), or age at time of bone grafting and outcome (P = .259). Conclusion Scottish secondary alveolar bone graft outcomes improved during 2007 to 2010 in comparison to the 2000 to 2004 results. PMID:26914161

  19. Endogenous lipoid pneumonia preceding diagnosis of pulmonary alveolar proteinosis.

    PubMed

    Antoon, James W; Hernandez, Michelle L; Roehrs, Phillip A; Noah, Terry L; Leigh, Margaret W; Byerley, Julie S

    2016-03-01

    Pulmonary alveolar proteinosis (PAP) is an under-reported and under-diagnosed condition, with a high percentage of cases found on autopsy or late stage disease. The etiology of PAP includes genetic, primary (anti-granulocyte-macrophage colony-stimulating factor antibodies) and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes. Here, we present the first reported pediatric case of endogenous lipoid pneumonia and non-specific interstitial pneumonitis preceding the development of PAP. PMID:25103284

  20. Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions.

    PubMed

    Intini, G; Katsuragi, Y; Kirkwood, K L; Yang, S

    2014-05-01

    This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of

  1. Alveolar cell carcinoma: diagnostic pitfalls in evaluating the chest roentgenogram

    SciTech Connect

    Shin, M.S.; Bailey, W.C.

    1985-02-01

    A report is given of two patients with initial symptoms of congestive heart failure who had an extensive work-up that failed to reveal any signs of pulmonary malignancy. Subsequent biopsy by fiberoptic bronchoscopy confirmed alveolar cell carcinoma in both cases, suggesting that bronchoscopy with biopsy should be considered in patients with congestive heart failure if pulmonary edema does not resolve with appropriate therapy. 11 references, 2 figures.

  2. Respiratory gas exchange using a triaxial alveolar gas diagram.

    PubMed Central

    Fuster, J. F.; Pages, T.; Palacios, L.

    1993-01-01

    A triaxial alveolar gas diagram to depict fractional concentration of oxygen, carbon dioxide and nitrogen is described, in which the R = 1 line is always implicit. Although it is not claimed that this representation leads to new insights into respiratory physiology, a method of plotting on a triaxial coordinate system has been found to be well suited to many applications when a direct display of fractional nitrogen concentration is required. PMID:8303637

  3. Hyperoxia induces alveolar epithelial-to-mesenchymal cell transition

    PubMed Central

    Wang, Wenyi; Kato, Satomi; Colvocoresses-Dodds, Jennifer; Fifadara, Nimita H.; Gauthier, Theresa W.; Helms, My N.; Carlton, David P.; Brown, Lou Ann S.

    2013-01-01

    Myofibroblast accumulation is a pathological feature of lung diseases requiring oxygen therapy. One possible source for myofibroblasts is through the epithelial-to-mesenchymal transition (EMT) of alveolar epithelial cells (AEC). To study the effects of oxygen on alveolar EMT, we used RLE-6TN and ex vivo lung slices and found that hyperoxia (85% O2, H85) decreased epithelial proteins, presurfactant protein B (pre-SpB), pro-SpC, and lamellar protein by 50% and increased myofibroblast proteins, α-smooth muscle actin (α-SMA), and vimentin by over 200% (P < 0.05). In AEC freshly isolated from H85-treated rats, mRNA for pre-SpB and pro-SpC was diminished by ∼50% and α-SMA was increased by 100% (P < 0.05). Additionally, H85 increased H2O2 content, and H2O2 (25–50 μM) activated endogenous transforming growth factor-β1 (TGF-β1), as evident by H2DCFDA immunofluorescence and ELISA (P < 0.05). Both hyperoxia and H2O2 increased SMAD3 phosphorylation (260% of control, P < 0.05). Treating cultured cells with TGF-β1 inhibitors did not prevent H85-induced H2O2 production but did prevent H85-mediated α-SMA increases and E-cadherin downregulation. Finally, to determine the role of TGF-β1 in hyperoxia-induced EMT in vivo, we evaluated AEC from H85-treated rats and found that vimentin increased ∼10-fold (P < 0.05) and that this effect was prevented by intraperitoneal TGF-β1 inhibitor SB-431542. Additionally, SB-431542 treatment attenuated changes in alveolar histology caused by hyperoxia. Our studies indicate that hyperoxia promotes alveolar EMT through a mechanism that is dependent on activation of TGF-β1 signaling. PMID:24375795

  4. Hyperoxia induces alveolar epithelial-to-mesenchymal cell transition.

    PubMed

    Vyas-Read, Shilpa; Wang, Wenyi; Kato, Satomi; Colvocoresses-Dodds, Jennifer; Fifadara, Nimita H; Gauthier, Theresa W; Helms, My N; Carlton, David P; Brown, Lou Ann S

    2014-02-15

    Myofibroblast accumulation is a pathological feature of lung diseases requiring oxygen therapy. One possible source for myofibroblasts is through the epithelial-to-mesenchymal transition (EMT) of alveolar epithelial cells (AEC). To study the effects of oxygen on alveolar EMT, we used RLE-6TN and ex vivo lung slices and found that hyperoxia (85% O2, H85) decreased epithelial proteins, presurfactant protein B (pre-SpB), pro-SpC, and lamellar protein by 50% and increased myofibroblast proteins, α-smooth muscle actin (α-SMA), and vimentin by over 200% (P < 0.05). In AEC freshly isolated from H85-treated rats, mRNA for pre-SpB and pro-SpC was diminished by ∼50% and α-SMA was increased by 100% (P < 0.05). Additionally, H85 increased H2O2 content, and H2O2 (25-50 μM) activated endogenous transforming growth factor-β1 (TGF-β1), as evident by H2DCFDA immunofluorescence and ELISA (P < 0.05). Both hyperoxia and H2O2 increased SMAD3 phosphorylation (260% of control, P < 0.05). Treating cultured cells with TGF-β1 inhibitors did not prevent H85-induced H2O2 production but did prevent H85-mediated α-SMA increases and E-cadherin downregulation. Finally, to determine the role of TGF-β1 in hyperoxia-induced EMT in vivo, we evaluated AEC from H85-treated rats and found that vimentin increased ∼10-fold (P < 0.05) and that this effect was prevented by intraperitoneal TGF-β1 inhibitor SB-431542. Additionally, SB-431542 treatment attenuated changes in alveolar histology caused by hyperoxia. Our studies indicate that hyperoxia promotes alveolar EMT through a mechanism that is dependent on activation of TGF-β1 signaling. PMID:24375795

  5. SOCS-3 Regulates Alveolar Bone Loss in Experimental Periodontitis.

    PubMed

    Papathanasiou, E; Kantarci, A; Konstantinidis, A; Gao, H; Van Dyke, T E

    2016-08-01

    The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in restraining periodontal inflammation. We hypothesized that SOCS-3 regulates alveolar bone loss in experimental periodontitis. Periodontal bone loss was induced in 16-wk-old myeloid-specific SOCS-3-knockout and wild-type (WT) C57Bl6-B.129 mice by oral inoculation 9 times with 10(9) colony-forming units of Porphyromonas gingivalis A7436 through an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 wk after the last oral inoculation. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3-knockout mice as compared with P. gingivalis-infected WT mice by direct morphologic measurements, micro-computed tomography analyses, and quantitative histology. Loss of SOCS-3 function resulted in an increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promotes a higher P. gingivalis lipopolysaccharide-induced inflammatory response with higher secretion of IL-1β, IL-6, and KC (IL-8) by peritoneal macrophages as compared with WT controls. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in periodontitis. PMID:27126447

  6. Sensitization of the transient receptor potential vanilloid type 1 ion channel by isoflurane or sevoflurane does not result in extracellular signal-regulated kinase 1/2 activation in rat spinal dorsal horn neurons.

    PubMed

    White, J P M; Cibelli, M; Fidalgo, A R; Paule, C C; Anderson, P J; Jenes, A; Rice, A S C; Nagy, I

    2010-03-17

    Clinically relevant concentrations of isoflurane or sevoflurane sensitize transient receptor potential vanilloid type 1 to several of its activators, including capsaicin. It has, moreover, been suggested these volatile general anaesthetics may augment nociceptive signalling arising from surgical procedures and thereby contribute to post-operative pain. To investigate this suggestion, we have studied intraplantar capsaicin injection-induced phosphorylation of extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons (which is a recognized marker of spinal nociceptive processing) in rat during isoflurane or sevoflurane anaesthesia after 60 min under anaesthesia. Control animals were anaesthetized with pentobarbital (which of itself does not activate extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons). Unilateral intraplantar capsaicin injection in control animals evoked extracellular signal-regulated kinase 1/2 phosphorylation in a group of neurons in lamina I and lamina II of the ipsilateral spinal dorsal horn in a somatotopically appropriate area. In contrast, both anaesthetic gases (given for 60 min and without subsequent capsaicin injection) induced extracellular signal-regulated kinase 1/2 activation in a different group of mainly lamina I neurons bilaterally. The total number of spinal dorsal horn neurons labelled on the ipliateral side following capsaicin injection into the isoflurane-, or sevoflurane-, anaesthetized animals was significantly less than that produced by capsaicin alone. Further, capsaicin injection into isoflurane-, or sevoflurane-, anaesthetized animals reduced extracellular signal-regulated kinase 1/2 phosphorylation induced by the gases alone on both sides. These findings do not support the suggestion that isoflurane-, or sevoflurane-, induced sensitization of transient receptor potential vanilloid type 1 by capsaicin, or other agonist, is translated into induction of spinal nociceptive processing and

  7. Neuroprotective effect of ginsenoside Rg1 prevents cognitive impairment induced by isoflurane anesthesia in aged rats via antioxidant, anti-inflammatory and anti-apoptotic effects mediated by the PI3K/AKT/GSK-3β pathway.

    PubMed

    Zhang, Yini; Zhang, Zhao; Wang, Haitang; Cai, Nan; Zhou, Shuang; Zhao, Yaoping; Chen, Xue; Zheng, Shaoqiang; Si, Qi; Zhang, Wei

    2016-09-01

    Ginsenoside Rg1 is the primary active substance in ginseng, and it has multiple pharmacological actions. Investigations on the pharmacologic action of ginsenoside Rg1 have developed, with a particular focus on the regulation of metabolism. The present study hypothesized that the neuroprotective effects of ginsenoside Rg1 prevent cognitive impairment induced by isoflurane anesthesia via antioxidant, anti‑inflammatory and anti‑apoptotic effects, mediated by the phosphoinositide 3‑kinase (PI3K)/AKT/glycogen synthase kinase‑3β (GSK‑3β) pathway in aged rats. Sprague‑Dawley rats were divided into isoflurane and ginsenoside Rg1 groups and were treated with 20 mg/kg ginsenoside Rg1 for 7 days. Morris water maze was performed to analyze the cognitive function of the rats. Enzyme‑linked immunosorbent assays were used to analyze the levels of malondialdehyde, glutathione, interleukin (IL)‑1β, IL‑6 and caspase 3. The protein expression levels of AKT, GSK 3β, p21WAF1/CIP1 and p53 were measured using western blot analysis. Ginsenoside Rg1 significantly improved cognitive function, and exhibited antioxidant and anti‑inflammatory effects, demonstrating the neuroprotective effects of ginsenoside Rg1 against the effect of isoflurane anesthesia in the rats. In addition, ginsenoside Rg1 significantly reduced caspase‑3 activity, upregulated the expression of PI3K/AKT/GSK‑3β and downregulated the mRNA expression levels of p21WAF1/CIP1 and p53 in the aged rats exposed to isoflurane anesthesia. The data obtained in the present study provided evidence that the neuroprotective effects of ginsenoside Rg1 prevented the cognitive impairment induced by isoflurane anesthesia via antioxidant, anti‑inflammatory and anti‑apoptotic effects, mediated by the PI3K/AKT/GSK‑3β pathway. PMID:27485139

  8. Alveolar epithelial type II cell: defender of the alveolus revisited

    PubMed Central

    Fehrenbach, Heinz

    2001-01-01

    In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2) cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, and host defence. AE2 cells proliferate, differentiate into AE1 cells, and remove apoptotic AE2 cells by phagocytosis, thus contributing to epithelial repair. AE2 cells may act as immunoregulatory cells. AE2 cells interact with resident and mobile cells, either directly by membrane contact or indirectly via cytokines/growth factors and their receptors, thus representing an integrative unit within the alveolus. Although most data support the concept, the controversy about the character of hyperplastic AE2 cells, reported to synthesise profibrotic factors, proscribes drawing a definite conclusion today. PMID:11686863

  9. Three Dimensional Alveolar Flow Phenomena Using a CFD Approach

    NASA Astrophysics Data System (ADS)

    Sznitman, Josue

    2005-11-01

    Respiratory flows in the lung periphery are characterized by low Reynolds numbers (typically Re<1) in sub-millimeter airways marked by the presence of alveoli (gas exchange units). We present for realistic breathing conditions using CFD simulations (CFX-5.7.1), 3D velocity fields and flow patterns induced by the expansion/contraction of alveoli and acinar ducts during oscillatory flow. Based on anatomical data, the alveolus and airway are modeled as a spherical cap connected to a cylindrical duct, both subject to moving wall boundary conditions simulating respiration. The resulting 3D flow patterns are complex and governed by the ratio of the alveolar to ductal flow rates. This ratio describes the interplay between alveolar recirculation, induced by the ductal shear flow over the alveolus opening, and alveolar radial flow, induced by the expansion/contraction motion. Our 3D results are in good agreement with 2D simulations reported in the literature. Although convection mechanisms may transport gas along acinar ducts and deeper into the acinus, velocity fields within alveoli predict that upon gas entering them, transport is then solely dominated by diffusion mechanisms.

