Things you wanted to know (but might have been afraid to ask) about how and why to explore and modulate brain plasticity with non-invasive neurostimulation technologies.

Brain plasticity can be defined as the ability of local and extended neural systems to organize either the structure and/or the function of their connectivity patterns to better adapt to changes of our inner/outer environment and optimally respond to new challenging behavioral demands. Plasticity has been traditionally conceived as a spontaneous phenomenon naturally occurring during pre and postnatal development, tied to learning and memory processes, or enabled following neural damage and their rehabilitation. Such effects can be easily observed and measured but remain hard to harness or to tame 'at will'. Non-invasive brain stimulation (NIBS) technologies offer the possibility to engage plastic phenomena, and use this ability to characterize the relationship between brain regions, networks and their functional connectivity patterns with cognitive process or disease symptoms, to estimate cortical malleability, and ultimately contribute to neuropsychiatric therapy and rehabilitation. NIBS technologies are unique tools in the field of fundamental and clinical research in humans. Nonetheless, their abilities (and also limitations) remain rather unknown and in the hands of a small community of experts, compared to widely established methods such as functional neuroimaging (fMRI) or electrophysiology (EEG, MEG). In the current review, we first introduce the features, mechanisms of action and operational principles of the two most widely used NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Current Stimulation (tCS), for exploratory or therapeutic purposes, emphasizing their bearings on neural plasticity mechanisms. In a second step, we walk the reader through two examples of recent domains explored by our team to further emphasize the potential and limitations of NIBS to either explore or improve brain function in healthy individuals and neuropsychiatric populations. A final outlook will identify a series of future topics of interest that can foster progress in the field and achieve more effective manipulation of brain plasticity and interventions to explore and improve cognition and treat the symptoms of neuropsychiatric diseases.

In vivo and in vitro properties of STX2484: a novel non-steroidal anti-cancer compound active in taxane-resistant breast cancer.

BACKGROUND: STX2484 is a novel non-steroidal compound with potent anti-proliferative activity. These studies aimed to identify STX2484's mechanism of action, in vivo efficacy and activity in taxane-resistant breast cancer models. METHODS: Effects of STX2484 and paclitaxel on proliferation, cell cycle and apoptosis were assessed in vitro in drug-resistant (MCF-7(DOX)) and non-resistant cells (MCF-7(WT)). STX2484 efficacy in ßIII tubulin overexpression in MCF-7 cells was also determined. Anti-angiogenic activity was quantified in vitro by a co-culture model and in vivo using a Matrigel plug assay. An MDA-MB-231 xenograft model was used to determine STX2484 efficacy in vivo. RESULTS: STX2484 is a tubulin disruptor, which induces p53 expression, Bcl2 phosphorylation, caspase-3 cleavage, cell cycle arrest and apoptosis. In addition, STX2484 is a potent anti-angiogenic agent in vitro and in vivo. In breast cancer xenografts, STX2484 (20 mg kg(-1) p.o.) suppressed tumour growth by 84% after 35 days of daily dosing, with limited toxicity. In contrast to paclitaxel, STX2484 efficacy was unchanged in two clinically relevant drug-resistant models. CONCLUSIONS: STX2484 is an orally bioavailable microtubule-disrupting agent with in vivo anti-angiogenic activity and excellent in vivo efficacy with no apparent toxicity. Crucially, STX2484 has superior efficacy to paclitaxel in models of clinical drug resistance.

Dietary hyperthyroidism in dogs.

OBJECTIVES: Evaluation of dogs with elevated plasma thyroxine concentration fed raw food before and after changing the diet. METHOD: Between 2006 and 2011 all dogs presented with an elevated plasma thyroxine concentration and a dietary history of feeding raw food were included. Thyroxine (reference interval: 19·3 to 51·5 nmol/L) and in many cases also thyroid-stimulating hormone concentrations (reference interval: <0·30 ng/mL) were measured initially and after changing the diet. RESULTS: Twelve dogs were presented with a median age of five years. The median plasma thyroxine concentration was 156·1 (range of 79·7 to 391·9) nmol/L; in six dogs, thyroid-stimulating hormone concentration was measured and was <0·03 ng/mL in five dogs and 0·05 ng/mL in one dog. Six dogs showed clinical signs such as weight loss, aggressiveness, tachycardia, panting and restlessness while six dogs had no clinical signs. After changing the diet eight dogs were examined: thyroxine concentration normalised in all dogs and clinical signs resolved. CLINICAL SIGNIFICANCE: Dietary hyperthyroidism can be seen in dogs on a raw meat diet or fed fresh or dried gullets. Increased plasma thyroxine concentration in a dog, either with or without signs of hyperthyroidism, should prompt the veterinarian to obtain a thorough dietary history.

