Histamine release after intravenous application of short-acting hypnotics. A comparison of etomidate, Althesin (CT1341) and propanidid

The subject of histamine release was investigated in 16 volunteers by means of plasma histamine determination after the administration of etornidate, Althesin, propanidid, and Cremophor EL. Althesin and propanidid caused release of histamine in various degrees of frequency. Blood pressure changes were rather pronounced with both anaesthetic agents; tachycardia reached its maximum in the first and second minute, which seems to be an argument against histamine release as the underlying cause of this reaction. Histamine was, indeed, only released to such an extent (with the exception of one borderline case) that no clinical symptoms other than secretion of gastric juice and erythema were to be expected. After the application of etomidate and Cremophor EL an increase in plasma histamine was not detectable. Changes in the differential blood picture in terms of a decrease in basophils only occurred after Althesin and propanidid; not, however, after etomidate and Cremophor EL. Etomidate is, therefore, the first hypnotic drug for intravenous application which is unlikely to cause chemical histamine release

Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 (G93A) Mice

Heterogeneity of glia in different CNS regions may contribute to the selective vulnerability of neuronal populations in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS). Here, we explored regional variations in the expression of heat shock protein 25 in glia under conditions of acute and chronic stress. Hsp27 (Hsp27; murine orthologue: Hsp25) fulfils a number of cytoprotective functions and may therefore be a possible therapeutic target in ALS. We identified a subpopulation of astrocytes in primary murine mixed glial cultures that expressed Hsp25. Under basal conditions, the proportion of Hsp25-positive astrocytes was twice as high in spinal cord cultures than in cortical cultures. To explore the physiological role of the elevated Hsp25 expression in spinal cord astrocytes, we exposed cortical and spinal cord glia to acute stress, using heat stress and pro-inflammatory stimuli. Surprisingly, we observed no stress-induced increase in Hsp25 expression in either cortical or spinal cord astrocytes. Similarly, exposure to endogenous stress, as modelled in glial cultures from SOD1 G93A-ALS mice, did not increase Hsp25 expression above that observed in astrocytes from wild-type mice. In vivo, Hsp25 expression was greater under conditions of chronic stress present in the spinal cord of SOD1 G93A mice than in wild-type mice, although this increase in expression is likely to be due to the extensive gliosis that occurs in this model. Together, these results show that there are differences in the expression of Hsp25 in astrocytes in different regions of the central nervous system, but Hsp25 expression is not upregulated under acute or chronic stress conditions

Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing

Aprataxin (APTX) deficiency causes progressive cerebellar degeneration, ataxia and oculomotor apraxia in man. Cell free assays and crystal structure studies demonstrate a role for APTX in resolving 5'-adenylated nucleic acid breaks, however, APTX function in vertebrates remains unclear due to the lack of an appropriate model system. Here, we generated a murine model in which a pathogenic mutant of superoxide dismutase 1 (SOD1(G93A)) is expressed in an Aptx-/- mouse strain. We report a delayed population doubling and accelerated senescence in Aptx-/- primary mouse fibroblasts, which is not due to detectable telomere instability or cell cycle deregulation but is associated with a reduction in transcription recovery following oxidative stress. Expression of SOD1(G93A) uncovers a survival defect ex vivo in cultured cells and in vivo in tissues lacking Aptx. The surviving neurons feature numerous and deep nuclear envelope invaginations, a hallmark of cellular stress. Furthermore, they possess an elevated number of high-density nuclear regions and a concomitant increase in histone H3 K9 trimethylation, hallmarks of silenced chromatin. Finally, the accelerated cellular senescence was also observed at the organismal level as shown by down-regulation of insulin-like growth factor 1 (IGF-1), a hallmark of premature ageing. Together, this study demonstrates a protective role of Aptx in vivo and suggests that its loss results in progressive accumulation of DNA breaks in the nervous system, triggering hallmarks of premature ageing, systemically

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia:a study in rats

In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9-11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage

Sintesis Mg2+ Doped ZnO dengan Penambahan Albumen Ayam Ras Menggunakan Gabungan Metode Sol-Gel dan Sonokimia

Mg2+ doped ZnO has been successfully synthesized using a combination of sol-gel and sonochemical methods. Zinc acetate dihydrate was used as a precursor, magnesium chloride hexahydrate as a source of Mg dopant, methanol as a solvent, and chicken albumen was used as an additive to replace monoethanolamine. The sol was heated at 110 °C for 1 hour. The gel formed was calcined at 600 °C for 3 hours. FTIR analysis shows that the absorbance band around 400-450 cm-1 indicates Mg-O stretching, the absorbance band around 500-550 cm-1 indicates Zn-O stretching, the absorbance band around 400-550 cm-1 shows Zn-O-Mg bonds. Mg. Measurements with UV-DRS, obtained the smallest ZnO band gap value doped Mg2+ around 2.7 eV with the addition of 10 mL albumen. The resulting crystal structure was wurtzite with crystal size with the addition of 10, 20, 30, 40 and 50 mL albumen were 25.22-55.91 nm, 32.99-75.87 nm, 45.92-83.91 nm, 45.92-75.89 nm and 46.15-71.47 nm respectively. SEM photo of Mg2+ doped ZnO with the addition of 10 mL of albumen has a hexagonal surface morphology

Improved haemodynamic stability and cerebral tissue oxygenation after induction of anaesthesia with sufentanil compared to remifentanil : a randomised controlled trial

