Current perspectives on defining and mitigating frailty in relation to critical illness.

Up to half of ICU survivors, many of whom were premorbidly well, will have residual functional and/or cognitive impairment and be vulnerable to future health problems. Frailty describes vulnerability to poor resolution of homeostasis after a stressor event but it is not clear whether the vulnerability seen after ICU correlates with clinical measures of frailty. In clinical practice, the scales most commonly used in critically ill patients are based on the assessment of severity and survival. Identification and monitoring of frailty in the ICU may be an alternative or complimentary approach, particularly if it helps explain vulnerability during the recovery and rehabilitation period. The purpose of this review is to discuss the use of tools to assess frailty status in the critically ill, and consider their importance in clinical practice. Amongst these, we consider biomarkers with potential to identify patients at greater or lesser risk of developing post-ICU vulnerability.

Influence of intermittent fasting on myocardial infarction-induced cardiac remodeling.

BACKGROUND: Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival. METHODS: Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL - fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF - fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations. RESULTS: Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 µm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and ß-myosin heavy chain did not differ between groups. CONCLUSION: Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.

Anthropometric changes caused by hepatitis C treatment with interferon and ribavirin: which patients and which measures are affected?

BACKGROUND: Chronic hepatitis C causes chronic hepatic inflammation, which can lead to cirrhosis, terminal liver failure, and hepatocellular carcinoma. The treatment aims to achieve viral clearance, but the usage of pegylated interferon and ribavirin is linked to side effects such as severe weight loss, which can lead to complications and treatment discontinuation. The aim of this study was to investigate which anthropometric measures were more affected in patients with chronic hepatitis C during 24 weeks of treatment with pegy lated interferon and ribavirin. Then, the influence of age, sex, hepatic fibrosis stage, and ribavirin doses on each measure was also evaluated. METHODS: Seventy-six patients were included and their weight, triceps skin fold thickness, arm circumference, middle-arm muscle circumference, and corrected arm muscle area were measured before and after 24 weeks of treatment. Epidemiological data and liver biopsy findings were obtained from patients' records. The sample was divided into two groups: one with advanced hepatic fibrosis and another group with mild to moderate fibrosis. Comparisons into each group were made using Wilcoxon or paired tests. After that, a linear regression model was applied to estimate the anthropometric changes during the treatment according to age, sex, hepatic fibrosis stage, and ribavirin doses. RESULTS: The subjects suffered reductions of important anthropometric measures, mainly related to fat mass (p<0.001).Some decrease of fat-free mass was also observed in subjects with advanced fibrosis. The statistic model showed that age and sex were more associated with the anthropometric changes observed. CONCLUSIONS: In conclusion, the antiviral treatment caused loss of relevant anthropometric measures, and the model proposed was able to estimate some of them

Serum Vitamin A and Inflammatory Markers in Individuals with and without Chronic Obstructive Pulmonary Disease.

BACKGROUND: Vitamin A is essential for the preservation and integrity of the lung epithelium and exerts anti-inflammatory effects. OBJECTIVE: Evaluating vitamin A in the serum and sputum and testing its correlation with inflammatory markers in individuals with or without COPD. Methods. We evaluated dietary intake, serum and sputum vitamin A, tumor necrosis factor alpha, interleukin- (IL-) 6, IL-8, and C-reactive protein in 50 COPD patients (age = 64.0 ± 8.8 y; FEV1 (forced expiratory volume in the first second) (%) = 49.8 ± 16.8) and 50 controls (age = 48.5 ± 7.4 y; FEV1 (%) = 110.0 ± 15.7). RESULTS: COPD exhibited lower serum vitamin A (1.8 (1.2-2.1) versus 2.1 (1.8-2.4) µmol/L, P < 0.001) and lower vitamin A intake (636.9 (339.6-1349.6) versus 918.0 (592.1-1654.6) RAE, P = 0.05) when compared with controls. Sputum concentration of vitamin A was not different between groups. Sputum vitamin A and neutrophils were negatively correlated (R (2) = -0.26; P = 0.03). Smoking (0.197, P = 0.042) exhibited positive association with serum vitamin A. COPD was associated with lower serum concentrations of vitamin A without relationship with the systemic inflammation. CONCLUSIONS: Serum concentration of vitamin A is negatively associated with the presence of COPD and positively associated with smoking status. Sputum retinol is quantifiable and is negatively influenced by neutrophils. Although COPD patients exhibited increased inflammation it was not associated with serum retinol.