Inhibition of cell cycle progression by dual phosphatidylinositol-3-kinase and mTOR blockade in cyclin D2 positive multiple myeloma bearing IgH translocations.

Multiple myeloma (MM) is a clinically and genetically heterogenous cancer where tumour cells have dysregulated expression of a D-type cyclin, often in association with a recurrent IgH translocation. Patients whose tumour cells express cyclin D2, with the translocation t(4;14) or t(14;16), generally have more proliferative disease and inferior outcomes. The phosphatidylinositol-3-kinase (PI3K) pathway is a major regulator of D-type cyclin expression and cell cycle entry. We evaluated the effect of PI3K pathway blockade on cell cycle behaviour in MM cells, investigating differences between cyclin D2- and cyclin D1-expressing tumours. MM cell lines and primary bone marrow CD138(+) MM cells were exposed to the pan-PI3K/mTOR inhibitor, PI-103, and assessed for cell cycle profiles, [(3)H]-thymidine uptake and cell cycle proteins. We report, in both cell lines and primary MM cells, that PI-103 induced cell cycle arrest with downregulation of cyclin D2 and CDK4/6 in MM cells expressing cyclin D2 via t(4;14) or t(14;16) translocations. Cells expressing cyclin D1 via t(11;14) were insensitive to PI-103, despite exhibiting inhibition of downstream signalling targets. In primary MM cells, PI-103 enhanced the anti-proliferative effects of anti-MM agents. Treatment paradigms including blockade of the PI3K/mTOR pathway should be targeted at patients with IgH translocations associated with cyclin D2 overexpression.

Efficacy and adverse effects of the antiviral compound plerixafor in feline immunodeficiency virus-infected cats.

BACKGROUND: Bicyclam derivatives inhibit feline immunodeficiency virus (FIV) replication through selective blockage of chemokine receptor CXCR4. HYPOTHESIS/OBJECTIVES: CXCR4 antagonist plerixafor (AMD3100, 1,1'-bis-1,4,8,11-tetraazacyclotetradekan) alone or combination with adefovir (PMEA, 9-(2-phosphonylmethoxyethyl)adenine) safe and effective for treating FIV-infected cats. ANIMALS: Forty naturally FIV-infected, privately owned cats. MATERIALS AND METHODS: Prospective, placebo-controlled, double-blind clinical trial. Cats randomly classified into 4 treatment groups. Received AMD3100, PMEA, AMD3100 in combination with PMEA, or placebo for 6 weeks. Clinical and laboratory parameters, including CD4(+) and CD8(+) cell counts, FIV proviral and viral load measured by quantitative polymerase chain reaction (qPCR) evaluated. Additionally, FIV isolates from cats treated with AMD3100 tested for drug resistance. RESULTS: FIV-infected cats treated with AMD3100 caused significant decrease in proviral load compared to placebo group (2.3 ± 3.8% to 1.9 ± 3.1%, of blood lymphocytes P < .05), but did not lead to improvement of clinical or immunological variables; it caused a decrease in serum magnesium concentration without clinical signs. No development of resistance of FIV isolates to AMD3100 found during treatment period. PMEA administration improved stomatitis (stomatitis score [degree 1 - 100] PMEA group: 23 ± 19 to 11 ± 10, P < .001; AMD3100 + PMEA group: 12 ± 17 to 3 ± 5, P < .05), but did not decrease proviral or viral load and caused anemia (RBC [× 10(6) /µL] PMEA group: 9.07 ± 1.60 to 6.22 ± 2.16, P < .05; AMD3100 ± PMEA group: 8.80 ± 1.23 to 5.84 ± 1.58, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of CXCR4 antagonists, as AMD3100, can induce reduction of proviral load and may represent viable treatment of FIV-infected cats. Combination treatment with PMEA not recommended.

Optimal induction of myeloma cell death requires dual blockade of phosphoinositide 3-kinase and mTOR signalling and is determined by translocation subtype.

