COVID-19 and ethnicity: Does reduced responsiveness to glucocorticoids explain the more aggressive nature of disease among minorities?

Marked ethnic variations in complications and mortality have been noted following infection with COVID-19, with Black, Asian, and minority ethnic groups (BAME) being particularly hard hit. We hypothesise that glucocorticoid resistance stemming from several intrinsic reasons such as chronic social stress and lower circulating levels of Vitamin D may contribute to the exaggerated inflammatory response, more severe disease and poorer outcomes observed in BAME.

COVID-19 and ethnicty: Does reduced responsiveness to glucocorticiods explain the more aggressive nature of disease among minorities?

Marked ethnic variations in complications and mortality have been noted following infection with COVID-19, In the United States, the age-adjusted mortality rate among Blacks is 3.8 times, Hispanics 2.5 times, and Asians 1.5 times higher than Whites. In the United Kingdom, the age-adjusted mortality rate among Blacks is 2.9 times, Pakistani and Bangladeshi 2.2 times, and South Indians 1.8 times than that of Whites. One should consider that the increased mortality seen in BAME may be a consequence of impaired glucocorticoid sensitivity stemming from several intrinsic reasons such as chronic social stress and lower circulating levels of Vitamin D. This study aims to evaluate the effect, or lack thereof, of glucocorticoids on Black, Asian and Minority ethnic groups (BAME) when compared to White populations in the setting of COVID-19 treatment.

COVID-19: Social Displacement and Glucocorticoid Resistance

This study aims to evaluate the effect or lack thereof, of glucocorticoids on Black, Asian, and Minority ethnic groups (BAME) when compared to white populations in the setting of COVID-19 treatment

11ß-hydroxysteroid dehydrogenase type-II activity is affected by grapefruit juice and intense muscular work

ABSTRACT Objective The enzymatic activity of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) is key to protecting mineral corticoid receptors from cortisol and has been implicated in blood pressure regulation. Grapefruit juice (GFJ) and acidity are thought to inhibit this enzyme in vitro. This study examines the effect of GFJ and intense exercise on 11β-HSD2 enzyme activity in vivo. Subjects and methods Eighteen subjects ingested GFJ or apple juice (CON) on separate days prior to reporting to the laboratory in a randomized order. Saliva (Sal) samples were obtained at baseline, 15 and 45 minutes post-treadmill stress test; Sal cortisone (E) and cortisol (F) levels were determined, and the Sal cortisone:cortisol (E:F) ratio was used as an index of 11β-HSD2 enzyme activity at rest and after intense muscular work. Results GFJ treatment decreased baseline 11β-HSD2 enzyme activity (44%) and Sal-E (28%) compared to CON (both, p < 0.05). Sal-E (r = 0.61, p < 0.05) and Sal-F (r = 0.66, p < 0.05) were correlated with diastolic blood pressure (DBP) in GFJ-treated individuals. Treadmill stress significantly increased Sal-E and Sal-F but did not alter 11β-HSD2 enzyme activity regardless of treatment. When treatments were examined separately, CON 11β-HSD2 enzyme activity decreased by 36% (p < 0.05) from baseline to 15 post-treadmill exercise. Conclusion Our findings suggest that GFJ and intense muscular work decrease 11β-HSD-2 activity independently, and no additive effect was noted. The association between DBP and the levels of Sal-F and Sal-E during the GFJ trial should be interpreted cautiously and warrants further investigation.

11ß-hydroxysteroid dehydrogenase type-II activity is affected by grapefruit juice and intense muscular work.

