Effect of pepper extracts on the viability kinetics, topography and Quantitative NanoMechanics (QNM) of Campylobacter jejuni evaluated with AFM.

Campylobacter jejuni is a pathogen bacterium that causes foodborne gastroenteritis in humans. However, phenolic compounds extracted from natural sources such as capsicum pepper plant (Capsicum annuum L. var. aviculare) could inhibit the growth of C. jejuni. Therefore, different extracts were prepared using ultrasonic extraction (USE), conventional extraction (CE) and thermosonic extraction (TSE). C. jejuni was then exposed to chili extracts to examine the antimicrobial effect and their growth/death bacterial kinetics were studied using different mathematical models. Atomic force microscopy was applied to investigate the microstructural and nanomechanical changes in the bacteria. Extracts obtained by TSE had the highest phenolic content (4.59 ± 0.03 mg/g of chili fresh weight [FW]) in comparison to USE (4.12 ± 0.05 mg/g of chili FW) and CE (4.28 ± 0.07 mg/g of chili FW). The inactivation of C. jejuni was more efficient when thermosonic extract was used. The Gompertz model was the most suitable mathematical model to describe the inactivation kinetics of C. jejuni. Roughness and nanomechanical analysis performed by atomic force microscopy (AFM) provided evidence that the chili extracts had significant effects on morphology, surface, and the reduced Young's modulus of C. jejuni. The novelty of this work was integrating growth/death bacterial kinetics of C. jejuni using different mathematical models and chili extracts, and its relationship with the morphological, topographic and nanomechanical changes estimated by AFM.

Genetic associations between visual scores, body weight and age at first calving in nellore breed cattle / Associações genéticas entre escores visuais, peso corporal e idade ao primeiro parto de bovinos da raça Nelore

Body weight records of 231,416 Nellore females obtained from the Brazilian Association of Zebu Breeders were used to determine a linear combination between visual appraisal scores (body structure, precocity and muscling) using principal components analysis (PC), and to verify their genetic association with body weight at 12 months (BW) and age at first calving (AFC). The mixed linear model included the fixed effect of the contemporary group and the linear and quadratic effects of age at calving, random effects of genetic additive, maternal environment and temporary environment. Heritability estimates for BW, PC and AFC were 0.51, 0.30 and 0.17, respectively. Genetic additive correlations between BW and PC; BW and AFC, and PC and AFC were 0.48; -0.31 and -0.55; respectively. Spearman's correlations for the best-ranked bulls based on PC prediction were positive between BW and PC and negative among the other combinations. Heritability estimates and correlations indicate potential genetic gains for BW and CP with reduced AFC in cows. The use of PC allows positive responses on precocity and body weight development.(AU)

Utilizaram-se registros de pesos corporais de 231.416 fêmeas bovinas da raça Nelore, oriundos dos registros da Associação Brasileira de Criadores de Zebu-ABCZ, com o objetivo de estabelecer, por componentes principais, uma combinação linear (CP) das características de escores visuais de estrutura (E), precocidade (P) e musculosidade (M), bem como verificar sua associação genética com o peso corporal aos 12 meses (PC) e à idade ao primeiro parto (IPP). O modelo linear misto utilizado incluiu os efeitos fixos de grupo de contemporâneos e os efeitos linear e quadrático da idade da vaca ao parto, os efeitos aleatórios genético aditivo, ambiente materno e ambiente temporário. Estimativas de herdabilidade para PC, CP e IPP foram iguais a 0,51; 0,30 e 0,17, respectivamente. Correlações genéticas aditivas entre PC e CP; PC e IPP; e, ainda, CP e IPP foram iguais a 0,48; -0,31 e -0,55, respectivamente. As correlações de Spearman para os melhores reprodutores classificados em relação à predição de CP foram positivas entre PC e CP e negativas entre as demais combinações. Estimativas de herdabilidade e de correlações indicam possibilidade de ganhos genéticos expressivos para PC e CP com redução para IPP nas fêmeas. A utilização de CP possibilita respostas favoráveis para precocidade sexual e desenvolvimento ponderal.(AU)

Genetic association of productive and reproductive traits with stayability in Nellore cattle: analysis using Bayesian models.