Prevalence of iodine intake inadequacy in elderly Brazilian women. A cross-sectional study.

BACKGROUND/OBJECTIVES: Inadequate iodine intake is still a problem in various regions of the world, and limited data exist regarding the ingestion of iodine in elderly people. We investigated the prevalence of iodine intake inadequacy in a group of elderly women living in a region of Brazil considered to be iodine-sufficient. DESIGN AND SETTING: Cross-sectional study conducted in the public healthcare system of Bauru, São Paulo, Brazil. METHODS: We evaluated 135 elderly women (average age of 68.2 years) who participated in a program of assistance to the elderly with respect to iodine intake through two 24-hour recalls using a nutritional computer program. The women were also evaluated with respect to serum levels of free thyroxin (FT4) and thyrotropin (TSH) and were classified as euthyroid, hypothyroid or hyperthyroid. RESULTS: The average iodine intake of the group was 100.7 ± 39.2 µg. Twenty-nine patients (21.5%) presented thyroid dysfunction: 27 (20%) had hypothyroidism, and two (1.5%) had hyperthyroidism. The average iodine intake of the patients with hypothyroidism and euthyroidism was 92.7 µg and 101.7 µg, respectively. The prevalence of iodine intake inadequacy, considering the co-variables of age, race, income, body mass index, TSH, FT4 and arterial hypertension, was 51%, 48% and 66% in the general, euthyroid and hypothyroid patients, respectively. CONCLUSION: We concluded that high prevalence of iodine intake inadequacy was present in this group of elderly women living in a region of Brazil considered to be iodine-sufficient.

Effect of three exercise programs on patients with chronic obstructive pulmonary disease.

We compared the effect of three different exercise programs on patients with chronic obstructive pulmonary disease including strength training at 50_80% of one-repetition maximum (1-RM) (ST; N = 11), low-intensity general training (LGT; N = 13), or combined training groups (CT; N = 11). Body composition, muscle strength, treadmill endurance test (TEnd), 6-min walk test (6MWT), Saint George's Respiratory Questionnaire (SGRQ), and baseline dyspnea (BDI) were assessed prior to and after the training programs (12 weeks). The training modalities showed similar improvements (P > 0.05) in SGRQ-total (ST = 13 +/- 14%; CT = 12 +/- 14%; LGT = 11 +/- 10%), BDI (ST = 1.8 +/- 4; CT = 1.8 +/- 3; LGT = 1 +/- 2), 6MWT (ST = 43 +/- 51 m; CT = 48 +/- 50 m; LGT = 31 +/- 75 m), and TEnd (ST = 11 +/- 20 min; CT = 11 +/- 11 min; LGT = 7 +/- 5 min). In the ST and CT groups, an additional improvement in 1-RM values was shown (P < 0.05) compared to the LGT group (ST = 10 +/- 6 to 57 +/- 36 kg; CT = 6 +/- 2 to 38 +/- 16 kg; LGT = 1 +/- 2 to 16 +/- 12 kg). The addition of strength training to our current training program increased muscle strength; however, it produced no additional improvement in walking endurance, dyspnea or quality of life. A simple combined training program provides benefits without increasing the duration of the training sessions.

