Management of mango hopper, Idioscopus clypealis, using chemical insecticides and Neem oil.

An experiment was conducted in Field Laboratory, Department of Entomology at Bangladesh Agricultural University, Mymensingh, during 2013 to manage the mango hopper, Idioscopus clypealis L, using three chemical insecticides, Imidacloprid (0.3%), Endosulfan (0.5%), and Cypermethrin (0.4%), and natural Neem oil (3%) with three replications of each. All the treatments were significantly effective in managing mango hopper in comparison to the control. Imidacloprid showed the highest efficacy in percentage of reduction of hopper population (92.50 ± 9.02) at 72 hours after treatment in case of 2nd spray. It also showed the highest overall percentage of reduction (88.59 ± 8.64) of hopper population and less toxicity to natural enemies including green ant, spider, and lacewing of mango hopper. In case of biopesticide, azadirachtin based Neem oil was found effective against mango hopper as 48.35, 60.15, and 56.54% reduction after 24, 72, and 168 hours of spraying, respectively, which was comparable with Cypermethrin as there was no statistically significant difference after 168 hours of spray. Natural enemies were also higher after 1st and 2nd spray in case of Neem oil.

Efficacy of combined formulations of fungicides with different modes of action in controlling botrytis gray mold disease in chickpea.

Botrytis gray mold (BGM) caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L.) and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur) in Bangladesh for three years (2008, 2009, and 2010). Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%)], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%), and Protaf 250EC, propiconazole (0.05%)], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%); Secure 600 WG, phenomadone + mancozeb (0.2%); and Companion, mancozeb 63% + carbendazim 12% (0.2%)]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1-9 scale) and the highest increase (38%) of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance.

Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans.

The purpose of this study was to investigate the association of visit-to-visit and 24-h blood pressure (BP) variability with markers of endothelial injury and vascular function. We recruited 72 African Americans who were non-diabetic, non-smoking and free of cardiovascular (CV) and renal disease. Office BP was measured at three visits and 24-h ambulatory BP monitoring was conducted to measure visit-to-visit and 24-h BP variability, respectively. The 5-min time-course of brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were assessed as measures of endothelial and smooth muscle function. Fasted blood samples were analyzed for circulating endothelial microparticles (EMPs). Significantly lower CD31+CD42- EMPs were found in participants with high visit-to-visit systolic blood pressure (SBP) variability or high 24-h diastolic blood pressure (DBP) variability. Participants with high visit-to-visit DBP variability had significantly lower flow-mediated dilation and higher nitroglycerin-mediated dilation at multiple time-points. When analyzed as continuous variables, 24-h mean arterial pressure variability was inversely associated with CD62+ EMPs; visit-to-visit DBP variability was inversely associated with flow-mediated dilation normalized by smooth muscle function and was positively associated with nitroglycerin-mediated dilation; and 24-h DBP variability was positively associated with nitroglycerin-mediated dilation. All associations were independent of age, gender, body mass index and mean BP. In conclusion, in this cohort of African Americans visit-to-visit and 24-h BP variability were associated with measures of endothelial injury, endothelial function and smooth muscle function. These results suggest that BP variability may influence the pathogenesis of CV disease, in part, through influences on vascular health.

Pyrazinoindolone inhibitors of MAPKAP-K2.

Optimization of pyrazinoindolone inhibitors of MAPKAP-K2 (MK2) provides a reasonable balance of cellular potency and physicochemical properties. Mechanistic studies support the inhibition of MK2 which is responsible for the sub-micromolar cellular efficacy.

Differential protein expression profiles in the hippocampus of human alcoholics.

Mild to severe cognitive impairments are frequently observed symptoms in chronic alcoholics. Decline of cognitive function significantly affects patients' recovery process and prognosis. The hippocampal region is sensitive to the effects of alcohol and it has been suggested that alcohol-induced hippocampal damage and/or changes in neuronal circuitry play an important role in generating these symptoms. Although various hypotheses have been proposed, molecular mechanisms underlying these alterations in the hippocampus are largely unknown. In the present study, we employed a 2DE-based proteomics approach to compare the protein expression profiles of the hippocampus in human alcoholic and healthy control brains. In the alcoholic hippocampus, 20 protein spots were found to be differentially regulated, 2 increased and 18 decreased. Seventeen proteins were identified using mass spectroscopy and were subcategorized into three energy metabolic proteins, six protein metabolic proteins, four signalling proteins, two oxidative stress-related proteins, one vesicle trafficking protein and one cytoskeletal protein. Some of these proteins have been previously implicated in alcohol-induced brain pathology. Based upon the results, several hypotheses were generated to explain the mechanisms underlying possible functional and/or structural alterations induced by chronic alcohol use in this brain region.