OBJECTIVE: The enzymatic activity of 11ß-hydroxysteroid dehydrogenase-2 (11ß-HSD2) is key to protecting mineral corticoid receptors from cortisol and has been implicated in blood pressure regulation. Grapefruit juice (GFJ) and acidity are thought to inhibit this enzyme in vitro. This study examines the effect of GFJ and intense exercise on 11ß-HSD2 enzyme activity in vivo. SUBJECTS AND METHODS: Eighteen subjects ingested GFJ or apple juice (CON) on separate days prior to reporting to the laboratory in a randomized order. Saliva (Sal) samples were obtained at baseline, 15 and 45 minutes post-treadmill stress test; Sal cortisone (E) and cortisol (F) levels were determined, and the Sal cortisone:cortisol (E:F) ratio was used as an index of 11ß-HSD2 enzyme activity at rest and after intense muscular work. RESULTS: GFJ treatment decreased baseline 11ß-HSD2 enzyme activity (44%) and Sal-E (28%) compared to CON (both, p < 0.05). Sal-E (r = 0.61, p < 0.05) and Sal-F (r = 0.66, p < 0.05) were correlated with diastolic blood pressure (DBP) in GFJ-treated individuals. Treadmill stress significantly increased Sal-E and Sal-F but did not alter 11ß-HSD2 enzyme activity regardless of treatment. When treatments were examined separately, CON 11ß-HSD2 enzyme activity decreased by 36% (p < 0.05) from baseline to 15 post-treadmill exercise. CONCLUSION: Our findings suggest that GFJ and intense muscular work decrease 11ß-HSD-2 activity independently, and no additive effect was noted. The association between DBP and the levels of Sal-F and Sal-E during the GFJ trial should be interpreted cautiously and warrants further investigation.

Age, muscle fatigue, and walking endurance in pre-menopausal women.

Aging is associated with loss of endurance; however, aging is also associated with decreased fatigue during maximal isometric contractions. The aims of this study were to examine the relationship between age and walking endurance (WE) and maximal isometric fatigue (MIF) and to determine which metabolic/fitness components explain the expected age effects on WE and MIF. Subjects were 96 pre-menopausal women. Oxygen uptake (walking economy) was assessed during a 3-mph walk; aerobic capacity and WE by progressive treadmill test; knee extension strength by isometric contractions, MIF during a 90-s isometric plantar flexion (muscle metabolism measured by (31)P MRS). Age was related to increased walking economy (low VO(2), r = -0.19, P < 0.03) and muscle metabolic economy (force/ATP, 0.34, P = 0.01), and reduced MIF (-0.26, P < 0.03). However, age was associated with reduced WE (-0.28, P < 0.01). Multiple regression showed that muscle metabolic economy explained the age-related decrease in MIF (partial r for MIF and age -0.13, P = 0.35) whereas walking economy did not explain the age-related decrease in WE (partial r for WE and age -0.25, P < 0.02). Inclusion of VO(2max) and knee endurance strength accounted for the age-related decreased WE (partial r for WE and age = 0.03, P > 0.80). In premenopausal women, age is related to WE and MIF. In addition, these results support the hypothesis that age-related increases in metabolic economy may decrease MIF. However, decreased muscle strength and oxidative capacity are related to WE.

Dietary adherence during weight loss predicts weight regain.

This study examined the relationship between previous dietary adherence during a low-calorie diet weight loss intervention and subsequent weight change during a 2-year follow-up for weight maintenance. One hundred and sixteen healthy, recently weight reduced (lost ~12 kg, BMI 22-25 kg/m2) premenopausal women were studied. Dietary adherence was assessed by doubly labeled water (DLW) and body composition change. Comparisons were made between the upper and lower tertiles for previous dietary adherence and subsequent weight change at 1- and 2-year follow-up. Percent weight regained was significantly lower (30.9 ± 6.7% vs. 66.7 ± 9.4%; P < 0.05) in the upper compared to the lower adherence tertile for previous weight loss dietary adherence (49.9 ± 8.8% vs. 96.8 ± 12.8% P < 0.05) at 1- and 2-year follow-up, respectively. This difference was partly explained by increases in daily activity-related energy expenditure (AEE) (+95 ± 45 kcal/day vs. -44 ± 42 kcal/day, P < 0.05) and lower daily energy intake (2,066 ± 71 kcal/day vs. 2,289 ± 62 kcal/day, P < 0.05) in the higher tertile for previous dietary adherence, compared to the lower. These findings suggest that higher adherence (i.e., higher tertile) to the previous low-calorie diet predicts lower weight regain over 2-year follow-up for weight maintenance, which is explained by lower energy intake and higher physical activity. Finally, how well an individual adheres to a low-calorie diet intervention during weight loss may be a useful tool for identifying individuals who are particularly vulnerable to subsequent weight regain.