Effect of three exercise programs on patients with chronic obstructive pulmonary disease

We compared the effect of three different exercise programs on patients with chronic obstructive pulmonary disease including strength training at 50_80 percent of one-repetition maximum (1-RM) (ST; N = 11), low-intensity general training (LGT; N = 13), or combined training groups (CT; N = 11). Body composition, muscle strength, treadmill endurance test (TEnd), 6-min walk test (6MWT), Saint George's Respiratory Questionnaire (SGRQ), and baseline dyspnea (BDI) were assessed prior to and after the training programs (12 weeks). The training modalities showed similar improvements (P > 0.05) in SGRQ-total (ST = 13 ± 14 percent; CT = 12 ± 14 percent; LGT = 11 ± 10 percent), BDI (ST = 1.8 ± 4; CT = 1.8 ± 3; LGT = 1 ± 2), 6MWT (ST = 43 ± 51 m; CT = 48 ± 50 m; LGT = 31 ± 75 m), and TEnd (ST = 11 ± 20 min; CT = 11 ± 11 min; LGT = 7 ± 5 min). In the ST and CT groups, an additional improvement in 1-RM values was shown (P < 0.05) compared to the LGT group (ST = 10 ± 6 to 57 ± 36 kg; CT = 6 ± 2 to 38 ± 16 kg; LGT = 1 ± 2 to 16 ± 12 kg). The addition of strength training to our current training program increased muscle strength; however, it produced no additional improvement in walking endurance, dyspnea or quality of life. A simple combined training program provides benefits without increasing the duration of the training sessions.

Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients.

Tumour necrosis factor (TNF)-alpha has been found to be increased in malnourished chronic obstructive pulmonary disease (COPD) patients; however, the main cause of this phenomenon remains undetermined. In normal subjects, TNF-alpha production may be induced by dietary energy deprivation. The aim of this study was to investigate if stable COPD patients present alterations of inflammatory mediators after 48 h of dietary energy restriction. Fourteen COPD patients were admitted to the hospital while receiving an experimental diet with an energy content of approximately one-third of their energy needs. Clinical evaluation, nutritional assessment and serum levels of interleukin (IL)-6, TNF-alpha and C-reactive protein, and secretion of TNF-alpha by peripheral blood monocytes were assessed on admission and after the experimental diet. For reference values of the laboratory parameters, blood was collected from 10 healthy, elderly subjects. COPD patients showed significantly higher serum concentrations of IL-6 than control subjects, however, the experimental diet was not associated with statistically significant changes in the inflammatory mediators. The findings of this study, although preliminary because of the limited degree and duration of the energy restriction, suggest that the elevated levels of tumour necrosis factor-alpha, previously described in undernourished or weight-losing chronic obstructive pulmonary disease patients, may not be linked to a decrease of dietary energy intake.

Early rather than delayed administration of lisinopril protects the heart after myocardial infarction in rats.

BACKGROUND: ACE inhibitors have shown beneficial results in several studies after myocardial infarction (MI). However, these studies have shown conflicting results about the ideal starting time of the ACE inhibitors administration after MI and the importance of infarct size. OBJECTIVES: This study was designed to assess the long-term effects of lisinopril on mortality, cardiac function, and ventricular fibrosis after MI, in rats. METHODS: Lisinopril (20 mg/kg/day) was given on day 1 or 21 days after coronary occlusion in small or large infarctions. RESULTS: The mortality rate was reduced by 39 % in early treatment and 30 % in delayed treatment in comparison to the untreated rats. Early treatment reduced cardiac dysfunction in small MIs; however, delayed treatment did not. No statistical difference was observed among the groups for large MIs. No statistical difference was observed among the groups with large or small MIs on myocardial hydroxyproline concentration. CONCLUSIONS: Both early and delayed treatments with lisinopril increased survival. Treatment exerts no marked effects on fibrosis; early treatment has exerted beneficial influences on cardiac function whereas delayed treatment had no consistent effects. The protective effect of lisinopril is detectable only in small (< 40 % of LV) MIs.

Effects of losartan on ventricular remodeling in experimental infarction in rats.