We evaluated the genetic association of growth traits [weight adjusted to 205 days of age (W205), 365 days of age (W365), and 550 days of age (W550); weight gain between 205 days of age and 365 days of age (WG1) and between 365 days of age and 550 days of age (WG2)] and reproductive traits [age at first calving (AFC); first calving interval (FCI)] with stayability in the herd (STAY), using Bayesian inference in linear and threshold models. We defined STAY as the probability of a cow calving three or more times before the age of 76 months, given that she had calved at least once. We assigned binary codes (0, failure; 1, success) to each female. We used a sire model for analysis and formed different contemporary groups for the investigated traits. We analyzed the results by applying a two-trait sire model that included STAY (threshold trait) and linear traits (W205, W365, W550, WG1, WG2, AFC, and FCI). We used Gibbs sampling to estimate variance components and heritabilities. In all the analyses, we found that the mean heritability estimates for STAY were of moderate magnitude (0.20-0.25). The mean heritabilities for W205, W365, W550, WG1, WG2, AFC, and FCI were 0.20, 0.23, 0.39, 0.08, 0.14, 0.12, and 0.11, respectively. We observed wide variation in the posterior distributions of genetic correlations; however, with the exception of those obtained for the reproductive traits, the mean estimates were of low magnitude. Selection for WG2 can results in favorable correlated response in STAY.

Estimates of genetic parameters for reproductive traits in Brahman cattle breed.

This study was designed to estimate genetic parameters for the following traits of Brahman cattle in Brazil: age at first calving (AFC), calving interval (CI), rebreeding (REB), and stayability (STAY). For REB, the value 1 was assigned to heifers that rebred and calved after first calving and the value 0 was assigned to heifers that failed to rebreed after first calving. Likewise, for STAY, the value 1 was assigned to cows that calved at least 3 times by the time they reach 6 yr of age; otherwise, the value 0 was assigned. A bivariate analysis was used to estimate covariances components by using linear animal model for CI and AFC and threshold animal model for REB and STAY. The mean h(2) were 0.10, 0.02, 0.22, and 0.10 for AFC, CI, REB, and STAY, respectively. The genetic correlations were ­0.13 between AFC and CI, ­0.35 between AFC and REB, ­0.57 between AFC and STAY, and 0.32 between REB and STAY, which reveal that cows that remain productive for longer periods in the herd also start breeding younger and present greater chances to REB. The selection of Brahman cattle for reproductive traits, such as AFC, CI, REB, and STAY, will render low magnitude and long-term responses.

Genetic evaluation of milk yield in Alpine goats for the first four lactations using random regression models.

Random regression models have been used in evaluating test-day milk yield, providing accurate estimates of genetic values in animals. However, herd evaluation with only information from the first lactation may not be the best option from an economic perspective. Other factors should be taken into account, particularly other lactations. Our objective in this study was to analyze the genetic divergence between the first four lactations of Alpine goats. The RENPED software was used to perform descriptive statistics, check for errors in pedigree, recode the data, and for Pearson's and Spearman's correlations. The WOMBAT software was used to estimate the variance components and predict the breeding values. The CALC software was adopted to calculate the percentage of coincidence between the ranking of the animals and the animals kept in common at each lactation evaluation. The results show that selection using only the first lactation in small herds with a low degree of technology can be employed as a palliative measure, in view of the difficulty in evaluating all lactations. However, the selection of breeding goats and the production of catalogues should not be based only on the first lactation, because the results demonstrate inversions in the classification of the best breeders when other lactations are analyzed.

Obesity and the "obesity paradox" in cardiovascular diseases.

Obesity adversely affects most cardiovascular (CV) risk factors and is strongly associated, probably as an independent risk factor, with most CV diseases. However, substantial evidence points to the existence of an "obesity paradox," in that overweight and obese patients with established CV diseases typically have a better prognosis than leaner patients with the same CV disease. Despite this paradox, we believe that the "weight" of evidence still supports efforts at purposeful weight loss in both primary and secondary CV prevention.

Ventricular-vascular uncoupling increases expression of B-type natriuretic peptide in heart transplantation.

BACKGROUND: Allograft adaptation to a foreign circulation is imperfect as noted from persistent limitations to stress. Effective arterial elastance (Ea), a measure of afterload, provides an estimate of aortic impedance. End systolic elastance (Ees) is a load-independent measure of ventricular performance as well as its interaction in the periphery. The ratio (Ea to Ees) characterizes ventricular-vascular coupling; a value close to unity signifies poor mechanical efficiency. The purpose of this investigation was to correlate mechanical efficiency of work with expression of B-type natriuretic peptide BNP, a specific marker of ventricular stress and strain. METHODS: We measured BNP levels in 40 consecutive stable heart transplant recipients free from rejection. In addition, echocardiography was performed to obtain Ea, Ees, and their ratio (Ea to Ees) by the single-beat method. We examined correlates of BNP expression by assessing Ea to Ees, while correcting for mean arterial pressure, body mass index, left ventricular mass index, ejection fraction, and serum creatinine. RESULTS: BNP levels were significantly and positively correlated (r=0.38, P=.05) with an increased Ea to Ees ratio. By multivariable analysis, this relationship persisted independently (t=2.1, P=.04), while the five other measures were insignificant predictors. CONCLUSION: This investigation indicated that the transplanted heart demonstrates poor contractile efficiency and operates at maximal left ventricular work. This is paralleled by a tandem increase in BNP, suggesting that elevation in this stress peptide is at least partly explained by ventriculo-vascular uncoupling in heart transplantation, independent of alterations in blood pressure.