Efficacy of terazosin and finasteride in symptomatic benign prostatic hyperplasia: A comparative study.

Medical treatment for symptomatic Benign Prostatic Hyperplasia (BPH) has become popular for the last few years. This study was designed to find out and compare the efficacy of terazosin, a alpha1 adrenoceptor blocker and finasteride, a 5alpha-reductase inhibitor in symptomatic BPH. A total of 60 patients (30 in terazosin group and 30 finasteride group) of symptomatic BPH were selected. Terazosin group received 1 mg daily at bedtime for 3 days, 2 mg at bedtime for 7 days, thereafter 5 mg at bedtime daily for 6 months. Finasteride group received 5 mg once daily. In terazosin treated patients, improvement after 3 months were as follows, IPSS 3.93 +/- .74 points reduction, Qmax 2.13 +/- .68 ml/s increase, post-voided residual urine volume (PVR) 20.67 +/- 10.56 ml reduction (significant, p<0.001) and prostate volume 0.57 +/- 1.54 ml reduction (not significant). Similar statistical differences were observed at 6 months follow up. In finasteride treated patients, improvements after 3 months were as follows, International Prostate Symptom Score (IPSS) 1.38 +/- .63 points reduction, Qmax 0.55 +/- 0.78 ml/s increase, PVR 5.93 +/- 7.64 ml reduction (significant, p<0.001) and prostate volume 0.17 +/- 5.6 ml reduction (non-significant). At 6 month follow up statistical differences were significant in all parameters including prostate volume 4.57 +/- 5.30 ml reduction (p<0.001). In comparison, statistically significant superiority of terazosin over finasteride was found in improving IPSS, Qmax and PVR in both follow up visits. But terazosin had nonsignificant effect in reducing prostate volume; in contrast, finasteride had significant effect in second visit. It can be concluded from this study that terazosin 5mg once daily is effective in mild to moderate cases of symptomatic BPH. On the other hand, finasteride 5mg once daily may be useful in large prostate and to be given for at least 6 months.

Possible involvement of phosphoinositide-Ca2+ signaling in the regulation of alpha-amylase expression and germination of rice seed (Oryza sativa L.).

We have studied the effects of neomycin, a potent inhibitor of inositol phospholipid-specific phospholipase C (PLC), on the germination of rice seed and the gibberellin-induced expression of alpha-amylase in the aleurone layer and the scutellar tissues. It was shown that, in the absence of exogenous Ca2+, neomycin markedly reduced the germination speed and seedling growth of rice seeds and inhibited the gibberellin-induced expression of alpha-amylase in both secretory tissues. In addition, neomycin decreased the formation of inositol 1,4,5-trisphosphate (IP3) in the gibberellin-treated aleurone layer and the scutellar tissues. However, the inhibitory effects on the germination speed and the expression of alpha-amylase activity were overcome by supplementation of Ca2+. In addition, gibberellin elevated the level of IP3, and ABA prevented the gibberellin-induced formation of IP3, although ABA alone did not alter the IP3 level. The expression of a membrane-bound PLC molecule in rice aleurone layer was shown to be induced by gibberellin, and the gibberellin-induced expression of PLC was markedly delayed by treatment with ABA. These results strongly suggest that the phosphoinositide-Ca2+ signal transduction pathway may play an important role in the gibberellin-induced expression of alpha-amylase molecules closely related to the germination processes of rice seed.

Inhibition of allergen-induced pulmonary responses by the selective tryptase inhibitor 1,5-bis-[4-[(3-carbamimidoyl-benzenesulfonylamino)-methyl]-phenoxy]-pen tane (AMG-126737).