Exercise training prevents regain of visceral fat for 1 year following weight loss.

The purpose of this study was to determine what effect aerobic and resistance exercise training has on gain of visceral fat during the year following weight loss. After being randomly assigned to aerobic training, resistance training, or no exercise training, 45 European-American (EA) and 52 African-American (AA) women lost 12.3 +/- 2.5 kg on a 800 kcal/day diet. Computed tomography was used to measure abdominal subcutaneous and visceral adipose tissue, whereas total fat and regional fat (leg, arm, and trunk) were measured by dual energy X-ray absorptiometry after weight loss and 1 year following the weight loss. Because not all the subjects adhered to the 2 time/week 40 min/day exercise training during the 1-year follow-up, subjects were divided into five groups for analysis: aerobic adherers, aerobic nonadherers, resistance adherers, resistance nonadherers, and no exercise. No significant differences were observed between the aerobic training and resistance training adherers for any variable. However, the aerobic (3.1 kg) and resistance (3.9 kg) exercise adherers gained less weight than any of the other three groups (all >6.2 kg). In addition, the two exercise adherence groups did not significantly increase visceral fat (<0.8%) as compared with the 38% increase for the two nonadhering exercise groups and the 25% for the nonexercise group. In conclusion, as little as 80 min/week aerobic or resistance training had modest positive effects on preventing weight regain following a diet-induced weight loss. More importantly, both aerobic and resistance training prevented regain of potentially harmful visceral fat.

Effect of dietary adherence with or without exercise on weight loss: a mechanistic approach to a global problem.

CONTEXT: Weight loss using low-calorie diets produces variable results, presumably due to a wide range of energy deficits and low-dietary adherence. OBJECTIVE: Our objective was to quantify the relationship between dietary adherence, weight loss, and severity of caloric restriction. DESIGN AND SETTING: Participants were randomized to diet only, diet-endurance training, or diet-resistance training until body mass index (BMI) was less than 25 kg/m(2). PARTICIPANTS: Healthy overweight (BMI 27-30) premenopausal women (n = 141) were included in the study. INTERVENTIONS: An 800-kcal/d(-1) diet was provided, and the exercise groups were engaged in three sessions per week. MAIN OUTCOMES: Dietary adherence, calculated from total energy expenditure determined by doubly labeled water measurements and dual-energy x-ray absorptiometry body composition changes, and degree of caloric restriction were determined. RESULTS: All groups had similar weight loss (approximately 12.1 +/- 2.5 kg) and length of time to reach target BMI (approximately 158 +/- 70 d). Caloric restriction averaged 59 +/- 9%, and adherence to diet was 73 +/- 34%. Adherence to diet was inversely associated to days to reach target BMI (r = -0.687; P < 0.01) and caloric restriction (r = -0.349; P < 0.01). Association between adherence to diet and percent weight lost as fat was positive for the diet-endurance training (r = 0.364; P < 0.05) but negatively correlated for the diet-only group (r = -0.387; P < 0.05). CONCLUSIONS: Dietary adherence is strongly associated with rates of weight loss and adversely affected by the severity of caloric restriction. Weight loss programs should consider moderate caloric restriction relative to estimates of energy requirements, rather than generic low-calorie diets.

Translating exercise biology into the Venezuelan medical education and health care system.

