An elevated temperature study of a Ti adhesion layer on polyimide.

Titanium layers are used to promote adhesion between polymer substrates for flexible electronics and the Cu or Au conducting lines. Good adhesion of conducting lines in flexible circuits is critical in improving circuit performance and increasingcircuit lifetime. Nominally 50 nm thick Ti films on polyimide (PI) are investigated by fragmentation testing under uniaxial tensile load in the as-deposited state, at 350 °C, and after annealing. The cracking and buckling of the films show clear differences between the as-deposited and the thermally treated samples, cracks are much straighter and buckles are smaller following heat treatment. These changes are correlated to a drop in adhesion of the samples following heat treatment. Adhesion values are determined from the buckle dimensions using a total energy approach as described in the work of Cordill et al. (Acta Mater. 2010). Cross-sectional transmission electron microscopy of the Ti/PI interface found evidence of a ~ 5 nm thick interlayer between the largely columnar Ti and the amorphous PI. This interlayer is amorphous in the as-deposited state but nano-crystalline in those coatings tested at elevated temperature or annealed. It is put forward that this alteration of the interfacial structure causes the reduced adhesion.

Pathophysiology of hypertension and endothelial dysfunction in patients with diabetes mellitus.

There is compelling evidence for endothelial dysfunction in both type 1 and type 2 diabetics. This dysfunction is manifest as blunting of the biologic effect of a potent endothelium-derived vasodilator, nitric oxide, and increased production of vasoconstrictors such as angiotensin II, ET-1, and cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. These agents and other cytokines and growth factors whose production they stimulate cause acute increases in vascular tone, resulting in increases in blood pressure, and vascular and cardiac remodeling that contributes to the microvascular, macrovascular, and renal complications in diabetes. Reactive oxygen species, overproduced in diabetics, serve as signaling molecules that mediate many of the cellular biochemical reactions that result in these deleterious effects. Adverse vascular consequences associated with endothelial dysfunction in diabetes mellitus are Decreased nitric oxide formation, release, and action Increased formation of reactive oxygen species Decreased prostacyclin formation and release Increased formation of vasoconstrictor prostanoid Increased formation and release of ET-1 Increased lipid oxidation Increased cytokine and growth factor production Increased adhesion molecule expression Hypertension Changes in heart and vessel wall structure Acceleration of the atherosclerotic process Treatment with antioxidants and with inhibitors of the renin-angiotensin system may reverse some of the pathologic vascular changes associated with endothelial dysfunction.

Antisense inhibition of a tomato meiotic proteinase suggests functional redundancy of proteinases during microsporogenesis.

Anther development in angiosperms culminates in the programmed cell death of specific tissues to facilitate the release of pollen. Despite a wealth of morphological descriptions of this process, there have been few reports on the regulation of dehiscence or the coordination of events between tissues. We have cloned an anther-specific tomato gene encoding a serine proteinase that is expressed during meiosis and late microsporogenesis. The conceptualized tomato meiotic proteinase (TMP) is a member of a family of genes that exhibit characteristics of mammalian proprotein convertases. To examine the role of TMP in microsporogenesis, we generated transgenic plants harboring an antisense construct of the gene. Some of these plants produced little or no detectable TMP, yet no phenotypic abnormalities were observed. Zymogram analyses revealed that multiple proteinases are present in mature anthers and that proteinase activity increases as development proceeds. Taken together, these data indicate that the role of TMP during microsporogenesis, if any, may be compensated for by other proteinases.

Is there a place for combining angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists in the treatment of hypertension, renal disease or congestive heart failure?

Angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists have proven to be effective and well tolerated antihypertensive agents. They also exhibit unique cardioprotective and renoprotective properties in patients with comorbid conditions such as congestive heart failure and proteinuria or renal insufficiency. This benefit is observed most dramatically in diabetic persons. Although inconclusive, the results of a limited number of clinical trials support the notion that additive antihypertensive, cardioprotective, and renoprotective effects may be obtained with combined used of angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists in some patients. More studies are needed to confirm the findings of these preliminary studies, and to define more clearly those subsets of patients who might derive the greatest benefit from angiotensin-converting enzyme inhibitor-angiotensin II receptor subtype 1 antagonist combination therapy.