Emerging evidence suggests that mast cell tryptase is a therapeutic target for the treatment of asthma. The effects of this serine protease are associated with both pathophysiologic pulmonary responses and pathologic changes of the asthmatic airway. In this study, the tryptase inhibitor 1,5-bis-[4-[(3-carbamimidoyl-benzenesulfonylamino)-methyl]-p henoxy]-pentane (AMG-126737) was evaluated for its pharmacologic effects against allergen-induced airway responses. AMG-126737 is a potent inhibitor of human lung mast cell tryptase (Ki = 90 nM), with greater than 10- to 200-fold selectivity versus other serine proteases. Intratracheal administration of AMG-126737 inhibited the development of airway hyperresponsiveness in allergen-challenged guinea pigs with an ED50 of 0.015 mg/kg. In addition, the compound exhibited oral activity in the guinea pig model. The in vivo activity of AMG-126737 was confirmed in a sheep model of allergen-induced airway responses, where the compound inhibited early and late phase bronchoconstriction responses and the development of airway hyperresponsiveness. These results support the proposed role of tryptase in the pathology of asthma and suggest that AMG-126737 has potential therapeutic utility in this pulmonary disorder.

Potent selective nonpeptidic inhibitors of human lung tryptase.

Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure-activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented.

Secretory leukocyte protease inhibitor prevents allergen-induced pulmonary responses in animal models of asthma.

Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways that exhibits broad spectrum inhibitory activity against mast cell and leukocyte serine proteases implicated in asthma pathology. To assess the potential therapeutic utility of SLPI in this disorder, its effects on antigen-induced pulmonary responses were evaluated. In Ascaris-sensitized sheep, SLPI (3 mg) administered by aerosol daily for 4 days, with the final dose 0.5 h before antigen challenge, reduced the areas under the curve for early- and late-phase bronchoconstriction (73 and 95%, respectively; p <.05 versus control responses). SLPI also inhibited the development of airway hyperresponsiveness to carbachol (84%, p <. 05 versus control response) measured 24 h after antigen challenge. In ovalbumin-sensitized guinea pigs, intratracheal administration of SLPI daily for 3 days, with the final dose 1 h before antigen challenge, inhibited the development of airway hyperresponsiveness to histamine with an ED50 of <0.05 mg/kg. Prolonged pharmacodynamic activity of SLPI was observed in both species. In a murine model of atopic asthma, SLPI inhibited leukocyte influx into the airways after chronic allergen challenge. SLPI administered to sheep by the predosing protocol described above also prevented the antigen-induced decrease of tracheal mucus velocity (p <.05). In addition, a single aerosol administration of SLPI (30 mg) to sheep 1 h after antigen challenge inhibited the subsequent late-phase bronchoconstriction and development of hyperresponsiveness and reversed the stimulated decrease in tracheal mucus velocity. These results suggest that SLPI may provide therapeutic intervention against the pathophysiology of asthma and its underlying pathology.

Inhibition of murine neutrophil serine proteinases by human and murine secretory leukocyte protease inhibitor.

Human secretory leukocyte protease inhibitor (SLPI) is a predominant physiologic inhibitor of elastase and cathepsin G, proinflammatory serine proteases released by activated neutrophils. In order to fully evaluate the potential pharmacologic efficacy of human SLPI in animal models of inflammation, it is critical to know the potency of the inhibitor for corresponding proteases from the species of interest. In this report, we compare the inhibitory activity of human and murine SLPI against elastase and cathepsin G from both species. Human and murine neutrophil elastase and cathepsin G display comparable Km values for their specific peptide substrates. Murine SLPI inhibits murine neutrophil elastase and cathepsin G with Ki values of 5 and 0.12 nM, respectively, while human SLPI inhibits the both murine serine proteases with Ki's of 0.02 nM. In contrast, murine SLPI inhibits human neutrophil elastase and cathepsin G with Ki values of 1.4 and 90 nM, respectively, while human SLPI inhibits the proteases with Ki's of 0.3 and 10 nM, respectively. These results demonstrate species-specific variations in the protease inhibitory activities of SLPI. Such variations should be considered in the evaluation of the activity of human SLPI in murine pharmacologic models.

Detection system for reaction-rate analysis in a low-volume proteinase-inhibition assay.