Novel inhibitors of PI3K, Akt and mTOR have been developed recently, some of which have entered clinical trials. Although such compounds inhibit cell proliferation, their effects on cell survival, an important determinant of clinical response, are less distinct. Using a broad panel of myeloma cell lines and primary patient samples, we show that dual PI3K and mTOR inhibition can induce cell death. The effects are most marked in cells expressing the t(4;14) translocation, whereas t(11;14) cells are largely resistant. Using specific inhibitors of individual pathway components, we show that optimal induction of cell death requires inhibition of both PI3K and mTOR. This is due to a PI3K-independent component of mTOR activation downstream of the MAP kinase pathway. Novel mTOR kinase inhibitors, which block both TORC1 and TORC2 complexes thereby also reducing Akt activity, are less effective than dual PI3K/mTOR inhibitors because of feedback activation of PI3K signalling. Dual PI3K/mTOR inhibitors sensitise t(4;14) and t(14;16), but not t(11;14), expressing cells to the cytotoxic effects of dexamethasone. We have identified a robust cytogenetic biomarker for response to PI3K/mTOR inhibition--these results will inform the design and prioritisation of clinical studies with novel inhibitors in genetic subgroups of myeloma.

Class III beta-tubulin expression and in vitro resistance to microtubule targeting agents.

BACKGROUND: Class III beta-tubulin overexpression is a marker of resistance to microtubule disruptors in vitro, in vivo and in the clinic for many cancers, including breast cancer. The aims of this study were to develop a new model of class III beta-tubulin expression, avoiding the toxicity associated with chronic overexpression of class III beta-tubulin, and study the efficacy of a panel of clinical and pre-clinical drugs in this model. METHODS: MCF-7 (ER+ve) and MDA-MB-231 (ER-ve) were either transfected with pALTER-TUBB3 or siRNA-tubb3 and 24 h later exposed to test compounds for a further 96 h for proliferation studies. RT-PCR and immunoblotting were used to monitor the changes in class III beta-tubulin mRNA and protein expression. RESULTS: The model allowed for subtle changes in class III beta-tubulin expression to be achieved, which had no direct effect on the viability of the cells. Class III beta-tubulin overexpression conferred resistance to paclitaxel and vinorelbine, whereas downregulation of class III beta-tubulin rendered cells more sensitive to these two drugs. The efficacy of the colchicine-site binding agents, 2-MeOE2, colchicine, STX140, ENMD1198 and STX243 was unaffected by the changes in class III beta-tubulin expression. CONCLUSION: These data indicate that the effect of class III beta-tubulin overexpression may depend on where the drug's binding site is located on the tubulin. Therefore, this study highlights for the first time the potential key role of targeting the colchicine-binding site, to develop new treatment modalities for taxane-refractory breast cancer.

A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140.

UNLABELLED: This study characterises two recently developed anticancer agents in vitro and in vivo, 2-methoxyoestra-1,3,5(10), 16-tetraene-3-carboxamide (IRC-110160) and STX140. MATERIALS AND METHODS: Hormone-dependent (MCF-7), hormone-independent (MDA-MB-231) and P-glycoprotein overexpressing (MCF-7Dox) cells were used for proliferation experiments. For the tumour efficacy studies, female nude mice were inoculated with MDA-MB-231 cells. RESULTS: IRC-110160 is a potent inhibitor of both MCF-7 and MDA-MB-231 cell proliferation. Furthermore, the potency of IRC-110160 was unaffected by the over-expression of the P-glycoprotein drug efflux pump. IRC-110160 and 2-methoxyoestradiol-3,17-O,O-bis-sulfamate (STX140) induced apoptosis in a similar timeframe in the MDA-MB-231 cell line, but only STX140 caused G2/M arrest in these cells. In the MDA-MB-231 xenograft model 300 mg/kg p.o. (daily) of IRC-110160 and 20 mg/kg p.o. STX140 (daily) both completely inhibited tumour growth; however some toxicity was observed with IRC-110160. After 28 days of daily dosing STX140 (20 mg/kg p.o.) had minimal effect on the white blood population of mice with tumours. The masking of STX140 from white blood cells may be due to its interaction with carbonic anhydrase II (CAII) in the red blood cells. In contrast to STX140, IRC-110160 does not inhibit CAII. These studies highlight the activity of two orally bioavailable anti-cancer agents one of which, STX140, may offer a significant clinical advantage over existing drugs as a common dose limiting factor, haemotoxicity, may be minimised.

Canine leptospirosis infections - clinical signs and outcome with different suspected Leptospira serogroups (42 cases).

