A neotropical perspective on the uniqueness of the Holocene among interglacials.

Understanding how tropical systems have responded to large-scale climate change, such as glacial-interglacial oscillations, and how human impacts have altered those responses is key to current and future ecology. A sedimentary record recovered from Lake Junín, in the Peruvian Andes (4085 m elevation) spans the last 670,000 years and represents the longest continuous and empirically-dated record of tropical vegetation change to date. Spanning seven glacial-interglacial oscillations, fossil pollen and charcoal recovered from the core showed the general dominance of grasslands, although during the warmest times some Andean forest trees grew above their modern limits near the lake. Fire was very rare until the last 12,000 years, when humans were in the landscape. Here we show that, due to human activity, our present interglacial, the Holocene, has a distinctive vegetation composition and ecological trajectory compared with six previous interglacials. Our data reinforce the view that modern vegetation assemblages of high Andean grasslands and the presence of a defined tree line are aspects of a human-modified landscape.

Psychiatric nurses' perspectives of spirituality and spiritual needs during an amalgamation.

The purpose of this study was to explore the meaning of spirituality and how the spiritual needs of psychiatric nurses could be supported at work during a hospital amalgamation. Forty-six nurses completed the General Information Questionnaire and described the meaning of spirituality and how their spiritual needs could be supported. Data were analysed by the double-coding qualitative method. The themes identified for the meaning of spirituality included: being hopeful, having belief/belief systems, maintaining relatedness/connectedness and the expression of spirituality. The major themes identified to support nursing staffs' spiritual needs at work included communication, offering hope, being valued and support from spiritual sources. Nurses expressed the importance of spirituality in their lives and the need for spiritual support at work. Data for addressing staff spiritual needs are reported; however, further studies are needed to understand the spiritual needs of nursing staff at work during hospital amalgamations.

Selective inhibitors of monoamine oxidase (MAO). 5. 1-Substituted phenoxathiin inhibitors containing no nitrogen that inhibit MAO A by binding it to a hydrophobic site.

It is believed that a monoamine oxidase (MAO) inhibitor specific for MAO A, which is reversibly bound to this enzyme and displaceable by tyramine, will be an antidepressant which will not cause a rise in blood pressure when tyramine-containing foods are ingested. Some linear tricyclic compounds with a larger and a smaller group forming the central ring and with a lipophilic group ortho to the larger group (here mostly the SO2 function of phenoxathiin 10,10-dioxide) are reported to have the sought properties. Potency appears to require short length and relatively small cross section for the substituent. The 1-ethyl (13), 1-vinyl (22), 1-trifluoromethyl (27), and 1-iodo (76) phenoxathiin dioxides had the best profiles. Structure-activity relationships, syntheses, and a possible rationale for the selectivity of these compounds and related tricyclics are given. Compound 13 was selected for further development. A summary of pharmacological data for 13 is given.

Supplemental L-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury.

Unenhanced hypothermic cardioplegia does not prevent postischemic endothelial and contractile dysfunction in hearts subjected to antecedent regional or global ischemia. This study tested the hypothesis that supplementing blood cardioplegic solution and reperfusion with the nitric oxide precursor L-arginine would preserve endothelial function, reduce infarct size, and reverse postcardioplegia regional contractile dysfunction by the L-arginine-nitric oxide pathway. In 23 anesthetized dogs, the left anterior descending coronary artery was ligated for 90 minutes, after which total bypass was established for surgical "revascularization." In 10 dogs, unsupplemented multidose hypothermic blood cardioplegic solution was administered for a total of 60 minutes of cardioplegic arrest. In eight dogs, L-arginine was given intravenously (4 mg/kg per minute) and in blood cardioplegic solution (10 mmol) during arrest. In five dogs, the nitric oxide synthesis blocker N omega-nitro-L-arginine (1 mmol) was used to block the L-arginine-nitric oxide pathway during cardioplegia and reperfusion. Infarct size (triphenyltetrazolium chloride) as percent of the area at risk was significantly reduced by L-arginine compared with blood cardioplegic solution (28.2% +/- 4.1% versus 40.5% +/- 3.5%) and was reversed by N omega-nitro-L-arginine to 68.9% +/- 3.0% (p < 0.05). Postischemic regional segmental work in millimeters of mercury per millimeter (sonomicrometry) was significantly better with L-arginine (92 +/- 15) versus blood cardioplegic solution (28 +/- 3) and N omega-nitro-L-arginine (26 +/- 6). Segmental diastolic stiffness was significantly lower with L-arginine (0.46 +/- 0.06) compared with blood cardioplegic solution (1.10 +/- 0.11) and was significantly greater with N omega-nitro-L-arginine (2.70 +/- 0.43). In ischemic-reperfused left anterior descending coronary arterial vascular rings, maximum relaxation responses to acetylcholine, the stimulator of endothelial nitric oxide, was depressed in the blood cardioplegic solution group (77% +/- 4%) and was significantly reversed by L-arginine (92% +/- 3%). Smooth muscle function was unaffected in all groups. We conclude that cardioplegic solution supplemented with L-arginine reduces infarct size, preserves postischemic systolic and diastolic regional function, and prevents arterial endothelial dysfunction via the L-arginine-nitric oxide pathway.