High-throughput screening of large combinatorial chemical libraries in biochemical assays will benefit from reduced reagent volume and increased speed of measurement. Standard assays typically are performed in 96-well microtiter plates having 200-microL well volumes and up to an hour of incubation time. In this paper, we demonstrate a technique for precise and rapid measurement of the progress of an enzymatic reaction and its inhibition with reduced volume and time (for this work, the assay was mixed at the 200-microL level and detected in 2-microL volumes with minutes of total assay time). Directly measuring the enzyme activity in the small volume format yields a precise value for the median inhibitory concentration (IC50) of an inhibitor compound. The model assay is the endoproteolytic cleavage of a small fluorogenic peptide by human neutrophil collagenase (MMP-8). The fluorogenic peptide was labeled at one end with a UV/blue fluorophore (N-methylanthranilyl) and at the other end with a quencher (dinitrophenol). To generate inhibition data, a hydroxamate peptide analog inhibitor of collagenase, actinonin, was included in the reaction. The experiments were performed using ultraviolet laser illumination (325 nm wavelength) and parallel fluorescence detection by a cooled, charge-coupled-device camera system to increase sensitivity and speed. The assay volume was reduced to 2 microL for data collection, and the total time for mixing, incubation, and measurement was less than 6 min. For comparison to a standard format, the same assay was performed in a 96-well microtiter plate in 200 microL using 30 min of incubation and measurement in a microtiter plate fluorimeter. Median inhibitory concentrations (IC50) for actinonin of 73 +/- 16 and 100 +/- 14 nM were obtained in the 2- and 200-microL assays, respectively. One concern with assay miniaturization and increases in throughput is a potential loss of precision and accuracy. Laser excitation and parallel detection of fluorescence is a promising approach for increased speed and reduced cost without loss of precision for proteinase inhibition assays.

Effects of cardiomyoplasty on right ventricular filling during volume loading.

BACKGROUND: Although cardiomyoplasty (CMP) is thought to improve ventricular systolic function, its effects on ventricular diastolic function are not clear. Especially the effects on right ventricular diastolic filling have not been fully investigated. Because pericardial influences are more pronounced in the right ventricle than in the left ventricle, CMP with its external constraint may substantially impair right ventricular diastolic filling. METHODS: Fourteen purebred adult beagles were used in this study. Seven underwent left posterior CMP, and 7 underwent a sham operation with a pericardiotomy and served as controls. Four weeks later, the hemodynamic effects of CMP were evaluated by heart catheterization before and after volume loading (central venous infusion of 10 mg/kg of 4.5% albumin solution for 5 minutes). RESULTS: In the CMP group, mean right atrial pressure and right ventricular end-diastolic pressure increased significantly from 3.1 +/- 1.2 mm Hg to 6.1 +/- 2.0 mm Hg (p < 0.001) and from 4.0 +/- 1.8 mm Hg to 9.6 +/- 2.5 mm Hg (p < 0.001), respectively. Volume loading in the control group did not significantly increase either variable. Right ventricular end-diastolic volume and stroke volume did not change significantly (from 53 +/- 9.3 mL to 60 +/- 9.0 mL and from 20 +/- 2.3 mL to 21 +/- 3.2 mL, respectively) in the CMP group. In the control group, however, right ventricular end-diastolic volume and stroke volume increased significantly from 45 +/- 7.7 mL to 63 +/- 14 mL (p < 0.05) and from 18 +/- 4.3 mL to 22 +/- 4.2 mL (p < 0.05), respectively. CONCLUSIONS: These results suggest that CMP may reduce right ventricular compliance and restrict right ventricular diastolic filling in response to rapid volume loading because of its external constraint.

Interaction of secretory leukocyte protease inhibitor with heparin inhibits proteases involved in asthma.

Protease inhibition by secretory leukocyte protease inhibitor (SLPI) is accelerated by the sulfated polysaccharides. The nature of the SLPI-polysaccharide interaction, explored with affinity chromatography, indicated that this interaction was sensitive to the charge and type of polysaccharide. Dextran and chondroitin had the lowest affinity for SLPI, followed by dermatan, heparan, and dextran sulfates. While heparin bound SLPI tightly, the highest affinity heparin chains unexpectedly contained a lower level of sulfation than more weakly interacting chains. Heparin oligosaccharides, prepared using heparin lyase I were SLPI-affinity fractionated. Surprisingly, undersulfated heparin oligosaccharides bound SLPI with the highest affinity, suggesting the importance of free hydroxyl groups for high affinity interaction. Isothermal titration calorimetry was used to determine the thermodynamics of SLPI interaction with a low molecular weight heparin, an undersulfated decasaccharide and a tetrasaccharide. The studies showed 12-14 saccharide units, corresponding to molecular weight of approximately 4,800, were required for a 1:1 (SLPI:heparin) binding stoichiometry. Furthermore, an undersulfated decasaccharide was able to bind SLPI tightly (Kd approximately 13 nM), resulting in its activation and the inhibition of neutrophil elastase and pancreatic chymotrypsin. The in vitro assessment of heparin and the decasaccharide and tetrasaccharide using stopped-flow kinetics suggested that heparin was the optimal choice to study SLPI-based in vivo protease inhibition. SLPI and heparin were co-administered by inhalation in therapy against antigen-induced airway hyperresponsiveness in a sheep bronchoprovocation model. Heparin, in combination with SLPI demonstrated in vivo efficacy reducing early and late phase bronchoconstriction. Heparin also increased the therapeutic activity of SLPI against antigen-induced airway hyperresponsiveness.