  10. Requirement of alveolar bone formation for eruption of rat molars.

    PubMed

    Wise, Gary E; He, Hongzhi; Gutierrez, Dina L; Ring, Sherry; Yao, Shaomian

    2011-10-01

    Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (Bmp6), was inhibited by injection of the first mandibular molar of the rat with a small interfering RNA (siRNA) targeted against Bmp6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption was either delayed or completely inhibited (seven molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced compared with the erupted first-molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that Bmp6 may be essential for promoting this growth. PMID:21896048

  11. Requirement of alveolar bone formation for eruption of rat molars

    PubMed Central

    Wise, Gary E.; He, Hongzhi; Gutierrez, Dina L.; Ring, Sherry; Yao, Shaomian

    2011-01-01

    Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (BMP6), was inhibited by injection of the 1st mandibular molar of the rat with an siRNA targeted against BMP6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption either was delayed or completely inhibited (7 molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced as compared to the erupted first molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that BMP6 may be an essential gene for promoting this growth. PMID:21896048

  12. Cigarette smoke extract affects mitochondrial function in alveolar epithelial cells.

    PubMed

    Ballweg, Korbinian; Mutze, Kathrin; Königshoff, Melanie; Eickelberg, Oliver; Meiners, Silke

    2014-12-01

    Cigarette smoke is the main risk factor for chronic obstructive pulmonary disease (COPD). Exposure of cells to cigarette smoke induces an initial adaptive cellular stress response involving increased oxidative stress and induction of inflammatory signaling pathways. Exposure of mitochondria to cellular stress alters their fusion/fission dynamics. Whereas mild stress induces a prosurvival response termed stress-induced mitochondrial hyperfusion, severe stress results in mitochondrial fragmentation and mitophagy. In the present study, we analyzed the mitochondrial response to mild and nontoxic doses of cigarette smoke extract (CSE) in alveolar epithelial cells. We characterized mitochondrial morphology, expression of mitochondrial fusion and fission genes, markers of mitochondrial proteostasis, as well as mitochondrial functions such as membrane potential and oxygen consumption. Murine lung epithelial (MLE)12 and primary mouse alveolar epithelial cells revealed pronounced mitochondrial hyperfusion upon treatment with CSE, accompanied by increased expression of the mitochondrial fusion protein mitofusin 2 and increased metabolic activity. We did not observe any alterations in mitochondrial proteostasis, i.e., induction of the mitochondrial unfolded protein response or mitophagy. Therefore, our data indicate an adaptive prosurvival response of mitochondria of alveolar epithelial cells to nontoxic concentrations of CSE. A hyperfused mitochondrial network, however, renders the cell more vulnerable to additional stress, such as sustained cigarette smoke exposure. As such, cigarette smoke-induced mitochondrial hyperfusion, although part of a beneficial adaptive stress response in the first place, may contribute to the pathogenesis of COPD. PMID:25326581

  13. CHARACTERIZATION OF ALVEOLAR EPITHELIAL CELLS CULTURED IN SEMIPERMEABLE HOLLOW FIBERS

    PubMed Central

    Grek, Christina L.; Newton, Danforth A.; Qiu, Yonhzhi; Wen, Xuejun; Spyropoulos, Demetri D.; Baatz, John E.

    2012-01-01

    Cell culture methods commonly used to represent alveolar epithelial cells in vivo have lacked airflow, a 3-dimensional air-liquid interface, and dynamic stretching characteristics of native lung tissue—physiological parameters critical for normal phenotypic gene expression and cellular function. Here the authors report the development of a selectively semipermeable hollow fiber culture system that more accurately mimics the in vivo microenvironment experienced by mammalian distal airway cells than in conventional or standard air-liquid interface culture. Murine lung epithelial cells (MLE-15) were cultured within semipermeable polyurethane hollow fibers and introduced to controlled airflow through the microfiber interior. Under these conditions, MLE-15 cells formed confluent monolayers, demonstrated a cuboidal morphology, formed tight junctions, and produced and secreted surfactant proteins. Numerous lamellar bodies and microvilli were present in MLE-15 cells grown in hollow fiber culture. Conversely, these alveolar type II cell characteristics were reduced in MLE-15 cells cultured in conventional 2D static culture systems. These data support the hypothesis that MLE-15 cells grown within our microfiber culture system in the presence of airflow maintain the phenotypic characteristics of type II cells to a higher degree than those grown in standard in vitro cell culture models. Application of our novel model system may prove advantageous for future studies of specific gene and protein expression involving alveolar epithelial or bronchiolar epithelial cells. PMID:19263283

  14. Characterization of stem cells from alveolar periodontal ligament.

    PubMed

    Wang, Lei; Shen, Huan; Zheng, Wei; Tang, Liang; Yang, Zhenhua; Gao, Yuan; Yang, Qingtian; Wang, Chen; Duan, Yinzhong; Jin, Yan

    2011-04-01

    Complete and predicable regeneration of complex periodontal structures, which include cementum, periodontal ligament (PDL), and alveolar bone, has been a great challenge for periodontal researchers. It is generally believed that human PDL from the root surface contains stem cells (r-PDLSCs), which can enhance cementum/PDL-like tissues regeneration in vivo. In this work, PDL was found to possess asymmetrically distributed stem cells observed by long-term bromodeoxyuridine (BrdU) labeling. Putative stem cells from human PDL on the alveolar bone surface (a-PDLSCs) were then isolated and characterized. It was shown that a-PDLSCs exhibited strong proliferation capability and expressed high percentages of mesenchymal stem cell markers. Comparatively, a-PDLSCs had higher multilineage differentiation potential than r-PDLSCs with regard to both osteogenic and adipogenic differentiation. Alkaline phosphatase activity and the expression of mineralization-related markers of a-PDLSCs were also higher than those of r-PDLSCs. In vivo, a-PDLSCs could regenerate bone/PDL-like structures and repair critical-size defects created in calvarial bone of NOD/SCID mice. Autologous PDLSC-mediated periodontal regeneration showed that a-PDLSCs could accomplish reconstruction of alveolar bone more perfectly than r-PDLSCs. Our data suggest that PDLSCs may have quite different characteristics depending on locations. a-PDLSCs may take a synergistic effect with r-PDLSCs in periodontal regeneration. PMID:21186958

  15. Pulmonary surfactant: no mere paint on the alveolar wall.

    PubMed

    Nicholas, T E

    1996-12-01

    The gas-liquid interface within the alveolus is completely lined with a complex mixture of lipids and unique proteins termed pulmonary surfactant, which both reduces surface tension and permits it to vary directly with the radius of curvature. In this way it minimizes the work of breathing and permits alveoli of different sizes to exist in equilibrium. However, surfactant does far more in that it also controls fluid balance in the lung and appears to play a key role in host defence. Either a deficiency in surfactant or an aberrant surfactant results in atelectasis and oedema. The surfactant system is very dynamic: alveolar surfactant phosphatidylcholine, the principal component, having a half life of only a few hours, with as much as 85% being recycled. Although distortion of the alveolar type II cell is now accepted as the principal stimulus for release, much remains to be discovered of modulating factors and intracellular signalling in the control of surfactant homeostasis. Likewise, many questions remain concerning the control of synthesis of the surfactant phospholipids, neutral lipids and proteins and their assembly into the tubular myelin form of alveolar surfactant, the refining of the monolayer with breathing, the control of re-uptake of different components into the type II cells and the roles of the proteins. PMID:9441113

  16. Evaluation of optical reflectance techniques for imaging of alveolar structure

    NASA Astrophysics Data System (ADS)

    Unglert, Carolin I.; Namati, Eman; Warger, William C.; Liu, Linbo; Yoo, Hongki; Kang, DongKyun; Bouma, Brett E.; Tearney, Guillermo J.

    2012-07-01

    Three-dimensional (3-D) visualization of the fine structures within the lung parenchyma could advance our understanding of alveolar physiology and pathophysiology. Current knowledge has been primarily based on histology, but it is a destructive two-dimensional (2-D) technique that is limited by tissue processing artifacts. Micro-CT provides high-resolution three-dimensional (3-D) imaging within a limited sample size, but is not applicable to intact lungs from larger animals or humans. Optical reflectance techniques offer the promise to visualize alveolar regions of the large animal or human lung with sub-cellular resolution in three dimensions. Here, we present the capabilities of three optical reflectance techniques, namely optical frequency domain imaging, spectrally encoded confocal microscopy, and full field optical coherence microscopy, to visualize both gross architecture as well as cellular detail in fixed, phosphate buffered saline-immersed rat lung tissue. Images from all techniques were correlated to each other and then to corresponding histology. Spatial and temporal resolution, imaging depth, and suitability for in vivo probe development were compared to highlight the merits and limitations of each technology for studying respiratory physiology at the alveolar level.

  17. Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide.

    PubMed

    Castellana, Giuseppe; Castellana, Giorgio; Gentile, Mattia; Castellana, Roberto; Resta, Onofrio

    2015-12-01

    Pulmonary alveolar microlithiasis (PAM) is a rare disease characterised by the widespread intra-alveolar accumulation of minute calculi called microliths. It is caused by mutation of the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells. The present study explores the epidemiological, familial, genetic, clinical, diagnostic, radiological and therapeutic aspects with the aim of contributing to a better understanding of this uncommon disease.We searched articles on PAM published up to December 2014 and 544 papers were found, accounting for 1022 cases.PAM is present in all continents and in many nations, in particular in Turkey, China, Japan, India, Italy and the USA. Familiality is frequent. The clinical course is not uniform and the causes of this clinical variability seem to be largely nongenetic. The optimal diagnostic procedure is the association of chest high-resolution computed tomography (HRCT) with bronchoalveolar lavage, but a chest radiograph may suffice in families in which a case has already been diagnosed. Moreover, chest radiography and HRCT allow the classification of the evolutionary phase of the disease and its severity. At present lung transplantation is the only effective therapy. However, better knowledge of the gene responsible offers hope for new therapies. PMID:26621975

  18. Chronic alcohol ingestion changes the landscape of the alveolar epithelium.

    PubMed

    Downs, Charles A; Trac, David; Brewer, Elizabeth M; Brown, Lou Ann; Helms, My N

    2013-01-01

    Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH) on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC). The cascading effect of tissue and phagocytic Nadph oxidase (Nox) may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM) function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS) for which hospitalized alcoholics are at an increased risk. PMID:23509726

  19. Quality assessment of systematic reviews on alveolar socket preservation.

    PubMed

    Moraschini, V; Barboza, E Dos S P

    2016-09-01

    The aim of this overview was to evaluate and compare the quality of systematic reviews, with or without meta-analysis, that have evaluated studies on techniques or biomaterials used for the preservation of alveolar sockets post tooth extraction in humans. An electronic search was conducted without date restrictions using the Medline/PubMed, Cochrane Library, and Web of Science databases up to April 2015. Eligibility criteria included systematic reviews, with or without meta-analysis, focused on the preservation of post-extraction alveolar sockets in humans. Two independent authors assessed the quality of the included reviews using AMSTAR and the checklist proposed by Glenny et al. in 2003. After the selection process, 12 systematic reviews were included. None of these reviews obtained the maximum score using the quality assessment tools implemented, and the results of the analyses were highly variable. A significant statistical correlation was observed between the scores of the two checklists. A wide structural and methodological variability was observed between the systematic reviews published on the preservation of alveolar sockets post tooth extraction. None of the reviews evaluated obtained the maximum score using the two quality assessment tools implemented. PMID:27061478

  20. GMTI radar minimum detectable velocity.

    SciTech Connect

    Richards, John Alfred

    2011-04-01

    Minimum detectable velocity (MDV) is a fundamental consideration for the design, implementation, and exploitation of ground moving-target indication (GMTI) radar imaging modes. All single-phase-center air-to-ground radars are characterized by an MDV, or a minimum radial velocity below which motion of a discrete nonstationary target is indistinguishable from the relative motion between the platform and the ground. Targets with radial velocities less than MDV are typically overwhelmed by endoclutter ground returns, and are thus not generally detectable. Targets with radial velocities greater than MDV typically produce distinct returns falling outside of the endoclutter ground returns, and are thus generally discernible using straightforward detection algorithms. This document provides a straightforward derivation of MDV for an air-to-ground single-phase-center GMTI radar operating in an arbitrary geometry.

  1. Proinflammatory response of alveolar epithelial cells is enhanced by alveolar macrophage-produced TNF-alpha during pulmonary ischemia-reperfusion injury.

    PubMed

    Sharma, Ashish K; Fernandez, Lucas G; Awad, Alaa S; Kron, Irving L; Laubach, Victor E

    2007-07-01

    Pulmonary ischemia-reperfusion (IR) injury entails acute activation of alveolar macrophages followed by neutrophil sequestration. Although proinflammatory cytokines and chemokines such as TNF-alpha and monocyte chemoattractant protein-1 (MCP-1) from macrophages are known to modulate acute IR injury, the contribution of alveolar epithelial cells to IR injury and their intercellular interactions with other cell types such as alveolar macrophages and neutrophils remain unclear. In this study, we tested the hypothesis that following IR, alveolar macrophage-produced TNF-alpha further induces alveolar epithelial cells to produce key chemokines that could then contribute to subsequent lung injury through the recruitment of neutrophils. Cultured RAW264.7 macrophages and MLE-12 alveolar epithelial cells were subjected to acute hypoxia-reoxygenation (H/R) as an in vitro model of pulmonary IR. H/R (3 h/1 h) significantly induced KC, MCP-1, macrophage inflammatory protein-2 (MIP-2), RANTES, and IL-6 (but not TNF-alpha) by MLE-12 cells, whereas H/R induced TNF-alpha, MCP-1, RANTES, MIP-1alpha, and MIP-2 (but not KC) by RAW264.7 cells. These results were confirmed using primary murine alveolar macrophages and primary alveolar type II cells. Importantly, using macrophage and epithelial coculture methods, the specific production of TNF-alpha by H/R-exposed RAW264.7 cells significantly induced proinflammatory cytokine/chemokine expression (KC, MCP-1, MIP-2, RANTES, and IL-6) by MLE-12 cells. Collectively, these results demonstrate that alveolar type II cells, in conjunction with alveolar macrophage-produced TNF-alpha, contribute to the initiation of acute pulmonary IR injury via a proinflammatory cascade. The release of key chemokines, such as KC and MIP-2, by activated type II cells may thus significantly contribute to neutrophil sequestration during IR injury. PMID:17416740

  2. Electrical nerve stimulation method for intraoperative localization of the inferior alveolar nerve within the mandible: a pilot study in rabbits.