OBJECTIVE: To evaluate the effects of losartan on ventricular remodeling and on survival after myocardial infarction in rats. METHODS: After surgical occlusion of left coronary artery, 84 surviving male Wistar rats were divided into two groups: LO treated with losartan (20mg/kg/day, n=33) and NT (n=51), without medication. After 3 months, we analyzed mortality; ventricular to body mass ratio (VM /BM); myocardial hydroxyproline concentration (HOP); isovolumetric pressure, +dp/dt, -dp/dt, and diastolic volume/left ventricle mass ratio (VO/LV). RESULTS: Mortality was: LO = 22 %, and NT = 47 % (p<0.05). Ventricular mass,(VM/BM, mg/g) was 4.14 +/- 0.76 and 3.54+/-0.48, in the NT and LO groups, respectively (p<0.05). HOP (median) was 4.92 upsilong/mg in the LO and 5.54 upsilong/g in the NT group (p>0.05). The V0/LV values (median) were 0.24 mL/g in group LO and 0.31 mL/g in group NT (p<0.05) compared to NT group. There were no differences between the groups for +dp/dt and -dp/dt parameters. CONCLUSION: 1. The use of losartan myocardial infarction causes an attenuation of ventricular remodeling, bringing about an increased survival, an attenuation of ventricular hypertrophy and dilation, and an improvement of the isovolumetric pressure; 2. the treatment does not modify the myocardial collagen concentration.

Combination therapy with angiotensin converting enzyme inhibition and AT1 receptor inhibitor on ventricular remodeling after myocardial infarction in rats.

BACKGROUND: There are limited data regarding the effects of angiotensin II receptor blockade after myocardial infarction (MI). In addition, whether combined angiotensin converting enzyme (ACE) inhibitor and angiotensin II type I (AT(1)) receptor antagonist may be superior to either drug alone on ventricular remodeling remains unclear. The goal of this study was to determine if the cardiac effects of the combined administration of an ACE inhibitor and AT(1) receptor antagonist are greater than those produced by either of these agents administered individually after MI. METHODS AND RESULTS: After MI, rats were divided into 4 groups: 1) untreated animals, 2) lisinopril treatment (20 mg/kg/day), 3) losartan treatment (20 mg/kg/day), and 4) lisinopril plus losartan treatment. After 3 months, the cardiac parameters studied were: mortality, fibrosis (hydroxyproline), hypertrophy (ventricular weight/body weight ratio [VW/BW]), left ventricular enlargement (volume at end-diastolic pressure equaled zero/body weight ratio [V0/BW]), and ventricular function (isovolumetric developed pressure, dp/dt, -dp/dt). A lowest mortality rate in the animals treated with the combination of both ACE inhibitor and AT(1) receptor antagonist was observed. Although lisinopril and losartan significantly decreased VW/BW ratio, when administered concomitantly, VW/BW ratio was lower than when either agent was administered individually. There were no differences in right ventricle hydroxyproline concentration. Only combination therapy decreased V0/BW ratio. The treatment with lisinopril plus losartan resulted in increases in the development of pressure versus untreated group; without alteration in dp/dt and -dp/dt. CONCLUSIONS: The combination of the AT(1) receptor blockade and ACE inhibitor is more effective than individual treatment on ventricular remodeling and survival after MI in rats.

Beta-carotene and other carotenoids as antioxidants.