Corticosteroid weaning in the tacrolimus and mycophenolate era in heart transplantation: clinical and neurohormonal benefits.

BACKGROUND: Compared with cyclosporine, tacrolimus-based immunosuppression yields improved metabolic outcomes in heart transplantation. Whether corticosteroid freedom provides incremental metabolic benefits in tacrolimus and mycophenolate mofetil immunoprophylaxis remains uncertain. METHODS: In a prospective trial, 41 heart transplant patients treated with tacrolimus and mycophenolate mofetil underwent steroid weaning immediately after transplantation until weaning was complete. Weaning was interrupted only for treated rejection with or without hemodynamic compromise. Benefits of steroid weaning assessed following the first year included B-type natriuretic peptide (BNP), late infections, lipids, blood pressure, hyperglycemia, and body mass index (BMI). RESULTS: Of this 41 patient cohort (age 53 +/- 9 years, 50% black American, 35% women) followed for a total of 47 +/- 5 months, 25 had corticosteroids discontinued (62%) by an average of 20 +/- 11 months. No differences between the two groups were noted in baseline characteristics. Significant predictors of failure to wean steroids included higher rejection, BNP, and lower dose of mycophenolate mofetil. No significant benefits of steroid weaning were noted on lipids, blood pressure, hyperglycemia, and BMI. However, late infections (after 1 year) requiring hospitalizations were more frequent in the failure to wean group (0.60.4 vs 0 infections/patient/y, P <.001). INFERENCES: Unlike known metabolic benefits of steroid withdrawal with cyclosporine, heart transplant recipients treated with tacrolimus and mycophenolate mofetil demonstrate no incremental metabolic benefits, but instead experience benefits of decreased serious late infections. Furthermore, failure to discontinue corticosteroids in this series is predicted by early allograft rejection, use of lower doses of mycophenolate mofetil, and higher BNP levels suggesting poor cardiac adaptation.

Treatment of heart failure according to William Stokes: the enchanted mercury.

BACKGROUND: It was not until 1919 that the diuretic properties of mercury were observed in patients with syphilis; in the same year the beneficial effects of mercurial diuretics were shown in a patient with severe rheumatic heart disease and anasarca. However, mercury had been used much earlier for the treatment of dropsy without clear guidelines. In this article we describe William Stokes' insights into the treatment of heart failure, focusing on the beneficial diuretic properties of mercury. METHODS: We reviewed the chapter "Treatment of the Weak and Probably Dilated Heart in Connexion With Enlargement of the Liver and Pulmonary Disease" in William Stokes' famous treatise The Diseases of the Heart and the Aorta. CONCLUSIONS: Stokes makes several important clinical observations. First, he provides precise guidelines on when and how to use mercury in these patients. Second, he realizes the importance of mercury for the treatment of decompensated heart failure. Stokes recognizes the cyclical nature of frequent decompensation in congestive heart failure, the relationship of clinical deterioration and reduced urine output, and the importance of reestablishing urinary flow to ameliorate dyspnea. Third, he attempts to define the mechanism of action "... if any of the characteristic action of mercury can be perceived unless we include diuresis." Finally, he gives interesting guidelines on the dosage and side effects of mercury. These observations on the treatment of "congestive" heart failure are an important contribution to the understanding of heart failure pathophysiology and the design of prescription regimens for this disease.

Desperate diseases, desperate measures: tackling malignant hypertension in the 1950s.

BACKGROUND: The conquest of malignant hypertension is one of the most important medical achievements of the second half of the 20th century. As we enter the new millennium, it is critical to examine the efforts that have led to our ability to treat this once incurable disease. METHODS: Review was performed of the literature from 1900 to the 1950s regarding the etiology, clinical evaluation, and treatment of hypertension, focusing on malignant hypertension. RESULTS: Fifty years ago, in a time of sparse treatment options, the occurrence of malignant hypertension was a dreaded event that taxed the aptitude of the clinician. Confronted with an "extreme disease," physicians chose to use "extreme methods of cure" in conformity with the teaching of Hippocrates. In the 1950s malignant hypertension was treated with such drastic measures as rice diet, sympathectomy, and intravenous pyrogens. CONCLUSIONS: In the practice of medicine today, while work is being done to reassert biomolecular mechanisms, we still face patients who have reached the end stages of failure and manifest devastating morbidity. These patients are subjected to "extreme therapies" reminiscent of those that surrounded malignant hypertension in the past. In an era when adequate treatment of hypertension has become a reality for so many patients, it is appropriate to give credit to those who paved the way to such great progress.