Background: Balanced anaesthesia with propofol and remifentanil, compared to sufentanil, often decreases mean arterial pressure (MAP), heart rate (HR) and cardiac index (CI), raising concerns on tissue-oxygenation. This distinct haemodynamic suppression might be attenuated by atropine. This double blinded RCT, investigates if induction with propofol-sufentanil results in higher CI and tissue-oxygenation than with propofol-remifentanil and if atropine has more pronounced beneficial effects on CI and tissue-oxygenation in a remifentanil-based anaesthesia. Methods: In seventy patients scheduled for coronary bypass grafting (CABG), anaesthesia was induced and maintained with propofol target controlled infusion (TCI) with a target effect-site concentration (Cet) of 2.0 mu g ml(- 1)and either sufentanil (TCI Cet 0.48 ng ml(- 1)) or remifentanil (TCI Cet 8 ng ml(- 1)). If HR dropped below 60 bpm, methylatropine (1 mg) was administered intravenously. Relative changes (increment ) in MAP, HR, stroke volume (SV), CI and cerebral (SctO(2)) and peripheral (SptO(2)) tissue-oxygenation during induction of anaesthesia and after atropine administration were analysed. Results: The sufentanil group compared to the remifentanil group showed significantly less decrease in MAP (increment = - 23 +/- 13 vs. -36 +/- 13 mmHg), HR (increment = - 5 +/- 7 vs. -10 +/- 10 bpm), SV (increment = - 23 +/- 18 vs. -35 +/- 19 ml) and CI (increment = - 0.8 (- 1.5 to - 0.5) vs. -1.5 (- 2.0 to - 1.1) l min(- 1) m(- 2)), while SctO(2) (increment = 9 +/- 5 vs. 6 +/- 4%) showed more increase with no difference in increment SptO(2) (increment = 8 +/- 7 vs. 8 +/- 8%). Atropine caused higher increment HR (13 (9 to 19) vs. 10 +/- 6 bpm) and increment CI (0.4 +/- 0.4 vs. 0.2 +/- 0.3 l min(- 1) m(- 2)) in sufentanil vs. remifentanil-based anaesthesia, with no difference in increment MAP, increment SV and increment SctO(2) and increment SptO(2). Conclusion: Induction of anaesthesia with propofol and sufentanil results in improved haemodynamic stability and higher SctO(2) compared to propofol and remifentanil in patients having CABG. Administration of atropine might be useful to counteract or prevent the haemodynamic suppression associated with these opioids

A quantitative and qualitative comparison of fibrin glue, albumin, and blood as agents to pretreat porous vascular grafts

Recent reports suggest that fibrin glue can be used to seal porous vascular grafts prior to insertion, but this ability has not been quantitatively compared to existing methods. We compared blood loss from and handling characteristics of grafts pretreated with either fibrin glue (FG) (Tisseel), albumin autoclaving (AA), or blood preclotting (BP). Five 6-cm segments of 6-mm internal diameter grafts, both knitted and woven double velour Dacron were treated in each group (30 specimens). Human blood was forced through the BP group until clotted; AA segments were soaked in 25% human albumin and autoclaved for 10 min; FG segments were treated with a topical application of Tisseel (0.5 ml/graft) followed by treatment with topical thrombin + CACl (0.5 ml/graft). Graft ends were sealed and attached to a transducer/syringe pump mechanism which pumped heparinized human blood into the graft at 100 mm Hg intraluminal pressure. All blood that leaked through the grafts over 2 min was collected and the amount was averaged for the five grafts in each group. Graft handling was characterized as either pliable or stiff. Blood pretreatment caused 21 +/- 2 and 13 +/- 4 cc/2 min of leak in knitted and woven grafts, respectively. Albumin autoclaving resulted in 9 +/- 2 and 1 +/- 0.5 cc of leak (P P < 0.01 compared to blood). Both blood and fibrin glue produced soft pliable grafts, while albumin pretreatment resulted in stiff grafts. We conclude that fibrin glue or albumin is superior to blood for pretreatment of woven grafts in limiting blood loss, but that fibrin glue is superior to either albumin or blood in knitted grafts. Fibrin glue imparts superior handling characteristics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26651/1/0000195.pd

Astrocytes display cell autonomous and diverse early reactive states in familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a rapidly progressive and fatal disease. Although astrocytes are increasingly recognized contributors to the underlying pathogenesis, the cellular autonomy and uniformity of astrocyte reactive transformation in different genetic forms of amyotrophic lateral sclerosis remain unresolved. Here we systematically examine these issues by using highly enriched and human induced pluripotent stem cell-derived astrocytes from patients with VCP and SOD1 mutations. We show that VCP mutant astrocytes undergo cell-autonomous reactive transformation characterized by increased expression of complement component 3 (C3) in addition to several characteristic gene expression changes. We then demonstrate that isochronic SOD1 mutant astrocytes also undergo a cell-autonomous reactive transformation, but that this is molecularly distinct from VCP mutant astrocytes. This is shown through transcriptome-wide analyses, identifying divergent gene expression profiles and activation of different key transcription factors in SOD1 and VCP mutant human induced pluripotent stem cell-derived astrocytes. Finally, we show functional differences in the basal cytokine secretome between VCP and SOD1 mutant human induced pluripotent stem cell-derived astrocytes. Our data therefore reveal that reactive transformation can occur cell autonomously in human amyotrophic lateral sclerosis astrocytes and with a striking degree of early molecular and functional heterogeneity when comparing different disease-causing mutations. These insights may be important when considering astrocyte reactivity as a putative therapeutic target in familial amyotrophic lateral sclerosis