Carotenoids are natural pigments which are synthesized by plants and are responsible for the bright colors of various fruits and vegetables. There are several dozen carotenoids in the foods that we eat, and most of these carotenoids have antioxidant activity. Beta-carotene has been best studied since, in most countries it is the most common carotenoid in fruits and vegetables. However, in the U.S., lycopene from tomatoes now is consumed in approximately the same amount as beta-carotene. Antioxidants (including carotenoids) have been studied for their ability to prevent chronic disease. Beta-carotene and others carotenoids have antioxidant properties in vitro and in animal models. Mixtures of carotenoids or associations with others antioxidants (e.g. vitamin E) can increase their activity against free radicals. The use of animals models for studying carotenoids is limited since most of the animals do not absorb or metabolize carotenoids similarly to humans. Epidemiologic studies have shown an inverse relationship between presence of various cancers and dietary carotenoids or blood carotenoid levels. However, three out of four intervention trials using high dose beta-carotene supplements did not show protective effects against cancer or cardiovascular disease. Rather, the high risk population (smokers and asbestos workers) in these intervention trials showed an increase in cancer and angina cases. It appears that carotenoids (including beta-carotene) can promote health when taken at dietary levels, but may have adverse effects when taken in high dose by subjects who smoke or who have been exposed to asbestos. It will be the task of ongoing and future studies to define the populations that can benefit from carotenoids and to define the proper doses, lengths of treatment, and whether mixtures, rather than single carotenoids (e.g. beta-carotene) are more advantageous.

Effects of lisinopril on experimental ischemia in rats. Influence of infarct size.

OBJECTIVE - Angiotensin-converting enzyme inhibitors (ACEIs) have gained importance in preventing or attenuating the process of ventricular remodeling after myocardial infarction. The significance of infarct size in regard to the response to ACEIs, however, is controversial. This study aimed to analyze the effects of lisinopril on mortality rate, cardiac function, degree of cardiac hypertrophy and fibrosis in rats with different infarct sizes. METHODS - Lisinopril (20 mg/kg/day) dissolved in drinking water was administered to rats immediately after coronary artery occlusion. After being sacrificed, the infarcted animals were divided into two groups: one group of animals with small infarcts (< 40% of the left ventricle) and another group of animals with large infarcts (> 40% of the left ventricle). RESULTS - The mortality rate was 31.7% in treated rats and 47% in the untreated rats. There was no statistical difference between the groups with small and large infarcts in regard to myocardial concentration of hydroxyproline. In small infarcts, the treatment attenuated the heart dysfunction characterized by lower levels of blood pressure and lower values of the first derivative of pressure and of the negative derivative of pressure. The degree of hypertrophy was also attenuated in small infarcts. In regard to large infarcts, no differences between the groups were observed. CONCLUSION - Treatment with the ACEIs had no effect on mortality rate and on the amount of fibrosis. The protective effect of lisinopril on heart function and on the degree of hypertrophy could only be detected in small infarcts

Postprandial plasma carotenoid responses following consumption of strawberries, red wine, vitamin C or spinach by elderly women.

This study investigated the postprandial plasma responses of carotenoids for 24 h after feeding five specific breakfast beverages; four of which had low or no carotenoid content. In seven fasting healthy elderly female subjects a blood sample (baseline) was obtained, after which they were given a breakfast beverage, containing one of the following: 1) strawberries (240 g); 2) ascorbic acid (1250 mg); 3) spinach (294 g); 4) red wine (300 mL); and 5) control (breakfast beverage only). Blood samples were collected at 0.5, 1, 4, 7, 11, 15 and 24 h. Plasma carotenoids were measured using HPLC. No significant differences were found in the levels of the plasma carotenoids measured among the various treatments at baseline. In the spinach treatment, plasma lutein, zeaxanthin and beta-carotene levels at 7, 11, 15 and 24 h were significantly higher than those at baseline, as expected. All of the carotenoids measured in the control and vitamin C treatments, at subsequent sampling times were not significantly different from those at baseline. However, for most carotenoids, strawberry and red wine feeding resulted in significantly lower carotenoids values from baseline at 11 and 15 h. Subjects who received a diet with low levels of carotenoids, but whose postprandial plasma levels of carotenoids remain steady, might be explained by a mechanism that promotes secretion of carotenoids into the circulation. Assuming that plasma carotenoids are being used over time, we hypothesize that strawberries and red wine contain some substances that interfere with the secretion of carotenoids into the circulation.