Expectant management of placenta accreta following stillbirth at term: a case report.

Placenta accreta is a rare complication of pregnancy with high rates of morbidity and mortality. We report a case of expectant management. This strategy may prevent catastrophic postpartum haemorrhage requiring peripartum hysterectomy.

Behavioural responses of piglets to castration: the effect of piglet age.

It has long been assumed that neonatal animals are less sensitive than older animals to pain, and this reasoning has been used to recommend that routine surgical procedures be performed at an early age. In this study we tested if vocal and other behavioural responses to castration increase with piglet age. Piglets (n=84) from 14 litters were assigned to one of six treatment groups: castration or sham castration at 3, 10 or 17 days of age. During the procedure castrated piglets produced high-frequency calls (>1000Hz) at more than three times the rate of piglets in the sham-castrate group. The rate of low-frequency (<1000Hz) calls was also higher for piglets in the castrate group. The rate of high-frequency calling was lower for the youngest pigs but there was no relationship between age and the effect of treatment for any of the vocal responses measured (i.e. no age by treatment interaction). During the first 2h after castration, castrated piglets spent more time sitting or standing and less time lying. During the subsequent 22h, castrated piglets spent marginally more time at the udder and less time lying down. Older piglets missed more nursings. However, the effect of castration did not vary with the age of the piglet for any measure. We conclude that while the factors affecting both the shams and the castrates (e.g. distress due to restraint) may vary with age, the pain of castration is not affected by age within the range of ages that we tested.

Factors affecting the composition and amount of 'white exudate' from cooked bacon.

Bacon sometimes produces a white, unsightly fluid that exudes from the surfaces during cooking -a phenomenon that has resulted in frequent consumer complaints. The quantity of exudate from bacon of known history was assessed subjectively, by ranking photographs following 'dry-frying', and objectively, by collecting exudate in an ice cooled tray after grilling. Trained assessors ranked samples in order of visible exudate as follows: dry cured

meiotin-1 gene expression in normal anthers and in anthers exhibiting prematurely condensed chromosomes.

We have cloned and sequenced the promoter of a meiotin-1 gene, and have determined the precise temporal and spatial pattern of meiotin-1 gene expression. The expression of the meiotin-1 gene is controlled in two increments. The meiotin-1 gene is not expressed in any of the vegetative tissues examined. Early in microsporogenesis, low levels of meiotin-1 RNA can be detected. At the onset of meiosis, there is a dramatic increase in meiotin-1 RNA levels in both tapetal and meiotic cells. However, while meiotin-1 RNA is observed in both the nucleus and cytoplasm of meiotic cells, it is found only in the nucleus of the tapetal cells. We have also examined the expression of the meiotin-1 gene in aberrant meiotic nuclei that prematurely condense their chromosomes; these nuclei have reduced levels of the meiotin-1 protein. The aberrant nuclei have only the basal level of meiotin-1 RNA; they do not exhibit the transcriptional induction seen for normal cells at the onset of meiosis. Implications for the function of meiotin-1 in regulating chromatin condensation, and in coordinating meiotic and tapetal cell activities are discussed.

Ethnic differences in nocturnal blood pressure decline in treated hypertensives.