Adenosine in blood cardioplegia prevents postischemic dysfunction in ischemically injured hearts.

Adenosine (ADO) is an endogenous cardioprotective autacoid that exerts receptor-mediated cardioprotection from ischemic-reperfusion injury. This study tested the hypothesis that blood cardioplegia (BCP) supplemented with ADO reduces postischemic left ventricular dysfunction in ischemically injured hearts. Twenty-one anesthetized dogs on total bypass were subjected to 30 minutes of normothermic global ischemia. Cold (4 degrees C) potassium BCP was then delivered every 20 minutes for 60 minutes of cardioplegic arrest. In 7 dogs, unsupplemented BCP was used; in 7 dogs, BCP was supplemented with 400 mumol/L ADO; and, in 7 dogs, ADO receptors were blocked with 8-p-sulfophenyltheophylline (30 mg/kg) given with 400 mumol/L ADO in BCP. Preischemic and postischemic left ventricular systolic function was assessed by the slope and volume axis intercept of the end-systolic pressure-volume (impedance catheter) relationship (ESPVR). In unsupplemented BCP, the postischemic slope of the ESPVR was significantly depressed by 42% versus the preischemic value (from 6.8 +/- 1.2 mm Hg/mL to 3.9 +/- 0.4 mm Hg/mL; p < 0.05 versus the preischemic value). In contrast, BCP supplemented with ADO was found to restore the postischemic ESPVR slope to preischemic levels (7.7 +/- 1.0 mm Hg/mL versus 7.4 +/- 1.2 mm Hg/mL, respectively). This cardioprotection was reversed by 8-p-sulfophenyltheophylline (9.9 +/- 1.5 mm Hg/mL versus 4.5 +/- 0.7 mm Hg/mL; p < 0.05 versus the preischemic value). Postischemic plasma creatinine kinase activity was elevated equally in all groups over the baseline values. We conclude that ADO in BCP attenuates postcardioplegia dysfunction in severely injured hearts through the operation of receptor-mediated mechanisms.

Feasibility of using neural networks to estimate minimum tumour temperature and perfusion values.

We examine the ability of neural networks to estimate the tissue perfusion values present and the minimum temperature in numerically calculated (Pennes, Bioheat Transfer Equation) steady-state hyperthermia temperature fields based on a limited number of measured temperatures within this field A hierarchical system of neural networks consisting of a first layer of pattern recognizing neural networks and a second layer of hypersurface reconstructing neural networks is shown to be capable of estimating these variables within a selected error tolerance. The results indicate that estimating the minimum tumour temperature directly with the system of neural networks may be more effective than using the indirect method of numerically recreating a temperature field with perfusion estimates and then obtaining the minimum tumour temperature from the estimated temperature field. Additional results indicate that if the locations of the measured temperatures within the temperature field are selected appropriately, the hierarchical system of neural networks can tolerate a moderate level of model mismatch. This model mismatch can come from errors in modelling the tumour boundaries, the sensor locations, or the magnitude of the power deposition. This paper is not intended to assess or demonstrate clinical applicability but to be a first step in investigating the feasibility of neural networks for parameter estimation related to hyperthermia studies.

Acadesine improves surgical myocardial protection with blood cardioplegia in ischemically injured canine hearts.

BACKGROUND: Adenosine is a cardioprotective autacoid that exerts receptor-mediated protection from ischemia/reperfusion injury. In ischemically injured hearts, avoidance of ischemia/reperfusion injury with hypothermic chemical cardioplegia may be incomplete, and consequently, postischemic left ventricular (LV) function may be severely depressed and chamber stiffness increased. This study tested the hypothesis that the adenosine-regulating agent acadesine improves myocardial protection with hypothermic blood cardioplegia (BCP), resulting in better postischemic LV function and diastolic characteristics in hearts injured by 45 minutes of normothermic global ischemia. METHODS AND RESULTS: Eighteen anesthetized (350 micrograms fentanyl citrate, 5 mg diazepam) dogs on total vented bypass were randomized to receive vehicle (n = 5), low-dose acadesine (LDA, 0.125 mg.kg-1.min-1, n = 6) or high-dose acadesine (HDA, 0.5 mg.kg-1.min-1, n = 7) continuously infused 30 minutes before global ischemia and discontinued 10 minutes after aortic cross-clamp removal. Hearts were protected with cold (4 degrees C) multidose (every 20 minutes) potassium BCP, which contained saline vehicle, 1 mg/L acadesine (LDA), or 4 mg/L acadesine (HDA) for a total of 1 hour of cardioplegic arrest. Postischemic LV function, assessed by the slope of the end-systolic pressure-volume (impedance catheter) relation, was depressed by 34 +/- 7% of baseline (5.6 +/- 1.0 versus 2.7 +/- 0.7 mm Hg/mL, P < .05) in vehicle. With LDA, there was variable improvement in postischemic function (5.1 +/- 1.3 versus 3.6 +/- 0.6 mm Hg/mL, P = .26 versus baseline). In contrast, there was complete postischemic functional recovery with HDA (5.9 +/- 0.6 versus 5.2 +/- 0.8 mm Hg/mL, P = .54). Postischemic chamber stiffness was preserved in both LDA and HDA. CONCLUSIONS: We conclude that the higher dose of acadesine improves myocardial protection when used as a pretreatment and BCP adjuvant, resulting in better postischemic LV systolic function and diastolic characteristics.