OBJECTIVES: The aim of the study was to investigate the presence of serum antibodies to different Leptospira serogroups in dogs with a clinical diagnosis of leptospirosis in southern Germany and to compare seroreactivity to different serogroups with history, clinical signs, laboratory findings and survival rate. METHODS: In this study, the data of 42 dogs with the diagnosis of leptospirosis were evaluated retrospectively. Dogs were presented to the Small Animal Medicine Teaching Hospital (Medizinische Kleintierklinik) of the Ludwig Maximilians University Munich, Germany, between 1990 to 2003. RESULTS: Reactivity to the serogroup grippotyphosa (13/42) was most frequently present, followed by reactivity to the serogroup saxkoebing (10/42). There was no difference in the clinical picture and the laboratory changes between dogs whose sera were reactive to different serogroups. CLINICAL SIGNIFICANCE: Most of the dogs with leptospirosis in southern Germany had sera reacting to serogroups other than icterohaemorrhagiae and canicola, which are contained in the vaccine. Thus, currently available vaccines in Europe do not protect against the most common Leptospira organisms associated with clinical disease.

Factors associated with upper respiratory tract disease caused by feline herpesvirus, feline calicivirus, Chlamydophila felis and Bordetella bronchiseptica in cats: experience from 218 European catteries.

A full history of the management practices and the prevalence of upper respiratory tract disease (URTD) at 218 rescue shelters, breeding establishments and private households with five or more cats was recorded. Oropharyngeal and conjunctival swabs and blood samples were taken from 1748 cats. The prevalences of feline herpesvirus (FHV), feline calicivirus (FCV), Chlamydophila felis and Bordetella bronchiseptica were determined by PCR on swab samples. An ELISA was applied to determine the prevalence of antibodies to B. bronchiseptica. The rates of detection by PCR of each pathogen in the cats in catteries with and without ongoing URTD were, respectively, FHV 16 per cent and 8 per cent; FCV 47 per cent and 29 per cent; C. felis 10 per cent and 3 per cent; and B. bronchiseptica 5 per cent and 1.3 per cent; the seroprevalences of B. bronchiseptica were 61 per cent and 41 per cent, respectively. There was evidence that FHV, FCV and B. bronchiseptica played a role in URTD. The risk factors associated with the disease were less than excellent hygiene, contact with dogs with URTD, and larger numbers of cats in the cattery or household.

[A comparative study of analog and digital intraoral x-ray image detector systems]. / Vergleichende Untersuchung analoger und digitaler intraoraler Röntgenbild-Empfängersysteme.

UNLABELLED: The object of this investigation was to compare different intraoral, analog and digital X-ray image detector systems with respect to the diagnostic performance and to the relation of dose and image quality. METHODS: Three different intraoral film types and one digital system were compared. The same basic image quality-related technical parameters were measured, Contrast detail diagrams and images of pig teeth were captured and evaluated by visual inspection. RESULTS: The digital system has a speed that is at twice as high as least of the most sensitive analog system. Compared to the analog system, the digital system visualizes better low contrast structures such as carious defects, but shows problems in visualisation of high dynamic ranges such as crown margins or fillings: insufficient suitable dynamic range. Larger objects such as incisors could not be imaged in one exposure due to the small area of the digital detector (24.3 x 18.2 mm). Retakes may be required due to the small dynamic range and detector area. CONCLUSIONS: The complete imaging of a tooth with crown and apical region, as required in the "radiological guidelines" is in doubt with digital systems having small active areas. The image quality of digital systems differs significantly from that of analog systems, nevertheless, the achievable image quality fulfills the requirements of intraoral dental radiology.

An animal model to study microcirculatory changes associated with vascular delay.

Vascular delay is a surgical procedure that renders a flap partially ischaemic several days prior to its transfer in order to increase its viability after its transfer. Though much debate exists regarding the actual mechanism of vascular delay, most theories agree that changes in the microcirculation play a key role. In this paper, we describe four experiments that establish the ear of the homozygous (hr/hr) hairless mouse as an effective model for directly viewing and measuring delay-induced changes in microcirculation. In our first experiment, we compared mouse ears that were delayed (n = 18) with ones that were not (control) (n = 13) and showed that vascular delay significantly (P < 0.05) reduced ear flap necrosis. In a second experiment, we delayed mouse ears for 2 (n = 9), 4 (n = 14), 6 (n = 10), 8 (n = 10), 10 (n = 10), 20 (n = 18), 40 (n = 10) and 80 (n = 11) days and found that the reduction in necrosis becomes statistically significant (P < 0.05) over non-delayed controls (n = 12) after a minimum delay period of 6 days. In a third experiment, we delayed mouse ears by ligating only the vein (n = 14), only the artery (n = 11), only the nerve (sympathectomy) (n = 14), and vein, artery and nerve (n = 14) of the main neurovascular pedicle and found significant (P < 0.05) reductions in flap necrosis in all groups compared to nondelayed controls (n = 12). Finally, in a fourth experiment, we measured vessel directionality changes in mouse ears that were delayed for 6 (n = 4), 10 (n = 4), 20 (n = 4), 40 (n = 4) and 80 (n = 4) days, and found that directionality changes became significant (P < 0.05) at 6 days of delay and remained so for all the days studied when compared with non-delayed controls (n = 4).