Lack of a nocturnal decline in blood pressure (BP) has been associated with more severe end organ damage in hypertensives, and blacks appear less likely than whites to have a > 10% drop in nighttime BP ("dipping"). Little information is available about the relationship between treatment regimens, ethnic group classification, and dipping in treated hypertensive patient populations. We obtained 24-h ambulatory BP readings in 438 adult white (n = 103), black (n = 200) and Hispanic (n = 135) treated hypertensives. Tycos monitors were connected in patients' homes before their usual morning medication dose time. Research assistants administered a quality-of-life questionnaire, recorded patients' drug regimen, and observed the patients take their morning dose. Monitors were programmed to record BP every 30 min. Dippers were defined as persons who had a drop of > or = 10% decline in average daytime (08:00 to 22:00) compared to nighttime (00:00 to 04:00) BP. Logistic regression modeling was used to assess the relationship between demographic and treatment variables and probability of dipping. Twenty-four-hour average BP was similar in all three ethnic groups. However, the absence of a systolic dip was significantly more common in black and Hispanic men than in white men (OR black v white = 11.54, 95% CI = 3.92 to 34.01; OR Hispanic v white = 7.32, 95% CI = 2.47 to 21.68). There were no ethnic group differences in probability of systolic dipping among women. Absence of a diastolic dip was approximately twice as common in blacks and Hispanics than in whites, with no marked gender-by-ethnic-group interaction in the magnitude of the association. Of the 10 most commonly prescribed antihypertensives, no single drug was positively associated with nocturnal BP decline. Later versus earlier morning dose time, but not once-a-day dosing, was associated with absence of dipping. Treated black and Hispanic hypertensives are less likely to "dip" than non-Hispanic whites. No particular drug was positively associated with dipping.

Prolonged fenoldopam infusions in patients with mild to moderate hypertension: pharmacodynamic and pharmacokinetic effects.

Thirty-three patients with mild-to-moderate essential hypertension received either placebo or fenoldopam, a selective dopamine-1 agonist, by intravenous infusion at a fixed infusion rate ranging from 0.1 to 0.8 microg/kg/min for 48 h during a double-blind, placebo-controlled, randomized inpatient clinical trial. Blood pressure and heart rate were measured every 15 min for 24 h before, during, and 24 h after the 48-h drug infusion. Plasma concentrations of racemic fenoldopam were measured at frequent intervals during and for 24 h after fenoldopam infusion. In the 26 patients who received fenoldopam, there were dose-dependent reductions in systolic and diastolic blood pressure, which usually reached a nadir within 2 h of beginning infusion and were significant even at the lowest dose studied (-9 and -9 mm Hg for systolic and diastolic blood pressure, respectively, at 24 h for the dose of 0.04 microg/kg/min, P < .05). There were associated increases in heart rate that were greater in the first than in the last 24 h of drug infusion. Compared to the average 24-h control blood pressure, maximum mean reductions in systolic and diastolic blood pressures of 33 and 21 mm Hg, respectively, were noted in patients receiving fenoldopam at 0.8 microg/kg/min and occurred 4 and 1 h, respectively, after beginning infusion. Tolerance to the blood pressure lowering effects of the drug developed slowly during the 48 h of drug infusion; the half-life for this effect was 60 h. No serious adverse clinical effects were noted in any patient. These results demonstrate that fenoldopam is effective in reducing blood pressure of patients with mild-to-moderate hypertension at doses as low as 0.04 microg/kg/min, is well tolerated at doses up to 0.8 microg/kg/min, maintains most of its antihypertensive efficacy throughout 48 h of continuous, constant rate infusion, and produces neither prolonged pharmacodynamic effects nor rebound hypertension when discontinued. The pharmacodynamic effects of the drug are best predicted by pharmacokinetics of racemic and R-fenoldopam.

Retinal hemorrhages caused by accidental household trauma.

Traumatic retinal hemorrhages in young children are considered pathognomonic of child abuse. We identified 3 children with unilateral retinal hemorrhages caused by accidental household trauma. The hemorrhages were ipsilateral to intracranial hemorrhage and isolated to the posterior retinal pole.

Sustained hemodynamic effects of the selective dopamine-1 agonist, fenoldopam, during 48-hour infusions in hypertensive patients: a dose-tolerability study.