    PubMed

    Kuyumcu, F; Erdogan, Ö; Güçlü, B

    2015-11-01

    The efficacy of the electrical nerve stimulation method for localizing the inferior alveolar nerve (IAN) within the mandibular bone was evaluated. Six New Zealand rabbits were used (both sides of the mandible). The IAN was stimulated through the mandibular bone and compound action potentials (CAPs) were recorded proximally from the main trunk of the nerve. Stimulation current pulse widths were set at 0.05, 0.1, 0.3, 0.5, and 1ms. The minimum current magnitude that generated a CAP with a criterion level (300mV peak-to-peak amplitude) was measured in the range of 0.05-5mA. Correlations between the distance of the IAN from the active electrode site and the minimum current magnitudes were studied for each pulse width. The correlation coefficients were 0.678, 0.807, 0.893, 0.851, and 0.890 for the pulse widths of 0.05, 0.1, 0.3, 0.5, and 1ms, respectively. The minimum current producing the criterion CAP response in the IAN was significantly (P<0.0001 for all pulse widths) and highly correlated with the distance between the stimulation site and the nerve. The results suggest that electrical nerve stimulation is a promising method that can be used for the localization of the IAN, especially during mandibular implant surgery. PMID:26116064

  3. Elemental analysis of lung tissue particles and intracellular iron content of alveolar macrophages in pulmonary alveolar proteinosis

    PubMed Central

    2011-01-01

    Background Pulmonary alveolar proteinosis (PAP) is a rare disease occurred by idiopathic (autoimmune) or secondary to particle inhalation. The in-air microparticle induced X-ray emission (in-air micro-PIXE) system performs elemental analysis of materials by irradiation with a proton microbeam, and allows visualization of the spatial distribution and quantitation of various elements with very low background noise. The aim of this study was to assess the secondary PAP due to inhalation of harmful particles by employing in-air micro-PIXE analysis for particles and intracellular iron in parafin-embedded lung tissue specimens obtained from a PAP patient comparing with normal lung tissue from a non-PAP patient. The iron inside alveolar macrophages was stained with Berlin blue, and its distribution was compared with that on micro-PIXE images. Results The elements composing particles and their locations in the PAP specimens could be identified by in-air micro-PIXE analysis, with magnesium (Mg), aluminum (Al), silicon (Si), phosphorus (P), sulfur (S), scandium (Sc), potassium (K), calcium (Ca), titanium (Ti), chromium (Cr), copper (Cu), manganase (Mn), iron (Fe), and zinc (Zn) being detected. Si was the major component of the particles. Serial sections stained by Berlin blue revealed accumulation of sideromacrophages that had phagocytosed the particles. The intracellular iron content of alveolar macrophage from the surfactant-rich area in PAP was higher than normal lung tissue in control lung by both in-air micro-PIXE analysis and Berlin blue staining. Conclusion The present study demonstrated the efficacy of in-air micro-PIXE for analyzing the distribution and composition of lung particles. The intracellular iron content of single cells was determined by simultaneous two-dimensional and elemental analysis of paraffin-embedded lung tissue sections. The results suggest that secondary PAP is associated with exposure to inhaled particles and accumulation of iron in alveolar

  4. Broadband Local Field Potentials Correlate with Spontaneous Fluctuations in Functional Magnetic Resonance Imaging Signals in the Rat Somatosensory Cortex Under Isoflurane Anesthesia

    PubMed Central

    Pan, Wen-Ju; Thompson, Garth; Magnuson, Matthew; Majeed, Waqas; Jaeger, Dieter

    2011-01-01

    Abstract Resting-state functional magnetic resonance imaging (fMRI) is widely used for exploring spontaneous brain activity and large-scale networks; however, the neural processes underlying the observed resting-state fMRI signals are not fully understood. To investigate the neural correlates of spontaneous low-frequency fMRI fluctuations and functional connectivity, we developed a rat model of simultaneous fMRI and multiple-site intracortical neural recordings. This allowed a direct comparison to be made between the spontaneous signals and interhemispheric connectivity measured with the two modalities. Results show that low-frequency blood oxygen level-dependent (BOLD) fluctuations (<0.1 Hz) correlate significantly with slow power modulations (<0.1 Hz) of local field potentials (LFPs) in a broad frequency range (1–100 Hz) under isoflurane anesthesia (1%–1.8%). Peak correlation occurred between neural and hemodynamic activity when the BOLD signal was delayed by ∼4 sec relative to the LFP signal. The spatial location and extent of correlation was highly reproducible across studies, with the maximum correlation localized to a small area surrounding the site of microelectrode recording and to the homologous area in the contralateral hemisphere for most rats. Interhemispheric connectivity was calculated using BOLD correlation and band-limited LFP (1–4, 4–8, 8–14, 14–25, 25–40, and 40–100 Hz) coherence. Significant coherence was observed for the slow power changes of all LFP frequency bands as well as in the low-frequency BOLD data. A preliminary investigation of the effect of anesthesia on interhemispheric connectivity indicates that coherence in the high-frequency LFP bands declines with increasing doses of isoflurane, whereas coherence in the low-frequency LFP bands and the BOLD signal increases. These findings suggest that resting-state fMRI signals might be a reflection of broadband LFP power modulation, at least in isoflurane

  5. Therapeutic Whole-Lung Lavage for Pulmonary Alveolar Proteinosis: A Procedural Update.

    PubMed

    Abdelmalak, Basem B; Khanna, Ashish K; Culver, Daniel A; Popovich, Marc J

    2015-07-01

    Pulmonary alveolar proteinosis is a disease caused by increased accumulation and impaired clearance of surfactant by alveolar macrophages. This narrative review summarizes the role of therapeutic whole-lung lavage in the management of pulmonary alveolar proteinosis. We describe the preprocedural evaluation, indications, and anesthetic considerations, along with step-by step technical aspects of the procedure, postoperative recovery, potential complications, and long-term outcomes. PMID:26165897

  6. Isolation and Culture of Alveolar Epithelial Type I and Type II Cells from Rat Lungs

    PubMed Central

    Gonzalez, Robert F.; Dobbs, Leland G.

    2014-01-01

    The pulmonary alveolar epithelium, comprised of alveolar Type I (TI) and Type II (TII) cells, covers more than 99% of the internal surface area of the lungs. The study of isolated and cultured alveolar epithelial TI and TII cells has provided a large amount of information about the functions of both cell types. This chapter provides information about methods for isolating and culturing both of these cell types from rat lungs. PMID:23097106

  7. A Case of Alveolar Echinococcosis Presenting as Cerebral and Spinal Intradural Metastases.

    PubMed

    Atalan, Guneri; Sivrioglu, Ali Kemal; Sönmez, Güner; Celik, Mahir; Simsek, Berksan

    2016-06-01

    Alveolar echinococcosis is a chronic and serious, even lethal, parasitic infection caused by the helminth Echinococcus multilocularis. The involvement of Central Nervous System is reported to be 1-3% in literature. Brain involvement is considered a sign of the terminal phase of alveolar echinococcosis. We here in reported a 67-year-old female who had liver alveolar hydatid disease with brain and spinal intradural metastases. PMID:27551181

  8. A Case of Alveolar Echinococcosis Presenting as Cerebral and Spinal Intradural Metastases

    PubMed Central

    Atalan, Guneri; Sivrioglu, Ali Kemal; Sönmez, Güner; Celik, Mahir; Simsek, Berksan

    2016-01-01

    Alveolar echinococcosis is a chronic and serious, even lethal, parasitic infection caused by the helminth Echinococcus multilocularis. The involvement of Central Nervous System is reported to be 1–3% in literature. Brain involvement is considered a sign of the terminal phase of alveolar echinococcosis. We here in reported a 67-year-old female who had liver alveolar hydatid disease with brain and spinal intradural metastases. PMID:27551181

  9. Alveolar recruitment in patients in the immediate postoperative period of cardiac surgery.

    PubMed

    Padovani, Cauê; Cavenaghi, Odete Mauad

    2011-01-01

    Lung complications during postoperative period of cardiac surgery are frequently, highlighting atelectasis and hypoxemia. Alveolar recruitment maneuvers have an important role in the prevention and treatment of these complications. Thus, this study reviewed and updated the alveolar recruitment maneuvers performance in the immediate postoperative period of cardiac surgery. We noted the efficacy of alveolar recruitment through different specific techniques and the need for development of new studies. PMID:21881720

  10. Zinc Insufficiency Mediates Ethanol-Induced Alveolar Macrophage Dysfunction in the Pregnant Female Mouse

    PubMed Central

    Konomi, Juna V.; Harris, Frank L.; Ping, Xiao-Du; Gauthier, Theresa W.; Brown, Lou Ann S.

    2015-01-01

    Aims: (a) Establish the minimum number of weeks of chronic ethanol ingestion needed to perturb zinc homeostasis, (b) Examine intracellular zinc status in the alveolar macrophages (AMs) when ethanol ingestion is combined with pregnancy, (c) Investigate whether in vitro zinc treatment reverses the effects of ethanol ingestion on the AM. Methods: C57BL/6 female mice were fed a liquid diet (±25% ethanol-derived calories) during preconception and pregnancy. The control group was pair-fed to the ethanol group. In the isolated AMs, we measured intracellular AM zinc levels, zinc transporter expression, alternative activation and phagocytic index. Zinc acetate was added to some cells prior to analysis. Results: Intracellular zinc levels in the AM decreased within 3 weeks of ethanol ingestion. After ethanol ingestion prior to and during pregnancy, zinc transporter expression and intracellular zinc levels were decreased in the AMs when compared with controls. Bacterial clearance was decreased because the AMs were alternatively activated. In vitro additions of zinc reversed these effects of ethanol. Conclusion: Ethanol ingestion prior to and during pregnancy perturbed AM zinc balance resulting in impaired bacterial clearance, but these effects were ameliorated by in vitro zinc treatments. PMID:25371044

  11. Culture of fetal alveolar epithelial type II cells in serum-free medium.

    PubMed

    Fraslon, C; Rolland, G; Bourbon, J R; Rieutort, M; Valenza, C

    1991-11-01

    A serum-free culture medium (defined medium = DM) was elaborated by adding to Eagle's minimum essential medium (MEM), non-essential amino acids, transferrin, putrescine, tripeptide glycyl-histidyl-lysine, somatostatin, sodium selenite, ethanolamine, phosphoethanolamine, sodium pyruvate, and metal trace elements. This medium was tested for its ability to support sustained surfactant biosynthesis in fetal alveolar epithelial type II cells. For up to 8 days, ultrastructure was maintained with persistence of lamellar inclusion bodies. Thymidine incorporation into DNA was enhanced about 50% in DM as compared with MEM, whereas it was enhanced 300% in 10% fetal bovine serum. With DM, the incorporation of tritiated choline into phosphatidylcholine (PC) of isolated surfactant material was about twice that with MEM. Deletion experiments evidenced the prominent role of pyruvate, transferrin, and selenium in the stimulation of surfactant PC biosynthesis. The addition of biotin to DM enhanced surfactant PC biosynthesis slightly and nonsurfactant PC biosynthesis markedly. The presence of nucleosides seemed unfavorable to the synthesis of surfactant PC. Type II cells responded to the addition of epidermal growth factor and insulinlike growth factor-I both by increased thymidine incorporation into DNA and choline incorporation into PC. It is concluded that DM represents a useful tool for cultivating type II cells without loss of their specialized properties and for studying the regulation of cell proliferation and surfactant biosynthesis in a controlled environment. PMID:1748624

  12. Relationship of structural to functional impairment during alveolar-capillary membrane development.

    PubMed

    Ahlfeld, Shawn K; Gao, Yong; Conway, Simon J; Tepper, Robert S

    2015-04-01

    Bronchopulmonary dysplasia is a chronic lung disease of extreme preterm infants and results in impaired gas exchange. Although bronchopulmonary dysplasia is characterized histologically by alveolar-capillary simplification in animal models, it is clinically defined by impaired gas diffusion. With the use of a developmentally relevant model, we correlated alveolar-capillary structural simplification with reduced functional gas exchange as measured by the diffusing factor for carbon monoxide (DFCO). Neonatal mouse pups were exposed to >90% hyperoxia or room air during postnatal days 0 to 7, and then all pups were returned to room air from days 7 to 56. At day 56, DFCO was measured as the ratio of carbon monoxide uptake to neon dilution, and lungs were fixed for histologic assessment of alveolar-capillary development. Neonatal hyperoxia exposure inhibited alveolar-capillary septal development as evidenced by significantly increased mean linear intercept, increased airspace-to-septal ratio, decreased nodal density, and decreased pulmonary microvasculature. Importantly, alveolar-capillary structural deficits in hyperoxia-exposed pups were accompanied by a significant 28% decrease in DFCO (0.555 versus 0.400; P < 0.0001). In addition, DFCO was highly and significantly correlated with structural measures of reduced alveolar-capillary growth. Simplification of alveolar-capillary structure is highly correlated with impaired gas exchange function. Current mechanistic and therapeutic animal models of inhibited alveolar development may benefit from application of DFCO as an alternative physiologic indicator of alveolar-capillary development. PMID:25661110