Effects of (+)-8',8',8'-trifluoroabscisic acid on alpha-amylase expression and sugar accumulation in rice cells.

The effects of (+)-8',8',8'-trifluoroabscisic acid (trifluoro-ABA) on alpha-amylase expression were studied in rice embryoless half-seeds, scutella, and suspension-cultured cells derived from the embryo, and the effects of the analog on sugar accumulation were also studied in scutella and suspension-cultured cells. Treatment with (+)-trifluoro-ABA strongly inhibited the gibberellic acid-inducible expression of alpha-amylase I-1 encoded by RAmy1A in the aleurone layers of embryoless half-seeds at the levels of transcription, protein synthesis, and enzyme activity. It was also found that (+)-trifluoro-ABA stimulated (i) the uptake of glucose from the incubation medium and (ii) the synthesis of sucrose in scutellar tissues and suspension-cultured cells of rice. The biological activity of (+)-trifluoro-ABA was found to be more potent and persistent than that of natural ABA. We further examined the effects of trifluoro-ABA on the expression of alpha-amylase I-1 in scutellar tissues and suspension-cultured cells. It was found that (+)-trifluoro-ABA did not inhibit the formation of alpha-amylase I-1 in the absence of external glucose. However, glucose and (+)-trifluoro-ABA cooperatively suppressed the formation of alpha-amylase I-1. Judging from these results, we conclude that the regulatory mechanism for the expression of alpha-amylase I-1 in the scutellar epithelium is distinguishable from that operating in the aleurone layer.

A canine model of dilated cardiomyopathy induced by repetitive intracoronary doxorubicin administration.

OBJECTIVE: A simple and reproducible large animal model of dilated cardiomyopathy has yet to be developed. This study was performed to establish a canine model of dilated cardiomyopathy. METHODS: Six closed-chest pure-bred beagles weighing 8 to 12 kg (10 +/- 1.9 kg) underwent intracoronary infusion of doxorubicin (Adriamycin). Low-dose (0.7 mg/kg) doxorubicin was infused into the left main coronary artery through a 5F Judkins catheter. Infusions were repeated weekly for 5 weeks. We evaluated the effects on cardiac hemodynamics, chamber size, the neuroendocrine system, and cardiac ultrastructure before and 1 and 3 months after five intracoronary infusions of doxorubicin. RESULTS: Three months after treatment, fractional shortening (mean +/- standard error of the mean) had decreased from 36.5% +/- 0.8% to 21.7% +/- 1.4% (p = 0.0003), and left ventricular ejection fraction had decreased from 71.0% +/- 3.3% to 36.3% +/- 5.5% (p = 0.001). The left ventricular diastolic dimension had increased from 27.8 +/- 0.9 to 35.5 +/- 0.6 mm (p = 0.003), and the left ventricular end-diastolic volume had increased from 27.5 +/- 1.8 to 38.3 +/- 1.9 ml (p = 0.015). Left ventricular end-diastolic pressure had increased from 8.5 +/- 0.9 to 14.5 +/- 1.1 mm Hg (p = 0.01), and the stroke volume had decreased from 16.7 +/- 0.9 to 11.5 +/- 0.4 ml (p = 0.001). During the same period, the plasma norepinephrine concentration also increased from 114 +/- 27.4 to 423 +/- 88.9 pg/ml (p = 0.024), and plasma atrial natriuretic peptide levels increased from 33.8 +/- 7.0 to 76.5 +/- 14.8 pg/ml (p = 0.012). Histologic changes such as myofiber atrophy and cytoplasmic vacuolation, accompanied with interstitial fibrosis, were found predominantly in the left ventricle. CONCLUSION: Repeated intracoronary infusions of doxorubicin represent a simple and reliable technique to produce dilated cardiomyopathy in the dog. This model can be used to evaluate the effects of new therapies, especially surgical treatments such as dynamic cardiomyoplasty and reduction ventriculoplasty, on dilated cardiomyopathy.

Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi.

Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequence, tryptase inhibitors have become the subject of study as potential novel therapeutic agents for asthma. Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways which exhibits anti-tryptase activity. To assess the potential therapeutic utility of SLPI in asthma, its effects were evaluated using in vitro and ex vivo models of airway hyperresponsiveness and compared with the effects of the small molecule tryptase inhibitor APC-366. Our results demonstrate that SLPI inhibits tryptase-mediated hyperresponsiveness in vitro and attenuates the hyperresponsiveness observed in airway smooth muscle from antigen-sensitized animals subjected to antigen exposure. The small molecule tryptase inhibitor APC-366 has a similar inhibitory effect. Thus, tryptase appears to be a significant contributor to the development of hyperresponsiveness in these models. To the extent that tryptase contributes to the development and progression of asthma, SLPI may possess therapeutic potential in this disease setting.

The cloning and characterization of a murine secretory leukocyte protease inhibitor cDNA.

Human secretory leukocyte protease inhibitor (hSLPI) is produced by epithelial cells at mucosal surfaces, where it regulates both the neutrophil-mediated inflammation that characterizes inflammatory diseases, and pathogens themselves via both antiprotease and "defensin-like" activities. Additionally, hSLPI may regulate other processes such as cutaneous desquamation and placental invasiveness. To better understand the primary physiologic roles of SLPI, it will be important to establish a genetically tractable animal model, the most attractive candidate being the mouse. In this report, the cloning and characterization of murine (m) SLPI is described. mSLPI is encoded by a single copy gene, and appears structurally highly similar to hSLPI. At the same time, significant differences between mSLPI and hSLPI are presented, notably a difference in expression pattern, and a structural difference in the protease binding site that correlates with a difference in the spectrum of protease inhibiton. Such species-specific evolution of this protease inhibitor is notable given that species-specific structure-function differences have previously been reported for the alpha-1 antitrypsin family.

Effect of dynamic cardiomyoplasty on phasic coronary arterial flow velocity in canine hearts.

The usefulness of dynamic cardiomyoplasty has been demonstrated repeatedly, both experimentally and clinically. Although clinical applications of dynamic cardiomyoplasty to ischemic heart disease have been reported, its effect on the coronary blood flow has never been discussed. Therefore, we tested the hypothesis that dynamic cardiomyoplasty might adversely affect coronary arterial blood flow through compression of the coronary arteries during systolic skeletal muscular contraction and incomplete relaxation of the skeletal muscle flap during diastole. Dynamic cardiomyoplasty was performed in seven mongrel dogs with the use of a left latissimus dorsi-muscle flap, paced synchronously with the R wave of the electrocardiogram. A 3F Doppler catheter was placed in the left main trunk of the coronary artery to assess the instantaneous changes of coronary flow velocity by fast Fourier transformation analysis, We compared systolic and diastolic properties during assisted versus unassisted cardiac cycles by calculating the peak velocity and the time-velocity integral. During assisted cardiac cycles, a significant enhancement of coronary arterial blood flow velocity was demonstrated by significant increases in both systolic and diastolic peak velocity (26.9% +/- 6.5%, p < 0.005; 4.0% +/- 1.6%, p < 0.05, respectively) and time-velocity integral (20.9% +/- 4.8%, p < 0.05; 10.0% +/- 4.6%, p < 0.05, respectively). Enhancement of coronary arterial blood flow velocity was associated with an increase in mean aortic pressure (16.4% +/- 1.3%, p < 0.005) and descending aortic flow (67.5% +/- 5.3%, p < 0.005). Also, the improved systolic coronary arterial blood flow velocity was consistent with an increase in systolic aortic pressure (15.8% +/- 1.5%, p < 0.005), and enhancement of diastolic coronary arterial blood flow velocity was associated with an increase in diastolic aortic pressure (8.6% +/- 2.3%, p < 0.01). We concluded that coronary arterial blood flow velocity was increased by the enhancement of cardiac function as a result of dynamic cardiomyoplasty, leading to an increase of coronary perfusion pressure and cardiac output.