Protection from ischaemic-reperfusion injury with adenosine pretreatment is reversed by inhibition of ATP sensitive potassium channels.

OBJECTIVE: The aim was to test the hypothesis that the cardioprotective effects against ischaemic-reperfusion injury of pretreatment with adenosine are mediated in part by activation of ATP sensitive potassium channels (K+ATP channels). METHODS: 42 anaesthetised New Zealand White rabbits underwent 30 min coronary occlusion, followed by 2 h reperfusion. Half the animals received a 5 min infusion of 140 micrograms.kg-1.min-1 of adenosine as pretreatment. The remainder of the animals received a 5 min infusion of saline alone as pretreatment. Animals pretreated with adenosine received either a low dose of the K+ATP channel blocker glibenclamide (0.3 mg.kg-1), high dose glibenclamide (3.0 mg.kg-1), or vehicle immediately prior to ischaemia to test whether glibenclamide can reverse the protective effects of adenosine, thus allowing the adenosine effect but antagonising K(+)ATP channel activation during ischaemia. Animals which received saline pretreatment also received low dose glibenclamide, high dose glibenclamide, or vehicle (controls) to evaluate the effect of glibenclamide alone. Infarct size was determined with tetrazolium and Unisperse Blue stains, and transmural blood flow was measured using radioactive microspheres. RESULTS: Although there were no differences in collateral myocardial blood flow during ischaemia or in risk area among the groups, infarct size was reduced by adenosine pretreatment to 8 (SEM 3)% v 36(4)% in controls (p < 0.05). K(+)ATP channel blockade with low dose glibenclamide in saline pretreated animals did not by itself extend the degree of necrosis [33(4)%], whereas low dose glibenclamide prevented the protective effects of adenosine pretreatment [38(3)%]. High dose glibenclamide reversed adenosine protection as well [54(3)%], but at a dose which increased infarct size in saline pretreated animals [52(3)%]. CONCLUSIONS: While adenosine pretreatment protects against necrosis in the rabbit, (1) the expression of this protection depends at least in part upon the actions of K(+)ATP channels during ischaemia, and (2) glibenclamide at higher doses increases infarct size, suggesting either that the K(+)ATP channel is endogenously protective during ischaemia, or that the higher dose has other infarct extending effects.

Is coffee consumption a contributor to cardiovascular disease? Insights from the Framingham Study.

Reported coffee consumption during 1954 to 1958 and 1971 to 1973 was used to test for association with cardiovascular disease (CVD) incidence and lipid values in the Framingham cohort. Multivariate analysis was employed, regressing CVD on age, systolic pressure, cigarette use, body mass index, total cholesterol, and coffee intake. In pooled analyses (2648 men with 549 CVD cases and 3566 women with 462 CVD cases) coffee intake was not associated with CVD incidence in either smokers or nonsmokers, irrespective of sex. Similarly, multivariate analyses for individuals with existing cardiovascular disease showed no association between coffee intake and subsequent cardiovascular disease. In men significant negative associations between coffee and total cholesterol, and very-low-density lipoprotein cholesterol were seen, whereas in women positive associations with low-density lipoprotein cholesterol were observed. Although inconsistent effects on the lipid profile were seen, no increase in primary or secondary CVD was seen with coffee drinking.

Synthesis and antiherpes simplex virus activity of 9-[(1,3-dihydroxy-2-propylthio)methyl]guanine.

The synthesis of the thio analogue (thio-DHPG, 2) of 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) is described. The synthesis of 2 proceeded via the condensation of acetoxymethyl sulfide 9 with diacetylguanine 10 to give the protected nucleoside analogue 11. Although catalytic hydrogenolysis failed, the benzyl ether functionalities of 11 were successfully cleaved by an acetolysis reaction to furnish 14. Ammonolysis of 14 gave 2, which was also transformed to sulfoxide 15 and sulfone 16. Preliminary in vitro screening indicated that 2 exhibited comparable activity to DHPG against herpes simplex virus type 1 (HSV-1) but was less active against the type 2 virus (HSV-2) and human cytomegalovirus (HCMV). In a mouse encephalitis model (HSV-2), subcutaneous treatment with 2 led to a 53% reduction in mortality at a dose of 100 mg/kg per day.