  13. Epithelial β1 integrin is required for lung branching morphogenesis and alveolarization.

    PubMed

    Plosa, Erin J; Young, Lisa R; Gulleman, Peter M; Polosukhin, Vasiliy V; Zaynagetdinov, Rinat; Benjamin, John T; Im, Amanda M; van der Meer, Riet; Gleaves, Linda A; Bulus, Nada; Han, Wei; Prince, Lawrence S; Blackwell, Timothy S; Zent, Roy

    2014-12-01

    Integrin-dependent interactions between cells and extracellular matrix regulate lung development; however, specific roles for β1-containing integrins in individual cell types, including epithelial cells, remain incompletely understood. In this study, the functional importance of β1 integrin in lung epithelium during mouse lung development was investigated by deleting the integrin from E10.5 onwards using surfactant protein C promoter-driven Cre. These mutant mice appeared normal at birth but failed to gain weight appropriately and died by 4 months of age with severe hypoxemia. Defects in airway branching morphogenesis in association with impaired epithelial cell adhesion and migration, as well as alveolarization defects and persistent macrophage-mediated inflammation were identified. Using an inducible system to delete β1 integrin after completion of airway branching, we showed that alveolarization defects, characterized by disrupted secondary septation, abnormal alveolar epithelial cell differentiation, excessive collagen I and elastin deposition, and hypercellularity of the mesenchyme occurred independently of airway branching defects. By depleting macrophages using liposomal clodronate, we found that alveolarization defects were secondary to persistent alveolar inflammation. β1 integrin-deficient alveolar epithelial cells produced excessive monocyte chemoattractant protein 1 and reactive oxygen species, suggesting a direct role for β1 integrin in regulating alveolar homeostasis. Taken together, these studies define distinct functions of epithelial β1 integrin during both early and late lung development that affect airway branching morphogenesis, epithelial cell differentiation, alveolar septation and regulation of alveolar homeostasis. PMID:25395457

  14. Further examination of alveolar septal adaptation to left pneumonectomy in the adult lung.

    PubMed

    Hsia, Connie C W; Johnson, Robert L

    2006-04-28

    Recent data from our laboratory are presented concerning alveolar septal adaptation following 42-45% lung resection by left pneumonectomy (PNX) in adult foxhounds compared to sham-operated control animals. Results confirm our previous conclusion that compensation in the remaining lung occurs without a net growth of additional alveolar septal tissue. The major ultrastructural responses are (a) alveolar capillary distention, which recruits capillary blood volume and surface area, leading to a 30-50% increase in lung diffusing capacity estimated by morphometry, a magnitude similar to that measured by physiologic methods; (b) a selectively increased volume of type 2 alveolar epithelial cells. These data, taken together with the balanced compensatory growth of alveolar septal cells observed in adult dogs following 55-58% lung resection by right PNX, support a graded alveolar cellular response to chronic mechanical strain with the alveolar epithelial cells being activated first; as strain increases further with greater lung resection other alveolar cells also become activated leading to an overt increase in septal tissue volume. The spatial distribution of lobar mechanical strain and lobar tissue volume assessed by high resolution computed tomography was markedly non-uniform after PNX, suggesting possible non-uniform distribution of alveolar cellular response. The sequential activation of physiologic recruitment and cellular adaptation confer additive functional benefits that optimize long-term exercise performance after PNX. PMID:16563882

  15. Minimum Bayes risk image correlation

    NASA Technical Reports Server (NTRS)

    Minter, T. C., Jr.

    1980-01-01

    In this paper, the problem of designing a matched filter for image correlation will be treated as a statistical pattern recognition problem. It is shown that, by minimizing a suitable criterion, a matched filter can be estimated which approximates the optimum Bayes discriminant function in a least-squares sense. It is well known that the use of the Bayes discriminant function in target classification minimizes the Bayes risk, which in turn directly minimizes the probability of a false fix. A fast Fourier implementation of the minimum Bayes risk correlation procedure is described.

  16. Ceramic veneers with minimum preparation

    PubMed Central

    da Cunha, Leonardo Fernandes; Reis, Rachelle; Santana, Lino; Romanini, Jose Carlos; Carvalho, Ricardo Marins; Furuse, Adilson Yoshio

    2013-01-01

    The aim of this article is to describe the possibility of improving dental esthetics with low-thickness glass ceramics without major tooth preparation for patients with small to moderate anterior dental wear and little discoloration. For this purpose, a carefully defined treatment planning and a good communication between the clinician and the dental technician helped to maximize enamel preservation, and offered a good treatment option. Moreover, besides restoring esthetics, the restorative treatment also improved the function of the anterior guidance. It can be concluded that the conservative use of minimum thickness ceramic laminate veneers may provide satisfactory esthetic outcomes while preserving the dental structure. PMID:24932126

  17. Resistance minimum and heavy fermions.

    PubMed

    Jun, Kondo

    2006-12-01

    The phenomenon of the resistance minimum in dilute magnetic alloys is explained in terms of the s-d interaction which takes account of scattering of the conduction electron off the magnetic impurities in metals. Some of the intermetallic compounds which involve rare earth elements or uranium show a very large electronic specific heat and remain non-magnetic even though they show a Curie-like susceptibility at higher temperatures. These phenomena are also explained based on the s-d interaction model. PMID:25792794

  18. Resistance minimum and heavy fermions

    PubMed Central

    Jun, Kondo

    2006-01-01

    The phenomenon of the resistance minimum in dilute magnetic alloys is explained in terms of the s-d interaction which takes account of scattering of the conduction electron off the magnetic impurities in metals. Some of the intermetallic compounds which involve rare earth elements or uranium show a very large electronic specific heat and remain non-magnetic even though they show a Curie-like susceptibility at higher temperatures. These phenomena are also explained based on the s-d interaction model. PMID:25792794

  19. [The biological monitoring of occupational exposure to anesthetic gas and vapors: the determination of nitrogen protoxide, halothane and isoflurane in the urine].

    PubMed

    Buratti, M; Pellegrino, O; Valla, C; Colombi, A

    1993-01-01

    A gas-chromatographic method has been developed for measuring urinary nitrous oxide, halothane and isoflurane concentrations. A volume of head-space gases obtained from biological samples is analyzed by ECD-GC on a steel column (2 mm ID) serially packed with Porapak Q (1.2 m) and MS-5A (0.30 m), operated at 160 degrees C. The detection limit (ranging from 0.03 micrograms/l for halothane to 1 microgram/l for nitrous oxide), between-day precision (CV < 6%) and working linear range (up to 100 micrograms/l for halothane and 2000 micrograms/l for nitrous oxide) were determined. A two-year experience in biological monitoring of occupationally exposed surgical staff with the proposed method is reported and confounding factors are discussed. The method is easy to perform, free from interferences and suitable for use in routine analysis in toxicological laboratories. PMID:8492738

  20. Neuroprotective properties of vitamin C on equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in high fat diet fed neonatal mice

    PubMed Central

    Xu, Kai-Xiang; Tao, Jun; Zhang, Nan; Wang, Jian-Zhong

    2015-01-01

    Obesity has been reported to be one of the significant contributors to various chronic disease conditions. Childhood obesity has been on an alarming increase over recent years leading to various health complications. Millions of children undergo surgery each year as a part of medical care on various health grounds. In the present study, influence of vitamin C on the effect of obesity and over-weight under anaesthetic exposure was analysed. Separate groups of neonatal mice (C57BL/6) were fed on high-fat diet to induce obesity. The mice were administered with vitamin C at 30 and 60 mg/kg b.wt post natal day 1 (P1) to P21. P7 mice were exposed to equipotent doses of isoflurane or sevoflurane or desflurane. Neuroapoptosis was assessed by measuring activated caspase-3 and TUNEL assay. Plasma S100β levels were detected by ELISA. The mice were assessed for their general behaviour. Morris water maze test was performed to assess the spatial working memory. Anesthesia exposure caused severe neuroapoptosis and also raised the levels of plasma S100β. Neuroapotosis, working memory and learning impairments observed following anesthetics were comparatively more profound on high fat diet fed mice. Desflurane exposure resulted in higher apoptotic counts, learning and memory deficits than equipotent dose of isoflurane and sevoflurane. Vitamin C supplementation offered significant protection against anesthetic induced neurotoxicity and behavioural alterations. Vitamin C administration resulted in marked reduction in neurotoxicity induced by anesthesia and as well improved learning and memory of both normal and high fat diet fed mice. PMID:26379835

  1. Cardiopulmonary effects of thiopental versus propofol as an induction agent prior to isoflurane anesthesia in chair trained rhesus macaques (Macaca mulatta)

    PubMed Central

    Choi, Yun-Jung; Park, Hye-Jin; Kim, Hyeon-Ho; Lee, Yun-Jin; Jung, Kyeong-Cheon; Park, Seong-Hoe

    2016-01-01

    The purpose of this study was to evaluate the effects of thiopental versus propofol on cardiopulmonary functions, when used as an induction agent prior to isoflurane anesthesia in rhesus monkeys. Eight healthy rhesus monkeys weighing 3.72 to 5.7 kg, 4-5 years old, were used in the study. Anesthesia was induced with thiopental or propofol intravenous injection, and then maintained with isoflurane in oxygen for 45 minutes. Cardiopulmonary measurements were obtained before and 5, 15, 30, 45, and 60 minutes after induction. The induction doses of thiopental and propofol were 19.41±0.54 and 9.33±1.02 mg/kg, respectively. In both groups, the values of heart rate, respiratory rate, temperature, systolic blood pressure, mean blood pressure, diastolic blood pressure, pH, and lactate were decreased, while the values of partial pressure of carbon dioxide, partial pressure of oxygen, total carbon dioxide, bicarbonate, oxygen saturation, and base excess in the extracellular fluid were increased, as compared with baseline. Systolic blood pressure was significantly lower in thiopental group compare to propofol group. Induction time was very short in both agents but not revealed a significant difference between both groups. However, recovery time was extremely faster in the propofol group. Our results demonstrated that propofol provides a minor suppression in systolic arterial blood pressure than thiopental sodium. In addition, propofol have a fast recovery effect from the anesthesia as well. Furthermore, it is suggested that thiopental sodium could also be used to induce anesthesia instead of propofol, despite slight more suppression of cardiopulmonary function compared to thiopental sodium. PMID:27051438

  2. Cardiopulmonary effects of thiopental versus propofol as an induction agent prior to isoflurane anesthesia in chair trained rhesus macaques (Macaca mulatta).

    PubMed

    Choi, Yun-Jung; Park, Hye-Jin; Kim, Hyeon-Ho; Lee, Yun-Jin; Jung, Kyeong-Cheon; Park, Seong-Hoe; Lee, Jae-Il

    2016-03-01

    The purpose of this study was to evaluate the effects of thiopental versus propofol on cardiopulmonary functions, when used as an induction agent prior to isoflurane anesthesia in rhesus monkeys. Eight healthy rhesus monkeys weighing 3.72 to 5.7 kg, 4-5 years old, were used in the study. Anesthesia was induced with thiopental or propofol intravenous injection, and then maintained with isoflurane in oxygen for 45 minutes. Cardiopulmonary measurements were obtained before and 5, 15, 30, 45, and 60 minutes after induction. The induction doses of thiopental and propofol were 19.41±0.54 and 9.33±1.02 mg/kg, respectively. In both groups, the values of heart rate, respiratory rate, temperature, systolic blood pressure, mean blood pressure, diastolic blood pressure, pH, and lactate were decreased, while the values of partial pressure of carbon dioxide, partial pressure of oxygen, total carbon dioxide, bicarbonate, oxygen saturation, and base excess in the extracellular fluid were increased, as compared with baseline. Systolic blood pressure was significantly lower in thiopental group compare to propofol group. Induction time was very short in both agents but not revealed a significant difference between both groups. However, recovery time was extremely faster in the propofol group. Our results demonstrated that propofol provides a minor suppression in systolic arterial blood pressure than thiopental sodium. In addition, propofol have a fast recovery effect from the anesthesia as well. Furthermore, it is suggested that thiopental sodium could also be used to induce anesthesia instead of propofol, despite slight more suppression of cardiopulmonary function compared to thiopental sodium. PMID:27051438

  3. Effects of alveolar ridge preservation on delayed implant osseointegration

    PubMed Central

    Shao, Shan; Li, Bin; Xue, Hui-Min; Huang, Hai-Yun; Liu, Gang-Li

    2015-01-01

    To evaluate the effects of alveolar ridge preservation with Bio-Oss bone substitute (Geistlich Pharma) on delayed implant osseointegration. The 3rd and 4th left and right mandibular premolars were extracted from four adult healthy male and female dogs. For the experimental group, we randomly selected two extraction sockets in each dog to be filled with Bio-Oss bone substitute (Geistlich Pharma). The two remaining extraction sockets remained untreated and served as the control group. Three months after Bio-Oss placement, dental implants were inserted into the alveolar bone of the experimental group and the control group. The osteogenic activity of the bone around the implants was assessed by evaluating the histological morphology and by estimating histomorphometric parameters at 3 and 6 months after delayed implantation. At 3 months, Goldner’s trichrome staining analysis showed that the bone-implant contact rate and mineralised bone area around the implant were significantly higher in the experimental group (75.98% ± 8.97% and 69.52% ± 9.63%, respectively) than in the control group (56.13% ± 8.18% and 52.82% ± 7.25%, respectively; P < 0.05). However, at 6 months, the two groups showed no significant difference. Fluorescence microscopy analysis revealed that the average mineralisation apposition rate of the bone tissue around the dental implant in the experimental group at 3 and 6 months was 6.80 ± 0.43 μm and 8.38 ± 0.84 μm, respectively, which was significantly higher than the rate in the control group (P < 0.05). These data indicated that alveolar ridge preservation by using Bio-Oss placement can promote osseointegration of delayed implantation. This may be a promising option for clinical use. PMID:26379871