Eight patients with stage I-II hypertension received a continuous IV infusion of the selective dopamine-1 agonist, fenoldopam, for up to 48 hours at rates from 0.4 to 1.9 micrograms/kg/min. Hemodynamics and clinical symptoms during infusion were compared to the same parameters in the 24-hour periods before and after infusion. Fenoldopam lowered blood pressure and increased heart rate. Greatest changes occurred during the first 12 hours of infusion and gradually returned toward preinfusion values throughout the remaining 36 hours in the six patients who completed 48 hours of infusion. Fenoldopam was discontinued within 2 hours of starting the infusion in two patients who received drug rates of 0.9 microgram/kg/min and 1.9 micrograms/kg/min because of precipitous bradycardia. Clinical symptoms noted at fenoldopam doses higher than 0.8 microgram/kg/min were headache, dizziness, diaphoresis, nausea and vomiting, and restlessness. In this pilot study, fenoldopam effectively reduced blood pressure in patients with stage I-II hypertension for up to 48 hours, but fixed-dose infusion rates above 0.8 microgram/kg/min were associated with a high frequency of clinically significant and often intolerable adverse effects.

The sympathetic nervous system and baroreflexes in hypertension and hypotension.

Blood pressure and blood volume are closely regulated by the interrelated actions of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Reflex vasoconstriction caused by parallel SNS and RAAS activation is modulated by two interactive negative feedback systems called baroreflex. The aortic-carotid baroreflex systems respond to momentary changes in systolic blood pressure, adjusting the degree of SNS-dependent peripheral vasoconstriction and cardiac output to allow maintenance of a relatively constant perfusion pressure. Cardiopulmonary baroreflexes respond to momentary changes in cardiac filling, adjusting the degree of peripheral venoconstriction and venous return to maintain cardiac preload and stroke volume. Under normal conditions, each baroreflex system exhibits a degree of tonic negative feedback so that it can alter SNS output immediately, providing counterregulatory increases or decreases in pressure or volume to maintain homeostasis. The SNS is inappropriately active in obesity and hypertension and plays a causal or permissive role in all forms of chronic hypertension. If the negative feedback control exerted by the baroreflexes over the SNS and renin-angiotensin-aldosterone system (RAAS) were perfect, chronic hypertension would not occur. Activity of the baroreflexes, however, is chronically altered by maladaptive changes such as cardiac and vascular fibrosis and hypertrophy. Long-term increases in SNS and RAAS activity also exert ongoing deleterious effects on the heart and vasculature by directly facilitating further cardiac hypertrophy and arterial stiffening. These effects appear to contribute to a vicious cycle of chronic hypertension and target organ damage. Other syndromes of abnormal blood pressure (BP) control, including orthostatic hypotension and baroreflex failure are examples of abnormal baroreflex activity and SNS control.

The case for combining angiotensin-converting enzyme inhibitors and calcium-channel blockers.

Tight blood pressure control among diabetic and nondiabetic patients with hypertension is perhaps the single most effective intervention used to delay progression to end-stage renal disease (ESRD). The renoprotective actions of angiotensin-converting enzyme (ACE) inhibitors in patients with diabetic and hypertensive nephropathy is well established. Drugs of this class fairly uniformly reduce glomerulosclerosis, delay the deterioration in renal function, and improve proteinuria, a predictive surrogate marker for renal injury. Calcium- channel blockers (CCBs) in the phenylalkylamine (verapamil) and benzothiazepine (diltiazem) classes also improve proteinuria and delay the progression of renal disease in diabetic and nondiabetic hypertensive nephropathy beyond that attributable to blood pressure control. The short-acting dihydropyridine CCBs worsen proteinuria and accelerate renal injury in both animal models and humans with hypertension or diabetes. A very limited number of studies in animals or humans with hypertension or diabetes have demonstrated at least an additive renoprotective effect when the combination of ACE inhibitors and nondihydropyridine CCBs has been compared with each agent administered as monotherapy. Because patients with impaired renal function and either hypertension or diabetes appear to benefit from aggressive blood pressure reduction, many of these patients will require two or more drugs to achieve the currently recommended blood pressure goals. Combinations of ACE inhibitor and CCB are attractive because they may provide better blood pressure control, appear to be better tolerated with fewer side effects than either drug alone, and may exert a greater renoprotective effect in patients at risk for renal failure than either an ACE inhibitor or a CCB.