Dose titration study of tinzaparin, a low molecular weight heparin, in patients on chronic hemodialysis.

The minimal necessary dose of Innohep (IH) (MNDI) (Innohep [tinzaparin], Leo Pharmaceutical Corp., Ballerup, Denmark) was examined in 40 patients switched from conventional heparin ([CH], Leo Pharmaceutical Corp.) to IH and in 13 patients already treated with IH. Clotting in the venous chamber and in the dialyzer was evaluated on a 4 point scale by visual inspection. IH was administrated as a bolus injection into the arterial side of the dialyzer at the beginning of dialysis sessions. The initial dose of IH was 50% of the total dose of CH used before the study (in respective IU). According to clotting in the venous chamber or dialyzer, the dose of IH was titrated by stepwise changes of 500 IU to the lowest possible dose until 3 subsequent dialysis sessions without clotting were obtained. The total dose of CH (bolus and infusion) before switching was 6,162 +/- 2,100 IU. The bleeding time from the cannulation site after dialysis, in 24 patients with A-V fistulas, was 7.1 +/- 2.8 min(triplicates). Eight patients were excluded before achieving the MNDI, 3 due to bleeding not clearly related to heparinization (1 due to gingival bleeding, 1 to epistaxis, and 1 to sugillations), 1 due to alopecia, 2 due to a need of more than 10,000 IU of IH, and 2 patients due to cessation of treatment resulting from anxiety. After switching over, the MNDI amounted to 66 +/- 26% in respective IU. The conversion IH/CH ratio correlated significantly to the blood flow rate and the type of dialyzer. When compared on 3 subsequent sessions before and after switching to IH, no differences were found in the bleeding time after decannulation and in clotting in the venous chamber while dialyzer clotting fell on the visual scale from an average of 0.36 to 0.19 (p < 0.01). No total clot formation was observed during the study. The MNDI correlated positively to the body weight, blood flow rate, and time on dialysis (with the respective coefficients of correlation of r being 0.58, 0.44, and 0.30, p < 0.05) and was also influenced by the type of dialyzer. The average MNDIs for the Hemoflow-FS hollow-fiber (Fresenius, Bad Homburg, Germany), Lundia PRO plate (Gambro, Lund, Sweden), and Polyflux hollow fiber (Gambro) were 2,571, 3,727, and 5,020 IU (p < 0.01, ANOVA). In patients on chronic hemodialysis, IH given as a bolus of 4,250 IU effectively prevented extracorporeal clotting during dialysis, similarly to CH. However, a considerable individual variation in MNDIs not related to the need for CH was observed, and this necessitates individual dosage adjustments to obtain the optimal prevention of clotting with minimal bleeding risk.

Quantification of the morphological features of a full microvascular network.

Investigations into the changes that occur in microvasculature following the surgical procedure called delay have brought about the need for a computer system capable of quantifying the morphological features of a full microvascular network in terms of average vessel length, diameter, and tortuosity. Both the formulaic conventions that have been developed to measure these quantities as well as their implementation in the form of a HP-9000/UNIX based computer software system that we developed specifically for this purpose are discussed. Reliability studies performed using the final system to measure the microcirculatory network of a mouse latissmus dorsi muscle (LDM) showed 95% confidence intervals within 5% of means and coefficients of variability within 7% of means for all quantities measured in large (150-300 microns), medium (50-150 microns), and small (< 50 microns) diameter vessels. These variations were significantly smaller than the changes that were observed in a preliminary study comparing these microvascular network parameters before and after delay in the hairless mouse LDM, showing the proposed quantification methods to be well suited to the study of the microvascular changes following delay. It is hoped that the formulaic conventions, implementation process and reliability data will provide a useful comparison for other researchers interested in measuring similar features of microcirculatory networks.