  4. Autoimmune pulmonary alveolar proteinosis: clinical course and diagnostic criteria.

    PubMed

    Ben-Dov, Issahar; Segel, Michael J

    2014-01-01

    Pulmonary alveolar proteinosis (PAP) is caused by accumulation of surfactant components in the alveoli and terminal airways. All forms of PAP are caused by insufficient surfactant clearance by alveolar macrophages. Autoimmune PAP, a rare, antibody-mediated disease, that compromises 90% of cases of PAP, is causes by IgG autoantibodies that block GM-CSF effect, a crucial step for macrophage maturation. Alveolar filling may progress to respiratory insufficiency, but the course of the disease is variable. Patients usually complain of dyspnea, mainly with exertion, and cough. Chest CT shows highly suggestive ground grass opacification crossed by heavy septal lines, leading to the typical "crazy paving" appearance. Bronchoalveolar lavage reveals "milky" fluid, containing semisolid remnants of surfactant components, packed as lamellar bodies. The surfactant appears granular and pink on PAS staining, and lung architecture is preserved. These cytological and pathological characteristics are diagnostic for PAP. In addition, a high titer of IgG anti GM-CSF autoantibodies is highly sensitive and specific for the diagnosis. The trigger for antibodies formation and their role (if any) in regulation GM-CSF activity in the normal state are unknown. Based on the specificity of these characteristics we suggest a structured framework for the diagnosis of Autoimmune PAP. Lung lavage with a large volume of saline is the standard therapy, and is effective in most patients. However, immune-modulatory therapy, by either supplying exogenous GM-CSF, or by inhibiting the CD20+ antibody forming cells, with Rituximab, is also effective in many patients. The precise role of each therapy, alone or in combination, should be systematically studied. PMID:24424195

  5. Proposal of a computed tomography classification for hepatic alveolar echinococcosis

    PubMed Central

    Graeter, Tilmann; Kratzer, Wolfgang; Oeztuerk, Suemeyra; Haenle, Mark Martin; Mason, Richard Andrew; Hillenbrand, Andreas; Kull, Thomas; Barth, Thomas F; Kern, Peter; Gruener, Beate

    2016-01-01

    AIM: To establish a computed tomography (CT)-morphological classification for hepatic alveolar echinococcosis was the aim of the study. METHODS: The CT morphology of hepatic lesions in 228 patients with confirmed alveolar echinococcosis (AE) drawn from the Echinococcus Databank of the University Hospital of Ulm was reviewed retrospectively. For this reason, CT datasets of combined positron emission tomography (PET)-CT examinations were evaluated. The diagnosis of AE was made in patients with unequivocal seropositivity; positive histological findings following diagnostic puncture or partial resection of the liver; and/or findings typical for AE at either ultrasonography, CT, magnetic resonance imaging or PET-CT. The CT-morphological findings were grouped into the new classification scheme. RESULTS: Within the classification a lesion was dedicated to one out of five “primary morphologies” as well as to one out of six “patterns of calcification”. “primary morphology” and “pattern of calcification” are primarily focussed on separately from each other and combined, whereas the “primary morphology” V is not further characterized by a “pattern of calcification”. Based on the five primary morphologies, further descriptive sub-criteria were appended to types I-III. An analysis of the calcification pattern in relation to the primary morphology revealed the exclusive association of the central calcification with type IV primary morphology. Similarly, certain calcification patterns exhibited a clear predominance for other primary morphologies, which underscores the delimitation of the individual primary morphological types from each other. These relationships in terms of calcification patterns extend into the primary morphological sub-criteria, demonstrating the clear subordination of those criteria. CONCLUSION: The proposed CT-morphological classification (EMUC-CT) is intended to facilitate the recognition and interpretation of lesions in hepatic

  6. Metabolic shift in lung alveolar cell mitochondria following acrolein exposure.

    PubMed

    Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

    2013-11-15

    Acrolein, an α,β unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A2 activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants. PMID:24056970

  7. Notch signaling promotes airway mucous metaplasia and inhibits alveolar development.

    PubMed

    Guseh, J Sawalla; Bores, Sam A; Stanger, Ben Z; Zhou, Qiao; Anderson, William J; Melton, Douglas A; Rajagopal, Jayaraj

    2009-05-01

    The airways are conduits that transport atmospheric oxygen to the distal alveolus. Normally, airway mucous cells are rare. However, diseases of the airway are often characterized by mucous metaplasia, in which there are dramatic increases in mucous cell numbers. As the Notch pathway is known to regulate cell fate in many contexts, we misexpressed the active intracellular domain of the mouse Notch1 receptor in lung epithelium. Notch misexpression resulted in an increase in mucous cells and a decrease in ciliated cells in the airway. Similarly, mouse embryonic tracheal explants and adult human airway epithelium treated with Notch agonists displayed increased mucous cell numbers and decreased ciliated cell numbers. Notch antagonists had the opposite effect. Notably, Notch antagonists blocked IL13-induced mucous metaplasia. IL13 has a well-established role as an inflammatory mediator of mucous metaplasia and functions through Stat6-mediated gene transcription. We found that Notch ligands, however, are able to cause mucous metaplasia in Stat6-null cultured trachea, thus identifying a novel pathway that stimulates mucous metaplasia. Notch signaling may therefore play an important role in airway disease and, by extension, Notch antagonists may have therapeutic value. Conversely, in the distal lung, Notch misexpression prevented the differentiation of alveolar cell types. Instead, the distal lung formed cysts composed of cells that were devoid of alveolar markers but that expressed some, but not all, markers of proximal airway epithelium. Occasional distal cystic cells appeared to differentiate into normal proximal airway cells, suggesting that ectopic Notch signaling arrests the normal differentiation of distal lung progenitors before they initiate an alveolar program. PMID:19369400

  8. Effect of Alveolar Ridge Preservation after Tooth Extraction

    PubMed Central

    Avila-Ortiz, G.; Elangovan, S.; Kramer, K.W.O.; Blanchette, D.; Dawson, D.V.

    2014-01-01

    Alveolar ridge preservation strategies are indicated to minimize the loss of ridge volume that typically follows tooth extraction. The aim of this systematic review was to determine the effect that socket filling with a bone grafting material has on the prevention of postextraction alveolar ridge volume loss as compared with tooth extraction alone in nonmolar teeth. Five electronic databases were searched to identify randomized clinical trials that fulfilled the eligibility criteria. Literature screening and article selection were conducted by 3 independent reviewers, while data extraction was performed by 2 independent reviewers. Outcome measures were mean horizontal ridge changes (buccolingual) and vertical ridge changes (midbuccal, midlingual, mesial, and distal). The influence of several variables of interest (i.e., flap elevation, membrane usage, and type of bone substitute employed) on the outcomes of ridge preservation therapy was explored via subgroup analyses. We found that alveolar ridge preservation is effective in limiting physiologic ridge reduction as compared with tooth extraction alone. The clinical magnitude of the effect was 1.89 mm (95% confidence interval [CI]: 1.41, 2.36; p < .001) in terms of buccolingual width, 2.07 mm (95% CI: 1.03, 3.12; p < .001) for midbuccal height, 1.18 mm (95% CI: 0.17, 2.19; p = .022) for midlingual height, 0.48 mm (95% CI: 0.18, 0.79; p = .002) for mesial height, and 0.24 mm (95% CI: –0.05, 0.53; p = .102) for distal height changes. Subgroup analyses revealed that flap elevation, the usage of a membrane, and the application of a xenograft or an allograft are associated with superior outcomes, particularly on midbuccal and midlingual height preservation. PMID:24966231

  9. A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking

    PubMed Central

    Woodruff, Prescott G.; Koth, Laura L.; Yang, Yee Hwa; Rodriguez, Madeleine W.; Favoreto, Silvio; Dolganov, Gregory M.; Paquet, Agnes C.; Erle, David J.

    2005-01-01

    Rationale: Macrophages are believed to play a central role in emphysema based largely on data from mouse models. However, the relevance of these models to smoking-related lung disease in humans is uncertain. Objectives: We sought to comprehensively characterize the effects of smoking on gene expression in human alveolar macrophages and to compare these with effects seen in transgenic mouse models of emphysema. Methods: We used DNA microarrays with genomewide coverage to analyze alveolar macrophages from 15 smokers, 15 nonsmokers, and 15 subjects with asthma (disease control). Selected gene expression changes were validated by polymerase chain reaction and ELISA. Expression changes were compared with those identified by microarray analysis of interleukin-13–overexpressing and integrin-β6–deficient mice, which both develop emphysema. Measurements and Main Results: All 15 smokers shared a common pattern of macrophage gene expression that distinguished them from nonsmokers, a finding not observed in subjects with asthma. We identified 110 genes as differentially expressed in smokers despite using conservative statistical methods. Matrix metalloproteinase 12, a proteinase that plays a critical role in mouse models, was the third most highly induced gene in smokers (ninefold, p < 0.0001). However, most changes in smokers were not reflected in mouse models. One such finding was increased osteopontin expression in smokers (fourfold, p = 0.006), which was confirmed at the protein level and correlated with the degree of airway obstruction. Conclusions: Smoking induces a remarkably consistent and distinctive pattern of alveolar macrophage activation. These studies identify aspects of mouse models that are directly relevant to human smokers and also reveal novel potential mediators of smoking-related diseases. PMID:16166618

  10. Prediction of the alveolar bone level after the extraction of maxillary anterior teeth with severe periodontitis

    PubMed Central

    2015-01-01

    Purpose After extraction, the alveolar bone tends to undergo atrophy in three-dimensions. The amount of alveolar bone loss in the horizontal dimension has been reported to be greater than the amount of bone loss in the vertical dimension, and is most pronounced in the buccal aspect. The aim of this study was to monitor the predictive alveolar bone level following the extraction of anterior teeth seriously involved with advanced chronic periodontitis. Methods This study included 25 patients with advanced chronic periodontitis, whose maxillary anterior teeth had been extracted due to extensive attachment loss more than one year before the study. Periapical radiographs were analyzed to assess the vertical level of alveolar bone surrounding the edentulous area. An imaginary line connecting the mesial and the distal ends of the alveolar crest facing the adjacent tooth was arbitrarily created. Several representative coordinates were established in the horizontal direction, and the vertical distance from the imaginary line to the alveolar crest was measured at each coordinate for each patient using image analysis software. Regression functions predicting the vertical level of the alveolar bone in the maxillary anterior edentulous area were identified for each patient. Results The regression functions demonstrated a tendency to converge to parabolic shapes. The predicted maximum distance between the imaginary line and the alveolar bone calculated using the regression function was 1.43±0.65 mm. No significant differences were found between the expected and actual maximum distances. Likewise, the predicted and actual maximum horizontal distances did not show any significant differences. The distance from the alveolar bone crest to the imaginary lines was not influenced by the mesio-distal spans of the edentulous area. Conclusions After extraction, the vertical level of the alveolar ridge increased to become closer to the reference line connecting the mesial and distal

  11. Pulmonary alveolar proteinosis: another autoimmune disease associated with sarcoidosis?

    PubMed

    Boerner, Eda Burcu; Costabel, Ulrich; Wessendorf, Thomas Ernst; Theegarten, Dirk; Hetzel, Martin; Drent, Marjolein; Bonella, Francesco

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of surfactant phospholipids and lipoproteins within the alveoli.  Here we report on a female patient who was diagnosed with autoimmune PAP and successfully treated with whole lung lavage (WLL). 15 months after PAP diagnosis the patient developed marked fatigue. Additional tests revealed the diagnosis of sarcoidosis. We can only speculate that PAP and sarcoidosis in our patient are linked to each other based on the fact that other autoimmune disorders have also been associated with sarcoidosis. PMID:27055841

  12. A 3-step therapeutic strategy for severe alveolar proteinosis.

    PubMed

    Noirez, Leslie; Koutsokera, Angela; Pantet, Olivier; Duss, François-Régis; Eggimann, Philippe; Tozzi, Piergiorgio; Gonzalez, Michel; Coronado, Marcos; Nicod, Laurent P; Lovis, Alban

    2015-04-01

    Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of lipoproteinaceous material in the terminal airways. Whole lung lavage (WLL) remains the gold standard treatment but may be particularly challenging in cases of severe hypoxemia. We present a 3-step strategy that was used in a patient with PAP-associated refractory hypoxemia and that combined venovenous extracorporeal membrane oxygenation (vvECMO), double-lumen orotracheal intubation, and bilateral multisegmental sequential lavage (MSL). The procedure was well tolerated and permitted weaning from the ventilator. PMID:25841841

  13. Alveolar hemorrhage after scuba diving: a case report.

    PubMed

    Tsai, Ming-Ju; Tsai, Mee-Sun; Tsai, Ying-Ming; Lien, Chi-Tun; Hwang, Jhi-Jhu; Huang, Ming-Shyan

    2010-07-01

    Self-contained underwater breathing apparatus (scuba) diving is increasingly popular in Taiwan. There are few references in the literature regarding pulmonary hemorrhage as the sole manifestation of pulmonary barotrauma in scuba divers, and no study from Taiwan was found in the literature. We present the case of a 25-year-old man who suffered alveolar hemorrhage related to pulmonary barotrauma as a complication of scuba diving. To our knowledge, this is the first case report describing a Taiwanese subject suffering from non-fatal pulmonary hemorrhage after scuba diving. PMID:20638043

  14. Pulmonary alveolar proteinosis in children: a case series

    PubMed Central

    Tabatabaei, Seyyed Ahmad; Karimi, Abdollah; Tabatabaei, Sedigheh Rafiee; Radpay, Badiozzaman; Jadali, Farzaneh; Shiva, Farideh; Jahromy, Mana Hadipour