Injection of water and polyphosphate into pork to improve juiciness and tenderness after cooking.

Two injection levels (5 and 10%) and three concentrations of polyphosphate (0, 3 and 5%) were used in 64 pork loin portions to assess the influence of polyphosphate injection on eating quality of pork steaks cooked by grilling to a centre temperature of 72.5 or 80°C and assessed by a trained ten member sensory panel. Polyphosphate improved water holding, and generally produced more tender and more juicy meat than control steaks, although pork flavour intensity was reduced and abnormal flavour intensity increased. Raising the centre temperature from 72.5 to 80°C increased the cooking loss from 35 to 42%, reduced tenderness, juiciness and abnormal flavours and increased pork flavour intensity. Steaks containing 5% polyphosphate and cooked to 80°C were more tender and as juicy as steaks without polyphosphate cooked to the lower centre temperature. These effects were generally larger than those that can be achieved `naturally' by, for example, changing diets and breeds but whether the technology will be utilised in an increasingly `additive free' climate is debatable.

Peritonitis causes diaphragm weakness in rats.

Respiratory failure is a common and often lethal complication of severe peritonitis. Because this inflammatory process develops in the abdomen, adjacent to the diaphragm, we hypothesized that peritonitis might directly compromise diaphragm function. We tested this hypothesis using male Sprague-Dawley rats. We injected oyster glycogen into the rats' peritoneum, and 16 h later the peritoneum was lavaged for leukocyte analysis and muscle samples were excised. Contractile properties of diaphragm fiber bundles were measured in vitro. We found that neutrophils and macrophages were concentrated in peritoneal lavage fluid of experimental animals (p < 0.01) and were adherent to the abdominal surface of the diaphragm. Immunohistochemistry showed increases in inducible nitric oxide synthase in microvessels of the diaphragm and limb skeletal muscles but not in heart or spleen. Peritonitis decreased maximal force production by the diaphragm (23.6+/-0.6 versus 21.2+/-0.6 N/cm2; p < 0.05) and decreased the absolute forces developed at physiologic stimulus frequencies (> 30 Hz; p < 0.01), depressing the overall force-frequency relationship (p < 0.001). Peritonitis had little effect on acute muscular fatigue. These data demonstrate that peritonitis weakens the diaphragm in rats and suggest that humans with peritonitis may be predisposed to respiratory muscle dysfunction.

Antihypertensive and vasodilator actions of antioxidants in spontaneously hypertensive rats.

This study was designed to determine whether the antioxidants ascorbic acid, aminotriazole, and glutathione acutely reduce blood pressure (BP) by endothelium-independent or -dependent vasorelaxation in spontaneously hypertensive rats. Blood pressure of male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) was measured before and 4 h after administration of antioxidants. Thoracic aortic rings with and without endothelium were suspended in organ chambers for isometric tension recordings. Each of the antioxidants, administered in vivo, significantly decreased blood pressure in SHR but had no significant effect on BP in WKY rats. The endothelium-dependent impaired relaxation of SHR aortic rings to acetylcholine (ACh) was improved by prior in vivo administration of each antioxidant. ACh-induced relaxations of aortic rings from WKY was not affected by prior antioxidant treatment. Addition of each antioxidant directly to the organ chamber containing SHR or WKY aortas produced dose- and endothelium-dependent relaxations. Moreover, antioxidant pretreatment of SHR aortic rings significantly potentiated ACh-induced relaxations in these aortas, suggesting that this effect was endothelium dependent. Relaxations induced by the antioxidants alone or by ACh in the presence of antioxidants were inhibited by addition of either xanthine plus xanthine oxidase or nitro-L-arginine. These findings suggest that either excess production of oxidants or a deficiency of antioxidant systems may contribute to the high blood pressure and the endothelium-dependent impairment of vascular relaxation in SHR.