Correlation between carotenoid concentrations in serum and normal breast adipose tissue of women with benign breast tumor or breast cancer.

To evaluate the relationship between carotenoid concentrations in serum and breast tissue, we measured serum carotenoid concentrations and endogenous carotenoid levels in breast adipose tissue of women with benign breast tumor (n = 46) or breast cancer (n = 44). Before extraction, serum was digested with lipase and cholesterol esterase, and breast adipose tissue was saponified. Serum and tissue carotenoids were extracted with ether/hexane and measured by using HPLC with a C30 column. Serum retinoic acid was extracted with chloroform/methanol and measured using HPLC with a C18 column. There were no significant differences in serum carotenoids [lutein, zeaxanthin, cryptoxanthin (both alpha- and beta-), alpha-carotene, all-trans beta-carotene, 13-cis beta-carotene and lycopene], retinoids (retinol, all-trans and 13-cis retinoic acids), and alpha- and gamma- tocopherol concentrations between benign breast tumor patients and breast cancer patients. A substantial amount of 9-cis beta-carotene was present in adipose tissue and was the only carotenoid that had a significantly lower level in benign breast tumor patients than in breast cancer patients. Correlations between carotenoid concentrations in serum and in breast adipose tissue were determined by combining the data of the two groups. Concentrations of the major serum carotenoids except cryptoxanthin showed significant correlations with breast adipose tissue carotenoid levels. When the concentrations of serum carotenoids were adjusted for serum triglycerides or LDL, correlations between serum carotenoid concentrations and breast adipose tissue carotenoid levels markedly increased, including that of cryptoxanthin (P <0. 001). The strong correlation between serum carotenoid concentrations and endogenous breast adipose tissue carotenoid levels indicate that dietary intake influences adipose tissue carotenoid levels as well as serum concentrations, and that adipose tissue is a dynamic reservoir of fat-soluble nutrients.

Interaction between vitamin K nutriture and bacterial overgrowth in hypochlorhydria induced by omeprazole.

Subjects taking a hydrogen pump blocking agent (omeprazole) develop bacterial overgrowth of the small intestine. We tested the hypothesis that this bacterial overgrowth produces menaquinones, which would meet the vitamin requirement in situations of vitamin K deficiency. In a crossover-type design, 13 healthy volunteers eating a phylloquinone-restricted diet for 35 d were randomly assigned to take omeprazole during the first period of study or starting on day 15 until the end of the study. Coagulation times, serum osteocalcin [total osteocalcin and undercarboxylated osteocalcin (ucOC)], plasma phylloquinone, urinary gamma-carboxyglutamic acid, and plasma undercarboxylated prothrombin (PIVKA-II) were measured. Plasma phylloquinone concentrations declined 82% with dietary phylloquinone restriction (P < 0.05) and were not significantly different in the period when the diet was combined with omeprazole treatment (P > 0.05). The mean value for PIVKA-II during the phylloquinone-restricted diet significantly increased 5.7-fold from baseline (P < 0.05); however, the combination of omeprazole treatment and the phylloquinone-restricted diet significantly reduced PIVKA-II values by 21% (P < 0.05) compared with the diet period alone. There were no alterations in total or percentage ucOC concentrations during the phylloquinone-restricted diet or during the period of diet plus omeprazole treatment. Our data support the hypothesis that bacterial overgrowth results in the synthesis and absorption of menaquinones. These menaquinones contribute to vitamin K nutriture during dietary phylloquinone restriction, but not enough to restore normal vitamin K status.

The interaction between vitamin K nutriture and warfarin administration in patients with bacterial overgrowth due to atrophic gastritis.