    2010-01-01

    Pulmonary alveolar proteinosis, (PAP) is a rare disease of unknown etiology, characterized by accumulation of intraalveolar proteinaceous material which is rich in lipid and positive on periodic acid-Schiff stain. Two clinically different pediatric types have been defined as congenital PAP which is fulminant and fatal, and a late-onset PAP which is similar to the adult form and less severe. Eight children with late-onset PAP were hospitalized from 1998 to 2005 in Mofid Children Hospital. Characteristics of these patients and the methods of diagnosis and treatment are presented in this case series. PMID:21526069

  15. Bruxism elicited by inferior alveolar nerve injury: a case report.

    PubMed

    Melis, Marcello; Coiana, Carlo; Secci, Simona

    2012-02-01

    The aim of this case report is to describe the history of a patient who received an injury to the right inferior alveolar nerve after placement of a dental implant, with bruxism noted afterward. The symptoms were managed by the use of an occlusal appliance worn at night and occasionally during the day, associated with increased awareness of parafunction during the day to reduce muscle pain and fatigue. Paresthesia of the teeth, gingiva, and lower lip persisted but were reduced during appliance use. PMID:22254232

  16. Nocardial brain abscess in a patient with pulmonary alveolar proteinosis.

    PubMed

    Shirani, Kiana; Poulsen, Asger Nyborg; Hakamifard, Atousa

    2015-01-01

    Brain abscesses caused by Nocardia are rare but have a very high mortality and specific requirements of antibiotic treatment. Nocardial brain abscesses are mainly found in patients with predisposing conditions such as pulmonary alveolar proteinosis (PAP), a disease associated with chronic exposure to silica dust. We present a case of multiple nocardial brain abscesses in a man with PAP probably due to long-term occupational exposure to silica dust. Conclusively, in patients presenting brain abscesses and a history of chronic exposure to silica dust, PAP and opportunistic nocardial infection should always be considered as possible diagnoses. PMID:26605224

  17. Nocardial brain abscess in a patient with pulmonary alveolar proteinosis

    PubMed Central

    Shirani, Kiana; Poulsen, Asger Nyborg; Hakamifard, Atousa

    2015-01-01

    Brain abscesses caused by Nocardia are rare but have a very high mortality and specific requirements of antibiotic treatment. Nocardial brain abscesses are mainly found in patients with predisposing conditions such as pulmonary alveolar proteinosis (PAP), a disease associated with chronic exposure to silica dust. We present a case of multiple nocardial brain abscesses in a man with PAP probably due to long-term occupational exposure to silica dust. Conclusively, in patients presenting brain abscesses and a history of chronic exposure to silica dust, PAP and opportunistic nocardial infection should always be considered as possible diagnoses. PMID:26605224

  18. Does the Minimum Wage Affect Welfare Caseloads?

    ERIC Educational Resources Information Center

    Page, Marianne E.; Spetz, Joanne; Millar, Jane

    2005-01-01

    Although minimum wages are advocated as a policy that will help the poor, few studies have examined their effect on poor families. This paper uses variation in minimum wages across states and over time to estimate the impact of minimum wage legislation on welfare caseloads. We find that the elasticity of the welfare caseload with respect to the…

  19. Do Some Workers Have Minimum Wage Careers?

    ERIC Educational Resources Information Center

    Carrington, William J.; Fallick, Bruce C.

    2001-01-01

    Most workers who begin their careers in minimum-wage jobs eventually gain more experience and move on to higher paying jobs. However, more than 8% of workers spend at least half of their first 10 working years in minimum wage jobs. Those more likely to have minimum wage careers are less educated, minorities, women with young children, and those…

  20. 43 CFR 3923.10 - Minimum bid.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Minimum bid. 3923.10 Section 3923.10 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) OIL SHALE LEASING Minimum Bid § 3923.10 Minimum bid....

  1. 43 CFR 3923.10 - Minimum bid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Minimum bid. 3923.10 Section 3923.10 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL SHALE LEASING Minimum Bid § 3923.10 Minimum...

  2. 77 FR 32444 - Minimum Internal Control Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-01

    ... Minimum Internal Control Standards. 64 FR 590. The rule added a new part to the Commission's regulations... National Indian Gaming Commission 25 CFR Part 543 RIN 3141-AA27 Minimum Internal Control Standards AGENCY... (NIGC) proposes to amend its minimum internal control standards for Class II gaming under the...

  3. 78 FR 63873 - Minimum Internal Control Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... NIGC published a final rule in the Federal Register called Minimum Internal Control Standards. 64 FR... National Indian Gaming Commission 25 CFR Part 543 RIN 3141-AA27 Minimum Internal Control Standards AGENCY... Commission (NIGC) amends its minimum internal control standards for Class II gaming under the Indian...

  4. 30 CFR 202.53 - Minimum royalty.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Minimum royalty. 202.53 Section 202.53 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT ROYALTIES Oil, Gas, and OCS Sulfur, General § 202.53 Minimum royalty. For leases that provide for minimum...

  5. Minimum variance beamformer weights revisited.

    PubMed

    Moiseev, Alexander; Doesburg, Sam M; Grunau, Ruth E; Ribary, Urs

    2015-10-15

    Adaptive minimum variance beamformers are widely used analysis tools in MEG and EEG. When the target brain activity presents in the form of spatially localized responses, the procedure usually involves two steps. First, positions and orientations of the sources of interest are determined. Second, the filter weights are calculated and source time courses reconstructed. This last step is the object of the current study. Despite different approaches utilized at the source localization stage, basic expressions for the weights have the same form, dictated by the minimum variance condition. These classic expressions involve covariance matrix of the measured field, which includes contributions from both the sources of interest and the noise background. We show analytically that the same weights can alternatively be obtained, if the full field covariance is replaced with that of the noise, provided the beamformer points to the true sources precisely. In practice, however, a certain mismatch is always inevitable. We show that such mismatch results in partial suppression of the true sources if the traditional weights are used. To avoid this effect, the "alternative" weights based on properly estimated noise covariance should be applied at the second, source time course reconstruction step. We demonstrate mathematically and using simulated and real data that in many situations the alternative weights provide significantly better time course reconstruction quality than the traditional ones. In particular, they a) improve source-level SNR and yield more accurately reconstructed waveforms; b) provide more accurate estimates of inter-source correlations; and c) reduce the adverse influence of the source correlations on the performance of single-source beamformers, which are used most often. Importantly, the alternative weights come at no additional computational cost, as the structure of the expressions remains the same. PMID:26143207

  6. Is there a relation between local bone quality as assessed on panoramic radiographs and alveolar bone level?

    PubMed

    Nackaerts, Olivia; Gijbels, Frieda; Sanna, Anna-Maria; Jacobs, Reinhilde

    2008-03-01

    The aim was to explore the relation between radiographic bone quality on panoramic radiographs and relative alveolar bone level. Digital panoramic radiographs of 94 female patients were analysed (mean age, 44.5; range, 35-74). Radiographic density of the alveolar bone in the premolar region was determined using Agfa Musica software. Alveolar bone level and bone quality index (BQI) were also assessed. Relationships between bone density and BQI on one hand and the relative loss of alveolar bone level on the other were assessed. Mandibular bone density and loss of alveolar bone level were weakly but significantly negatively correlated for the lower premolar area (r = -.27). The BQI did not show a statistically significant relation to alveolar bone level. Radiographic mandibular bone density on panoramic radiographs shows a weak but significant relation to alveolar bone level, with more periodontal breakdown for less dense alveolar bone. PMID:17690924

  7. Retinoic acid promotes primary fetal alveolar epithelial type II cell proliferation and differentiation to alveolar epithelial type I cells.

    PubMed

    Gao, Rui-wei; Kong, Xiang-yong; Zhu, Xiao-xi; Zhu, Guo-qing; Ma, Jin-shuai; Liu, Xiu-xiang

    2015-05-01

    Retinoic acid (RA) plays an important role in lung development and maturation. Many stimuli can induce alveolar epithelial cell damage which will result in the injury of lung parenchyma. The aim of this study was to observe the effect of RA on the proliferation and differentiation of primary fetal alveolar epithelial type II cells (fAECIIs). Primary fAECIIs were isolated from fetal rats at 19 d of gestation and purified by a differential centrifugation and adhesion method. The cells were randomly divided into control (dimethyl sulfoxide, DMSO) and RA groups. Cell proliferation, viability, apoptosis, cycle, and expression of target protein were examined at 24, 48, and 72 h. We found that the proliferation and viability of cells in the RA-exposed group significantly increased compared with the DMSO control group. The proportion (%) of cells in the G2 and S phases in the RA group was significantly higher than that in control group cells. The proportion (%) of both early apoptotic cells and late apoptotic cells decreased significantly in cells exposed to RA compared with cells exposed to DMSO. RA significantly enhanced the expression of aquaporin 5 (AQP5). The expression level of pulmonary surfactant C (SPC) was elevated after cells were exposed to RA for 24 and 72 h but was inhibited when cells were exposed to RA for 48 h. These results suggest that RA promotes fAECII proliferation by improving cell viability, promoting S phase entry and inhibiting apoptosis and RA promotes fAECIIs differentiation to alveolar epithelial type I cells (AECIs). PMID:25515249

  8. A Rare Case of Diffuse Alveolar Hemorrhage Secondary to Acute Pulmonary Histoplasmosis

    PubMed Central

    Grover, Kunal; Zainah, Hadeel; Bhatnagar, Shubhita; Stein, Tricia

    2015-01-01

    Diffuse alveolar hemorrhage (DAH) is a rare presentation of acute pulmonary histoplasmosis. While histoplasmosis has been reported to cause hemoptysis and alveolar hemorrhage in children, the English language literature lacks any adult case reports documenting this association. We report a case of pulmonary histoplasmosis where the initial presentation was pneumonia with a subsequent diagnosis of DAH. PMID:26435863

  9. Changes in alveolar bone support induced by the Herbst appliance: a tomographic evaluation

    PubMed Central

    Schwartz, João Paulo; Raveli, Taisa Boamorte; Schwartz-Filho, Humberto Osvaldo; Raveli, Dirceu Barnabé

    2016-01-01

    ABSTRACT Objective: This study evaluated alveolar bone loss around mandibular incisors, induced by the Herbst appliance. Methods: The sample consisted of 23 patients (11 men, 12 women; mean age of 15.76 ± 1.75 years), Class II, Division 1 malocclusion, treated with the Herbst appliance. CBCT scans were obtained before treatment (T0) and after Herbst treatment (T1). Vertical alveolar bone level and alveolar bone thickness of mandibular incisors were assessed. Buccal (B), lingual (L) and total (T) bone thicknesses were assessed at crestal (1), midroot (2) and apical (3) levels of mandibular incisors. Student's t-test and Wilcoxon t-test were used to compare dependent samples in parametric and nonparametric cases, respectively. Pearson's and Spearman's rank correlation analyses were performed to determine the relationship of changes in alveolar bone thickness. Results were considered at a significance level of 5%. Results: Mandibular incisors showed no statistical significance for vertical alveolar bone level. Alveolar bone thickness of mandibular incisors significantly reduced after treatment at B1, B2, B3, T1 and significantly increased at L2. The magnitude of the statistically significant changes was less than 0.2 mm. The changes in alveolar bone thickness showed no statistical significance with incisor inclination degree. Conclusions: CBCT scans showed an association between the Herbst appliance and alveolar bone loss on the buccal surface of mandibular incisors; however, without clinical significance. PMID:27275621

  10. Genesis of amorphous calcium carbonate containing alveolar plates in the ciliate Coleps hirtus (Ciliophora, Prostomatea).

    PubMed

    Lemloh, Marie-Louise; Marin, Frédéric; Herbst, Frédéric; Plasseraud, Laurent; Schweikert, Michael; Baier, Johannes; Bill, Joachim; Brümmer, Franz

    2013-02-01

    In the protist world, the ciliate Coleps hirtus (phylum Ciliophora, class Prostomatea) synthesizes a peculiar biomineralized test made of alveolar plates, structures located within alveolar vesicles at the cell cortex. Alveolar plates are arranged by overlapping like an armor and they are thought to protect and/or stiffen the cell. Although their morphology is species-specific and of complex architecture, so far almost nothing is known about their genesis, their structure and their elemental and mineral composition. We investigated the genesis of new alveolar plates after cell division and examined cells and isolated alveolar plates by electron microscopy, energy-dispersive X-ray spectroscopy, FTIR and X-ray diffraction. Our investigations revealed an organic mesh-like structure that guides the formation of new alveolar plates like a template and the role of vesicles transporting inorganic material. We further demonstrated that the inorganic part of the alveolar plates is composed out of amorphous calcium carbonate. For stabilization of the amorphous phase, the alveolar vesicles, the organic fraction and the element phosphorus may play a role. PMID:23228488

  11. MODULATION OF HUMAN ALVEOLAR MACROPHAGE PROPERTIES BY OZONE EXPOSURE IN VITRO

    EPA Science Inventory

    We have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3) (0.1-1.0 ppm for 2-4 hours). he functions studied reflect concern that 03 is detrimental to host defense mechanisms in the broncho-alveolar spaces. xposure of HAM to cau...

  12. MORPHOMETRIC CHARACTERISTICS OF CELLS IN THE ALVEOLAR REGION OF MAMMALIAN LUNGS

    EPA Science Inventory

    Morphometric procedures have been used to study the characteristics of cells in the alveolar region of the lungs of rats, dogs, baboons, and humans. Compared with the other species, human lungs were found to contain greater numbers of macrophages and to have larger alveolar type ...

  13. Francisella tularensis replicates within alveolar type II epithelial cells in vitro and in vivo following inhalation.