Role of vascular remodeling in the pathogenesis of early transplant coronary artery disease: a multicenter prospective intravascular ultrasound study.

BACKGROUND: Luminal narrowing in transplant coronary artery disease is thought to be primarily caused by intimal proliferation, and the role of vascular remodeling is less certain. METHODS AND RESULTS: We studied cardiac allografts from 83 prospectively recruited patients immediately and 1 year after transplant using intravascular ultrasound in a multicenter study. We measured coronary artery dimensions in 310 angiographically matched segments (175 were also fully matched by ultrasound criteria). At 1 year, lumen area changed by -1.8 +/- 3.7 mm(2) (p < 0.0001, 14% of baseline lumen area). Thirty-three percent of this luminal loss was due to intimal thickening and 67% to vessel shrinkage. Shrinkage also occurred (-0.9 +/- 3.2 mm(2), 7% of baseline total area) in segments free of detectable intimal disease at baseline and at 1 year. Using the mean baseline total vessel area (13.9 mm(2)) as the cutoff, we divided the cohort into the large and the small coronary-segment groups. The large-segment group (n = 176) shrank more (-2.6 +/- 4.4 vs. -0.03 +/- 2.8 mm(2), p < 0.0001), but intimal growth was similar in both groups (0.8 +/- 2.2 vs. 0.4 +/- 1.3 mm(2), p = not significant). Analysis of the 175 fully ultrasound matched sub-cohort showed similar results. Changes in intimal area, total vessel area, and lumen area were similar in segments with (n = 132) and segments without (n = 178) pre-existing donor disease. Despite overall shrinkage, change in total vessel area positively correlated with change in intimal area (r = 0.29, p < 0.0001). CONCLUSION: In large coronary segments, coronary artery shrinkage plays an important role in the loss of luminal diameter early after cardiac transplantation, whereas new intimal growth occurs in both large and small segments. Pre-existent donor disease does not aggravate these processes. Compensatory remodeling with increasing intimal growth retards the rate of lumen loss. As is intimal thickening, shrinkage and compensatory remodeling are important pathogenic mechanisms in transplant coronary artery disease.

Recent developments in microvascular angina.

Microvascular angina (Syndrome X) is an extremely heterogeneous clinical entity that is the product of genetic, coronary microvascular, metabolic, and clinical factors, which combine together to produce distinct cardiac manifestations and complications. The interactions of these abnormalities remain poorly understood. The diagnosis is considered in patients with anginal symptoms and no epicardial coronary narrowing. Therapy is also problematic, with beta-blockers as first-line pharmacotherapy followed by angiotensin-converting enzyme inhibitors and calcium channel blockers.

Historical perspectives on cardiac transplantation: the past as prologue to challenges for the 21st century.

The development of cardiac transplantation is based on experimental studies that started in the beginning of the last century. The improvement in the surgical technique for cardiac transplantation, associated with other progress in the field of cardiac surgery and a better understanding of the immune responses, allowed cardiac transplantation to become a reality for the treatment of endstage heart disease. Recent development in immunosuppressive agents and advances in cardiac surgery have meant that cardiac transplantation is not a "fantastic speculation for the future," but a reality for the present. Thus, cardiac transplantation is performed around the world with an excellent survival rate and has become a lifesaving treatment for many patients with severe heart disease.

Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine--results at 24 months after transplantation.

BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.

Insights into ventricular repolarization abnormalities in cardiac allograft vasculopathy.

We investigated the relationship of QT dispersion and cardiac allograft vasculopathy in heart transplant recipients. The findings suggest that the development of cardiac allograft vasculopathy is associated with an increase in QT dispersion, suggesting the presence of abnormal repolarization in these patients.

Difficult cases in heart failure: Raison d'Être behind ACE inhibitors and AT1 receptor combinations in chronic heart failure: chemical nuances or clinical significance?

The following case description serves to illustrate the difficulties often faced in clinical practice in implementing what appear to be fairly simple and clear evidence-based guidelines regarding angiotensin-converting enzyme (ACE) inhibitors and no clear guidelines regarding angiotensin receptor blocker (ARB) use or, more importantly, ACE inhibitor and ARB combinations in chronic heart failure. (c)2001 by CHF, Inc.