Atrophic gastritis patients have intestinal bacterial overgrowth which could produce menaquinones. The aim of this study was to evaluate the interaction between a diet low in phylloquinone and minidoses of warfarin in subjects with and without bacterial overgrowth. Subjects with atrophic gastritis (indicated by serum pepsinogen ratio) and healthy volunteers were studied while fed a restrictive phylloquinone diet and while receiving a minidose of warfarin. Coagulation times, serum osteocalcin, serum undercarboxylated osteocalcin, plasma phylloquinone, plasma K-epoxide, plasma undercarboxylated prothrombin (PIVKA)-II and urinary gamma-carboxyglutamic acid (Gla) were measured. At baseline, there were no differences between groups for any variable measured. Comparisons between baseline and post intervention in both groups, showed significant increases in circulating levels of K-epoxide, PIVKA II and undercarboxylated osteocalcin. However, no differences were observed when comparisons were made between groups. Our data do not support the hypothesis that bacterial synthesis of menaquinones in patients with bacterial overgrowth due to atrophic gastritis confers considerable resistance to the effect of warfarin.

[Effect of lisinopril on cardiac parameters and mortality after myocardial infarction in rats]. / Efeito do lisinopril sobre parâmetros cardíacos e mortalidade no infarto experimental em ratos.

PURPOSE: To analyse the effect of early (< 24h) administration of lisinopril on ventricular remodeling and mortality after myocardial infarction (MI) in rats. METHODS: Wistar rats weighing 200-250 g were submitted to ligation of the left coronary artery (LCA) and divided into three groups: SHAM (S, n = 9); infarcted and lisinopril (20mg/kg/day) treated rats (L, n = 38); infarcted and non-treated animals (NT, n = 24). Three months later, the cardiac function was studied in isolated heart preparation according to the Langendorff technique. Starling curves were constructed using fluid injection in the left ventricular balloon, which permitted to alter the diastolic pressure range from 0 to 30mmHg by means of pressure increments of 5mmHg. Body weight (BW), right ventricular weight (RVW), and RVW/BW were also determined. RESULTS: Three months after the surgery, the comparative mortality rate among groups was: S = 0; L = 34.4% and NT = 54.4% (p > 0.05, for L vs NT). In infarctions < 40% of the left ventricle (LV), the RVW/BW relation was S = L < NT (p < 0.05); the left ventricular systolic pressure was S > L > NT (p < 0.05). In infarctions > 40% of LV, the RVW/BW relation was S < L = NT (p < 0.05). For the Starling curves, the results were S > L > NT (p < 0.05). CONCLUSION: In our model lisinopril did not interfere with post-infarction mortality of rats, although decreasing the mortality risk in 49%, in the treated group. The drug also altered the remodeling process, preventing hypertrophy and systolic disfunction after MI, mainly in infarctions < 40% of LV.

Assessment of vitamin A status in chronic obstructive pulmonary disease patients and healthy smokers.

The relation between vitamin A status and the degree of lung airway obstruction was examined in a cross-sectional study of 36 male subjects aged 43-74 y who were assigned to five groups as follows: healthy nonsmokers (n = 7), healthy smokers (n = 7), mild chronic obstructive pulmonary disease (COPD-mild) patients (n = 9), COPD-moderate-severe patients (n = 7), and COPD-moderate-severe patients with exacerbation (+ex; n = 6). Smoking habits, pulmonary function tests, energy-protein status were assessed; serum concentrations of retinyl esters, retinol, retinol binding protein, and transthyretin and relative dose responses were measured. In addition, 12 male smokers aged 45-61 y with mild COPD were randomly assigned to two groups for a longitudinal study: six subjects consumed vitamin A (1000 RE/d; COPD-vitamin A) and six subjects received placebo for 30 d. Lowered serum retinol concentrations were found in the COPD-moderate-severe and COPD-moderate-severe+ex groups. Measurements of vitamin A status in healthy smokers and in COPD-mild patients were not different from those in healthy nonsmokers. The improvement of pulmonary function test results after vitamin A supplementation [mean increase for 1-s forced expiratory volume (FEV1) = 22.9% in the COPD-vitamin A group] may support the assumption of a local (respiratory) vitamin A deficiency in patients with this disease.