    PubMed

    Hall, Joshua D; Craven, Robin R; Fuller, James R; Pickles, Raymond J; Kawula, Thomas H

    2007-02-01

    Francisella tularensis replicates in macrophages and dendritic cells, but interactions with other cell types have not been well described. F. tularensis LVS invaded and replicated within alveolar epithelial cell lines. Following intranasal inoculation of C57BL/6 mice, Francisella localized to the alveolus and replicated within alveolar type II epithelial cells. PMID:17088343

  14. Rare case report of Traumatic neuroma of anterior superior alveolar nerve associated with high frenal attachment

    PubMed Central

    Ananthaneni, Anuradha; Srilekha, Namala; Guduru, Vijay Srinivas; Kiresur, Mohammad Asif

    2015-01-01

    We present an incredible case of traumatic neuroma (TN) in the anterior superior alveolar nerve leading to the swelling in the upper labial mucosa. This paper attempts to highlight the rarity of site of occurrence of this lesion and reports the first case of TN of anterior superior alveolar nerve. PMID:25972959

  15. Regional differences in alveolar density in the human lung are related to lung height.

    PubMed

    McDonough, John E; Knudsen, Lars; Wright, Alexander C; Elliott, W Mark; Ochs, Matthias; Hogg, James C

    2015-06-01

    The gravity-dependent pleural pressure gradient within the thorax produces regional differences in lung inflation that have a profound effect on the distribution of ventilation within the lung. This study examines the hypothesis that gravitationally induced differences in stress within the thorax also influence alveolar density in terms of the number of alveoli contained per unit volume of lung. To test this hypothesis, we measured the number of alveoli within known volumes of lung located at regular intervals between the apex and base of four normal adult human lungs that were rapidly frozen at a constant transpulmonary pressure, and used microcomputed tomographic imaging to measure alveolar density (number alveoli/mm3) at regular intervals between the lung apex and base. These results show that at total lung capacity, alveolar density in the lung apex is 31.6 ± 3.4 alveoli/mm3, with 15 ± 6% of parenchymal tissue consisting of alveolar duct. The base of the lung had an alveolar density of 21.2 ± 1.6 alveoli/mm3 and alveolar duct volume fraction of 29 ± 6%. The difference in alveolar density can be negated by factoring in the effects of alveolar compression due to the pleural pressure gradient at the base of the lung in vivo and at functional residual capacity. PMID:25882386

  16. Minimum distance classification in remote sensing

    NASA Technical Reports Server (NTRS)

    Wacker, A. G.; Landgrebe, D. A.

    1972-01-01

    The utilization of minimum distance classification methods in remote sensing problems, such as crop species identification, is considered. Literature concerning both minimum distance classification problems and distance measures is reviewed. Experimental results are presented for several examples. The objective of these examples is to: (a) compare the sample classification accuracy of a minimum distance classifier, with the vector classification accuracy of a maximum likelihood classifier, and (b) compare the accuracy of a parametric minimum distance classifier with that of a nonparametric one. Results show the minimum distance classifier performance is 5% to 10% better than that of the maximum likelihood classifier. The nonparametric classifier is only slightly better than the parametric version.

  17. Alveolar hemorrhage in systemic lupus erythematosus: a cohort review.

    PubMed

    Andrade, C; Mendonça, T; Farinha, F; Correia, J; Marinho, A; Almeida, I; Vasconcelos, C

    2016-01-01

    Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%. PMID:26385219

  18. Magnetometric evaluation for the effect of chrysotile on alveolar macrophages.

    PubMed

    Keira, T; Okada, M; Katagiri, H; Aizawa, Y; Okayasu, I; Kotani, M

    1998-10-01

    Alveolar macrophages are thought to play an important role in fibrogenesis due to asbestos exposure. In this experiment, we evaluated the effect mainly by unique magnetometry and also by conventional methods such as lactate dehydrogenase (LDH) activity measurement and morphological observations. Alveolar macrophages obtained from Syrian golden hamsters by bronchoalveolar lavages were exposed 18 hours in vitro to Fe3O4 as an indicator for magnetometry and chrysotile for experiments. A rapid decrease of the remanent magnetic field, so called "relaxation", was observed after the cessation of an external magnetic field in macrophages phagocytizing Fe3O4 alone, while relaxation was delayed in those concurrently exposed to chrysotile. Since relaxation is thought due to the cytoskeleton-driven random rotation of phagosomes containing iron oxide particles, chrysotile is considered to interfere with the cytoskeletal function of macrophages. Release of LDH from chrysotile-exposed macrophages into the medium was recognized, but it was not significantly higher than the controls. Apoptosis was negligible in macrophages exposed to chrysotile by the DNA ladder detection, the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling method and morphological observations. Electron microscopical examinations revealed early necrotic changes in macrophages exposed to chrysotile. These findings indicate that cell magnetometry detects impaired cytoskeletal function due to in vitro exposure to chrysotile. PMID:10223613

  19. Transpleural Ventilation via Spiracles in Severe Emphysema Increases Alveolar Ventilation.

    PubMed

    Chahla, Mayy; Larson, Christopher D; Parekh, Kalpaj R; Reed, Robert M; Terry, Peter; Schmidt, Gregory A; Eberlein, Michael

    2016-06-01

    In emphysema airway resistance can exceed collateral airflow resistance, causing air to flow preferentially through collateral pathways. In severe emphysema ventilation through openings directly through the chest wall into the parenchyma (spiracles) could bypass airway obstruction and increase alveolar ventilation via transpleural expiration. During lung transplant operations, spiracles occasionally can occur inadvertently. We observed transpleural expiration via spiracles in three subjects undergoing lung transplant for emphysema. During transpleural spiracle ventilation, inspiratory tidal volumes (TV) were unchanged; however, expiration was entirely transpleural in two patients whereas the expired TV to the ventilator circuit was reduced to 25% of the inspired TV in one. At baseline, mean PCO2 was 61 ± 5 mm Hg, which decreased to a mean PCO2 of 49 ± 5 mm Hg (P = .05) within minutes after transpleural spiracle ventilation and further decreased at 1 to 2 h (36 ± 4 mm Hg; P = .002 compared with baseline) on unchanged ventilator settings. This observation of increased alveolar ventilation supports further studies of spiracles as a possible therapy for advanced emphysema. PMID:27287591

  20. Pulmonary alveolar proteinosis. Clinical manifestations and optimal treatment strategies.

    PubMed

    Venkateshiah, Saiprakash B; Thomassen, Mary Jane; Kavuru, Mani S

    2004-01-01

    Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant phospholipids and proteins within the lung alveoli. Important advances have been made over the past 8 years in our understanding of this disease, offering new directions for research and patient care. First, genetically altered mice that are homozygous for a disrupted granulocyte-macrophage colony-stimulating factor (GM-CSF) gene developed a lung lesion with histologic resemblance to PAP. The surfactant is thought to be catabolized or cleared mostly by alveolar macrophages, this process being dependent on GM-CSF. Second, a neutralizing autoantibody against GM-CSF was found in serum and bronchoalveolar lavage fluid of patients with idiopathic PAP but not in healthy controls, thereby raising the suspicion that human PAP may be an autoimmune disease. The relationship between the antibody and disease pathogenesis remains unclear but data suggest that the GM-CSF antibody may have a potential role as a diagnostic test. No specific therapy exists for PAP. Sequential whole lung lavage is the standard of care. Exogenous therapy with GM-CSF may improve the lung disease in some patients with PAP but this therapy is still experimental. Interventions directed at treating a relative GM-CSF deficiency by administration of GM-CSF or lowering the antibody level (i.e. by plasmapheresis or immunosuppression) may hold promise as future therapy for this rare disease. PMID:15350160

  1. Role of alveolar macrophage lysosomes in metal detoxification.

    PubMed

    Berry, J P; Zhang, L; Galle, P; Ansoborlo, E; Hengé-Napoli, M H; Donnadieu-Claraz, M

    1997-02-15

    The intracellular behaviour of different toxic mineral elements inhaled as soluble aerosols or as insoluble particles was studied in the rat by electron microscopy, electron probe microanalysis, and electron microdiffraction. This study showed that, after inhalation, aerosols of soluble elements like cerous chloride, chromic chloride, uranyl nitrate, and aluminium chloride, are concentrated in the lysosomes of alveolar macrophages and are precipitated in the lysosomes in the form of insoluble phosphate, probably due to the activity of acid phosphatase (intralysosomial enzyme). Also, after inhalation of crystalline particles that are insoluble or poorly soluble in water such as the illites (phyllosilicates), ceric oxides (opaline), and industrial uranium oxides (U3O8), the small crystals are captured by the alveolar macrophage lysosomes and transformed over time into an amorphous form. This structural transformation is associated with changes in the chemical nature of particles inhaled in the oxide form. Microanalysis of amorphous deposits observed after inhalation of uranium or ceric oxides has shown that they contain high concentrations of phosphorus associated with the initial elements cerium and uranium. These different processes tend to limit the diffusion of these toxic elements within the organism, whether they are inhaled in soluble form or not. PMID:9140931

  2. Peptide secreted by human alveolar macrophages releases neutrophil granule contents

    SciTech Connect

    MacArthur, C.K.; Miller, E.J.; Cohen, A.B.

    1987-11-15

    A monoclonal antibody was developed against an 8000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose, and by autoradiography. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-..gamma.., tumor necrosis factor, or interleukin l..cap alpha.. or 1..beta... The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes.

  3. Porous calcium phosphate cement for alveolar bone regeneration.

    PubMed

    Félix Lanao, R P; Hoekstra, J W M; Wolke, J G C; Leeuwenburgh, S C G; Plachokova, A S; Boerman, O C; van den Beucken, J J J P; Jansen, J A

    2014-06-01

    The present study aimed to provide information on material degradation and subsequent alveolar bone formation, using composites consisting of calcium phosphate cement (CPC) and poly(lactic-co-glycolic) acid (PLGA) with different microsphere morphology (hollow vs dense). In addition to the plain CPC-PLGA composites, loading the microspheres with the growth factors platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) was investigated. A total of four different CPC composites were applied into one-wall mandible bone defects in beagle dogs in order to evaluate them as candidates for alveolar bone regeneration. These composites consisted of CPC and hollow or dense PLGA microspheres, with or without the addition of PDGF-IGF growth factor combination (CPC-hPLGA, CPC-dPLGA, CPC-hPLGAGF , CPC-dPLGAGF ). Histological evaluation revealed significantly more bone formation in CPC-dPLGA than in CPC-hPLGA composites. The combination PDGF-IGF enhanced bone formation in CPC-hPLGA materials, but significantly more bone formation occurred when CPC-dPLGA was used, with or without the addition of growth factors. The findings demonstrated that CPC-dPLGA composite was the biologically superior material for use as an off-the-shelf material, due to its good biocompatibility, enhanced degradability and superior bone formation. PMID:22777771

  4. Microtomography of the human tooth-alveolar bone complex

    NASA Astrophysics Data System (ADS)

    Dalstra, Michel; Cattaneo, Paolo M.; Beckmann, Felix; Sakima, Maurício T.; Lemor, Carsten; Laursen, Morten G.; Melsen, Birte

    2006-08-01

    In this study the structure of the adult human dentoalveolar process is examined using conventional and synchrotron radiation-based microtomography (SRμCT). Mandibular and maxillary segments containing two to five adjacent teeth were harvested at autopsy from 49 adult donors. These segments were embedded in blocks of methylmetacrylate and scanned using a conventional table-top μCT-scanner at a pixel size and slice thickness of 35 μm. A few segments were also scanned at a synchrotron facility at an initial pixel size of 16.4 μm, which was binned by a factor 2 to result in an effective voxel size of almost 32.8 μm. The three-dimensional reconstructions revealed how intricately the teeth are supported by the alveolar bone. Furthermore, this support is highly inhomogeneous with respect to the buccal, mesial, lingual and distal quadrants. Reflecting their various degrees of mineralization, tissues like bone, dentine, enamel and cementum, could well be identified, especially in the scans made with SRμCT. Despite comparable voxel sizes, the reconstructed data-sets obtained with conventional μCT were less detailed and somewhat fuzzy in appearance compared to the data-sets of SRμCT. However, for quantification of macroscopical features like the thickness of the alveolar wall or the presence of dehiscences/fenestrations this seemed sufficient.

  5. Alveolar recruitment maneuvers: are your patients missing out?

    PubMed

    Hartland, Benjamin L; Newell, Timothy J; Damico, Nicole

    2014-08-01

    Awake, spontaneously breathing humans sigh on average 9 to 10 times per hour. The sigh is a normal homeostatic reflex proposed to maintain pulmonary compliance and decrease the formation of atelectasis by recruiting collapsed alveoli. The induction and maintenance of anesthesia with muscle paralysis and a fixed tidal volume abolish the sigh. Without periodic sighs, patients are left susceptible to atelectasis and its negative sequelae. The prevalence of atelectasis has been estimated to be as high as 100% in patients undergoing general anesthesia. A strong correlation between atelectasis and postoperative pulmonary complications has been demonstrated. Postoperative pulmonary complications lengthen hospital stays and increase healthcare costs. Alveolar recruitment maneuvers, which make up one component of open lung ventilation, have been described as vital capacity breaths, double tidal volume breaths, and sigh breaths. These simple maneuvers result in a sustained increase in airway pressure that serves to recruit collapsed alveoli and improve arterial oxygenation. This article examines the literature regarding the application of alveolar recruitment maneuvers in the perioperative setting. The format is a series of clinically oriented questions posed to help the reader translate available evidence into practice. PMID:25167611

  6. Avoiding injury to the inferior alveolar nerve by routine use of intraoperative radiographs during implant placement.

    PubMed

    Burstein, Jeffrey; Mastin, Chris; Le, Bach

    2008-01-01

    Injury to the inferior alveolar nerve during implant placement in the posterior atrophic mandible is a rare but serious complication. Although a preoperative computerized tomography scan can help determine the distance from the alveolar ridge to the nerve canal, variables such as magnification errors, ridge anatomy, and operator technique can increase the chance for complications. The routine use of intraoperative periapical radiographs during the drilling sequence is an inexpensive and reliable tool, allowing the operator to confidently adjust the direction and depth of the implant during placement. Most important, it helps avoid the risk of injury to the inferior alveolar nerve in cases in which there is limited vertical alveolar bone. Using this technique for 21 implants placed in the posterior atrophic mandible, with less than 10 mm of vertical bone to the inferior alveolar nerve canal, the authors observed no incidents of postoperative paresthesia. PMID:18390241

  7. Alveolar Subphase pH in the Lungs of Anesthetized Rabbits

    NASA Astrophysics Data System (ADS)

    Nielson, D. W.; Goerke, J.; Clements, J. A.