In the absence of pharmacological agents, physical exercise was widely used by physicians in the late 19th century to treat a number of maladies. In the 1950's, epidemiological evidence suggested an association between physical activity and health, and increased interest in clinical exercise biology. By the 1990's, sufficient research data was accumulated on the benefits of exercise, such that North American medical associations, government agencies, and the World Health Organization have published guidelines on exercise for public and clinical populations. Despite this, leaders in medical education have remained reluctant to incorporate exercise biology into the core medical curriculum, or to systematically implement it in graduate medical education. This work reviews Venezuelan exercise biology literature, and its medical applications. Venezuelan scientists and clinicians have invested efforts in cardiopulmonary exercise testing, skeletal muscle adaptations to training and exercise cardiovascular pharmacology in patients, sedentary subjects and athletes. It is suggested here, that there is a need to develop education and research programs in basic and clinical exercise biology in the formal training of medical students, physicians in residency programs, and allied health care professionals. Tentative steps to initiate this process are proposed.

Translating exercise biology into the Venezuelan medical education and health care system

En la ausencia de agentes farmacológicos, el ejercicio físico fue ampliamente usado por médicos a finales del siglo 19 para tratar numerosas enfermedades. Durante el siglo 20, en la década de los 50`s, la evidencia epidemiológica ya suger¡a una asociación entre la actividad física y la salud, y comenzaba un incremento en el interés en la biología del ejercicio con aplicación clínica. Ya en la década de los 90`s, suficiente investigación fue acumulada indicando el beneficio del ejercicio, en Norteamérica ya asociaciones de medicina, entes gubernamentales y la Organización Mundial de la Salud publicaron guías sobre ejercicio para poblaciones clínicas y público en general. No obstante de esto, los dirigentes de educación médica han permanecido renuentes a incorporar la biología del ejercicio al pénsum médico curricular, o a implementarlo sistématicamente en la educación médica de postgrado. Este manuscrito revisa la trayectoria de la biología del ejercicio en Venezuela y sus aplicaciones médicas. Científicos y clínicos venezolanos han hecho contribuciones en áreas tales como pruebas de evaluación cardiopulmonar, adaptaciones de músculo esquelético al enfrentamiento físico y en farmacología cardiovascular en ejercicio en pacientes, sujetos sedentarios y atletas. Se sugiere que hay la necesidad de desarrollar programas de educación e investigación en biología del ejercicio con el fín de incorporar estos conocimientos en la formación del estudiante de medicina, médicos residentes y profesionales aleados al sistema de salud. Se propone una serie de pasos tentativos para iniciar este proceso.

Discordant localization of 2-[18F]-fluoro-2-deoxy-D-glucose in 6-[18F]-fluorodopamine- and [(123)I]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites.

BACKGROUND: Although the majority of pheochromocytomas (PHEO) are benign, a subset is malignant. Computed tomography (CT) and magnetic resonance imaging (MRI) localize PHEO with high sensitivity but, because of limited specificity, [(131)I]- or [(123)I]-metaiodobenzylguanidine ([(131)I]- or [(123)I]-MIBG) is often used as a complementary agent. 6-[18F]-fluorodopamine ([18F]-DA) has been developed as a radiopharmaceutical for the targeting of noradrenergic pathways, and has been shown to result in a better detection rate of PHEO sites than MIBG; however, [18F]-DA has shown a lack of accumulation in some patients with metastatic PHEO. METHODS: Five patients with widespread metastatic PHEO who had CT and MRI evidence of metastatic disease (one man and four women; age range, 25-64 years), and who underwent imaging with [(123)I]-MIBG, [18F]-DA and 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG), were evaluated retrospectively. Tomographic imaging was performed and positron emission tomography (PET) images were inspected visually and quantitatively. RESULTS: All five patients had [(123)I]-MIBG scans that grossly underestimated the extent of disease when compared with conventional CT and MRI. All lesions seen on [(123)I]-MIBG scans were detected on [18F]-DA scans, which also detected additional lesions. Nonetheless, [18F]-DA also failed to detect numerous lesions seen on CT and MRI. In all of these cases, [18F]-FDG PET showed lesions that were not detected on either [(123)I]-MIBG or [18F]-DA scans. CONCLUSIONS: When [(123)I]-MIBG or [18F]-DA fails to localize lesions seen on conventional imaging studies, [18F]-FDG may be recommended as an ancillary test for the diagnosis and localization of metastatic PHEO. This is particularly important in patients with aggressive PHEO.