The esophageal detector device: accuracy and reliability in difficult airway settings.

INTRODUCTION: The esophageal detector device (EDD) recently has been found to assess endotracheal (ET) tube placement accurately. This study describes the reliability of the EDD in determining the position of the ET tube in clinical airway situations that are difficult. METHODS: This was a prospective, randomized, single-blinded, controlled laboratory investigation. Two airway managers (an emergency-medicine attending physician and a resident) determined ET-tube placement using the EDD in five swine in respiratory arrest. The ET tube was place in the following clinical airway situations: 1) esophagus; 2) esophagus with 1 liter of air instilled; 3) trachea; 4) trachea with 5 ml/kg water instilled; and 5) right mainstem bronchus. Anatomic location of the tube was verified by thoracotomy of the left side of the chest. RESULTS: There was 100% correlation between the resident and attending physician's use of the EDD. The EDD was 100% accurate in the determining tube placement in the esophagus, in the esophagus with 1 liter of air instilled, in the trachea, and in the right mainstem bronchus. The airway managers were only 80% accurate in detecting tracheal intubations when fluid was present. CONCLUSIONS: The EDD is an accurate and reliable device for detecting ET-tube placement in most clinical situations. Tube placement in fluid-filled trachea, lungs, or both, which occurs in pulmonary edema and drowning, may not be detected using this device.

Dust mite allergens in the office environment.

The objective of this study was to evaluate the extent of dust mite infestation and its contribution to the health complaints in office settings. The methodology recommended for residential dwellings was evaluated for use in the work environment. Der p I allergen-specific ELISA was chosen as a primary method. A liquid chromatography method for guanine is suggested as a backup method to cover a few cases where other mite species may be encountered. The levels of dust mite allergens were measured in 14 offices in response to numerous health complaints. Approximately one-half of the offices investigated were identified as having a dust mite population. Four offices showed levels of Der p I in the dust greater than 1 microgram/g. In two offices, the dust mite allergens were the source of the health complaints. In the other two offices, dust mite allergens were one of the contaminants in the office environment. In all cases, the infestation of dust mites in the offices was localized to a few specific work areas. Office chairs were the primary location where dust mites thrived. The remedial measures included regular cleanup of all fabric-covered office furnishings. Steam cleaning was recommended to eliminate dust mite populations.

Right lung ventilation in a porcine open-chest shock model.

OBJECTIVE: To determine the effect of selective right lung ventilation on gas exchange and hemodynamics when compared with bilateral lung ventilation in a porcine open-chest shock model. METHODS: A randomized, controlled laboratory investigation was performed using a static hemorrhagic shock model in 12 adult swine undergoing thoracotomy. The animals were subjected to a fixed 40% circulating blood volume hemorrhage over 20 minutes. Each animal was then assigned to either a tracheal (control) or a right mainstem (experimental) intubation group. Minute ventilation was held constant in both groups and tidal volumes were decreased by 33% in the right mainstem intubation group. Following intubation and left lateral thoracotomy, another 20% fixed-volume hemorrhage was instituted simultaneously with IV crystalloid and whole blood resuscitation for both groups over 30 minutes. Heart rate, blood pressure, and arterial blood gases were measured at 5-minute intervals. RESULTS: There was no significant difference between the control and experimental groups for any of the measured variables, including mean arterial pressure, pH, partial arterial pressure of CO2 (PaCO2), and PaO2, over time. All animals survived the study protocol. CONCLUSION: Selective right lung ventilation has no detrimental effect on gas exchange or hemodynamics when compared with standard bilateral lung ventilation in a porcine open-chest shock model.

Aurantimycins, new depsipeptide antibiotics from Streptomyces aurantiacus IMET 43917. Production, isolation, structure elucidation, and biological activity.

Aurantimycins A (1), B (2) and C (3) were isolated from the mycelium of Streptomyces aurantiacus JA 4570 as new representatives of the azinothricin group of hexadepsipeptide antibiotics. Their structures were settled by X-ray diffraction analysis of crystalline aurantimycin A (1), high field homo- and heteronuclear 2D NMR experiments, high-resolution mass spectrometry and amino acid analysis. Aurantimycins are characterized by a new side chain containing fourteen carbon atoms. They display strong activity against Gram-positive bacteria and cytotoxic effects against L-929 mouse fibroblast cells.