    1981-11-01

    We measured the pH of the alveolar subphase fluid by puncturing the most superficial alveoli of the exposed lungs of anesthetized rabbits with H+-selective and nonselective KCl microelectrodes. In these experiments, we bathed the lung surface with paraffin oil or buffered Ringer's solutions that had a CO2 tension of 40 Torr (1 Torr = 133.3 Pa) and found an alveolar pH of 6.92± 0.01 (mean ± SEM). When the pH of the surface buffer was below 6.7 or above 7.5, alveolar pH varied with surface buffer pH. With the nonselective electrode, we did not find a significant electrical potential difference between the alveolar fluid and the pleural surface. These results are consistent with active transport of H+ (or HCO3-) across alveolar epithelium.

  8. Imaging of the three-dimensional alveolar structure and the alveolar mechanics of a ventilated and perfused isolated rabbit lung with Fourier domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Popp, Alexander; Wendel, Martina; Knels, Lilla; Koch, T.; Koch, Edmund

    2006-01-01

    In this feasibility study, Fourier domain optical coherence tomography (FDOCT) is used for visualizing the 3-D structure of fixated lung parenchyma and to capture real-time cross sectional images of the subpleural alveolar mechanics in a ventilated and perfused isolated rabbit lung. The compact and modular setup of the FDOCT system allows us to image the first 500 µm of subpleural lung parenchyma with a 3-D resolution of 16×16×8 µm (in air). During mechanical ventilation, real-time cross sectional FDOCT images visualize the inflation and deflation of alveoli and alveolar sacks (acini) in successive images of end-inspiratory and end-expiratory phase. The FDOCT imaging shows the relation of local alveolar mechanics to the setting of tidal volume (VT), peak airway pressure, and positive end-expiratory pressure (PEEP). Application of PEEP leads to persistent recruitment of alveoli and acini in the end-expiratory phase, compared to ventilation without PEEP where alveolar collapse and reinflation are observed. The imaging of alveolar mechanics by FDOCT will help to determine the amount of mechanical stress put on the alveolar walls during tidal ventilation, which is a key factor in understanding the development of ventilator induced lung injury (VILI).

  9. Imaging of the three-dimensional alveolar structure and the alveolar mechanics of a ventilated and perfused isolated rabbit lung with Fourier domain optical coherence tomography.

    PubMed

    Popp, Alexander; Wendel, Martina; Knels, Lilla; Koch, Thea; Koch, Edmund

    2006-01-01

    In this feasibility study, Fourier domain optical coherence tomography (FDOCT) is used for visualizing the 3-D structure of fixated lung parenchyma and to capture real-time cross sectional images of the subpleural alveolar mechanics in a ventilated and perfused isolated rabbit lung. The compact and modular setup of the FDOCT system allows us to image the first 500 microm of subpleural lung parenchyma with a 3-D resolution of 16 x 16 x 8 microm (in air). During mechanical ventilation, real-time cross sectional FDOCT images visualize the inflation and deflation of alveoli and alveolar sacks (acini) in successive images of end-inspiratory and end-expiratory phase. The FDOCT imaging shows the relation of local alveolar mechanics to the setting of tidal volume (VT), peak airway pressure, and positive end-expiratory pressure (PEEP). Application of PEEP leads to persistent recruitment of alveoli and acini in the end-expiratory phase, compared to ventilation without PEEP where alveolar collapse and reinflation are observed. The imaging of alveolar mechanics by FDOCT will help to determine the amount of mechanical stress put on the alveolar walls during tidal ventilation, which is a key factor in understanding the development of ventilator induced lung injury (VILI). PMID:16526892

  10. Local abnormalities of coagulation and fibrinolytic pathways that promote alveolar fibrin deposition in the lungs of baboons with diffuse alveolar damage.

    PubMed Central

    Idell, S; Peters, J; James, K K; Fair, D S; Coalson, J J

    1989-01-01

    Because alveolar fibrin is a prominent histologic feature of diffuse lung injury in baboons, we hypothesized that local abnormalities of pathways of fibrin turnover would favor fibrin deposition in the alveolar space. To test this hypothesis, procoagulant and fibrinolytic activities were characterized in serial bronchoalveolar lavage (BAL) of baboons with evolving diffuse alveolar damage (DAD) induced by exposure to 100% O2. BAL procoagulant activity, characterized mainly as the tissue factor-Factor VII complex, was markedly increased after induction of DAD. Extrinsic pathway inhibitor was likewise increased in BAL during evolving DAD but was insufficient to control coagulation. Urokinase-like fibrinolytic activity was usually detectable in baseline BAL but was undetectable after 7 d of O2. DAD BAL contained significantly increased plasminogen levels, plasmin inhibitor activity sufficient to neutralize all plasmin produced by BAL plasminogen activator found in control BAL and detectable plasminogen activator inhibitor-1. Antiplasmin activity was due, in part, to increased alpha 2-antiplasmin. These changes correlated with quantitatively increased alveolar fibrin deposition demonstrated by histologic and morphometric analyses. Multiple abnormalities of pathways of fibrin turnover occur concurrently in the alveolar compartment of the lungs of baboons with DAD, which collectively predispose to diffuse alveolar fibrin deposition. Images PMID:2738151

  11. Presurgical orthodontic decompensation alters alveolar bone condition around mandibular incisors in adults with skeletal Class III malocclusion

    PubMed Central

    Sun, Boyang; Tang, Jun; Xiao, Ping; Ding, Ying

    2015-01-01

    This study is to use cone beam computed tomography (CBCT) to acquire accurate radiographic images for alveolar bone in lower incisors and the change after presurgical orthodontic treatment. Seventeen patients with skeletal Class III malocclusion, ten normal occlusion subjects, and fifteen patients treated with orthodontic treatment and orthognathic surgery were included. CBCT images were obtained. The labial and lingual inclinations of mandibular incisors, the thickness of alveolar bone, the vertical alveolar height and root length were measured. Alveolar bone thickness at the apex in patients with skeletal Class III malocclusion was thinner than normal subjects. The vertical alveolar bone heights at labial and lingual sides in patients with skeletal Class III malocclusion were both reduced compared with normal subjects, especially at the labial side. There were statistically significant correlations between lower incisor inclination and alveolar bone morphology. After orthodontics, the incisors root apex was closer to the lingual side of alveolar bone. The alveolar bone thickness at apex was not statistically changed. The vertical alveolar bone heights at the labial and lingual sides were both significantly reduced especially the lingual side after presurgical orthodontic treatment. The root length was not significantly changed. In conclusion, the alveolar bone thickness at apex is thinner and the vertical alveolar height is reduced at the labial side. Forward movement of lower incisors during presurgical orthodontic treatment can render the lower incisors root apex closer to the lingual side and the vertical alveolar height is reduced. PMID:26550202

  12. Inhibition of immunological function mediated DNA damage of alveolar macrophages caused by cigarette smoke in mice.

    PubMed

    Ishida, Takahiro; Hirono, Yuriko; Yoshikawa, Kenichi; Hutei, Yoshimi; Miyagawa, Mayuko; Sakaguchi, Ikuyo; Pinkerton, Kent E; Takeuchi, Minoru

    2009-12-01

    Exposure to cigarette smoke impairs the pulmonary immune system, including alveolar macrophage function, although the mechanisms by which this occurs are not fully elucidated. This study investigates the effect of cigarette smoke exposure on the antigen-presenting activity of alveolar macrophages, which is required for antigen-specific response to T cells. C57BL/6 mice were exposed to cigarette smoke for 10 days using a Hamburg II smoking machine, and alveolar macrophages were obtained by bronchoalveolar lavage. The antigen-presenting activity of alveolar macrophages was significantly inhibited in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. Major histocompatibility complex class II cell surface molecule-positive cells, B7-1 molecule-positive cells, and interleukin-1beta messenger RNA gene expression in alveolar macrophages were significantly decreased in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. In contrast, DNA damage and generation of superoxide and hydrogen peroxide in alveolar macrophages were significantly increased by cigarette smoke exposure. These results suggest that inhibition of the antigen-presenting activity of alveolar macrophages may result from decreased expression of major histocompatibility complex class II and B7-1 molecules and interleukin-1beta messenger RNA gene expression following cigarette smoke exposure. Furthermore, inhibition of antigen presentation in alveolar macrophage may result from DNA damage induced by excessive amounts of reactive oxygen species being generated by alveolar macrophages following cigarette smoke exposure. These findings suggest that cigarette smoke impairs the immunological function of alveolar macrophages and, as a result, increases the risk for pulmonary infection. PMID:19922407

  13. Rate and extent of leakage of a magnetic resonance contrast agent tend to be lower under isoflurane anesthesia in comparison to halothane in a rat model of embolic stroke.

    PubMed

    Bezerra, Francisco J; Brown, Morris; Alarcon, William; Karki, Kishor; Knight, Robert A; Keenan, Kelly A; Nagaraja, Tavarekere N

    2014-09-01

    Cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability by arterial spin labeling (ASL)- and dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI), respectively were repeatedly measured under either halothane (N  =  5) or isoflurane (N  =  5) anesthesia in a rat stroke model of embolic occlusion of middle cerebral artery (MCA). Cerebral blood flow measurements were made after MCA embolization, following intravenous recombinant tissue plasminogen activator (rtPA) treatment at 3 hours post-ictus and again at 48 hours. Blood-brain barrier opening was examined after rtPA infusion and again at 48 hours. Data were analyzed using paired t-tests and significance considered at P < 0·05. The extent and magnitude of CBF reduction due to stroke did not differ between the two groups. Blood-to-brain forward rate constant, K(trans), a measure of BBB permeability, for an MRI contrast agent gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), was elevated in the ipsilateral hemisphere in both cohorts. However, isoflurane-anesthetized rats exhibited a trend of lower K(trans) values at 48 hours (P  =  0·06) indicating reduced BBB damage in the ipsilateral hemisphere. The area of BBB opening followed a similar trend with the isoflurane-anesthetized group exhibiting a smaller area of BBB damage acutely and at 48 hours compared to the halothane-anesthetized group. PMID:24601723

  14. VEGF and endothelium-derived retinoic acid regulate lung vascular and alveolar development.

    PubMed

    Yun, Eun Jun; Lorizio, Walter; Seedorf, Gregory; Abman, Steven H; Vu, Thiennu H

    2016-02-15

    Prevention or treatment of lung diseases caused by the failure to form, or destruction of, existing alveoli, as observed in infants with bronchopulmonary dysplasia and adults with emphysema, requires understanding of the molecular mechanisms of alveolar development. In addition to its critical role in gas exchange, the pulmonary circulation also contributes to alveolar morphogenesis and maintenance by the production of paracrine factors, termed "angiocrines," that impact the development of surrounding tissue. To identify lung angiocrines that contribute to alveolar formation, we disrupted pulmonary vascular development by conditional inactivation of the Vegf-A gene during alveologenesis. This resulted in decreased pulmonary capillary and alveolar development and altered lung elastin and retinoic acid (RA) expression. We determined that RA is produced by pulmonary endothelial cells and regulates pulmonary angiogenesis and elastin synthesis by induction of VEGF-A and fibroblast growth factor (FGF)-18, respectively. Inhibition of RA synthesis in newborn mice decreased FGF-18 and elastin expression and impaired alveolarization. Treatment with RA and vitamin A partially reversed the impaired vascular and alveolar development induced by VEGF inhibition. Thus we identified RA as a lung angiocrine that regulates alveolarization through autocrine regulation of endothelial development and paracrine regulation of elastin synthesis via induction of FGF-18 in mesenchymal cells. PMID:26566904

  15. Depletion of resident alveolar macrophages does not prevent Fas-mediated lung injury in mice.

    PubMed

    Bem, R A; Farnand, A W; Wong, V; Koski, A; Rosenfeld, M E; van Rooijen, N; Frevert, C W; Martin, T R; Matute-Bello, G

    2008-08-01

    Activation of the Fas/Fas ligand (FasL) system in the lungs results in a form of injury characterized by alveolar epithelial apoptosis and neutrophilic inflammation. Studies in vitro show that Fas activation induces apoptosis in alveolar epithelial cells and cytokine production in alveolar macrophages. The main goal of this study was to determine the contribution of alveolar macrophages to Fas-induced lung inflammation in mice, by depleting alveolar macrophages using clodronate-containing liposomes. Liposomes containing clodronate or PBS were instilled by intratracheal instillation. After 24 h, the mice received intratracheal instillations of the Fas-activating monoclonal antibody Jo2 or an isotype control antibody and were studied 18 h later. The Jo2 MAb induced increases in bronchoalveolar lavage fluid (BALF) total neutrophils, lung caspase-3 activity, and BALF total protein and worsened histological lung injury in the macrophage-depleted mice. Studies in vitro showed that Fas activation induced the release of the cytokine KC in a mouse lung epithelial cell line, ML