Are homeopathics able to replace antibiotics in the therapy of bovine mastitis? A placebo controlled randomized double-blind trial

To evaluate the effects of homeopathics on clinical mastitis cows and herd udder health this investigation was conducted in a Brandenburg bio-dyn herd of about 300 cows in two phases using a randomized doubleblind control trial design. After the first part in July 2002 the results preliminarily were evaluated and then the whole concept due to unsatisfying results was adapted. In Phase 1 a number of 121 clinical mastitis cases with 137 affected quarters matched the including criteria, in Phase 2 the number was 126 cows with 148 quarters. These animals were allocated to a code number which classified the case to Verum (n=65 and n=60) or placebo group (n=56 and n=66). In case of clinical mastitis cows were treated either by the oral dilution contending the required combined homeopathics or placebo. Animals were treated twice a day for 5 to 14 days (Phase 2: 1 to 7 days) depending on development of disease. In case of therapy failure in Phase 1 all animals were treated by an not coded homeopathic preparation and in Phase 2 by antibiotics according to bacteriological findings. Milk samples (double samples) for bacteriological and cell count investigation were taken before treatment (M1), 4 to 5 weeks after treatment termination (M2) and 7 to 8 weeks after treatment termination (M3). To evaluate the herd situation additional samples were taken after calving and before dry off. Healing criteria on the cow level was the clinical cure without secondary therapy and release to production. On quarter level the cure was determined by bacterial findings (BCR) and additional by cytological findings. A quarter was determined as „completely cured“, if no bacteria were found AND the cell count was below 100.000/ml. To assess the reduction of antibiotics within the concept it was hypothetically assumed that the mastitis cows had an average milk yield of 20,5 kg per day, was treated under conventional conditions by antibiotics over 3 days with a mean withdrawal time of 5 days (organic conditions x2). Afterwards, these theoretical values were compared to the extrapolated antibiotics input within our concept. Results While there is no difference between the cows in phase 1, on quarter level the verum group showed a significant higher complete cure rate than placebo group in Phase 2. These results are balanced by additional antibiotics treatment in case of therapy failure in the placebo group. The complete cure rate in the verum group after 8 weeks was 32% compared to 13% in placebo group (p<0.05). The limited cure results in single cows did not lead to an udder health depression of the herd. During the study the mean of somatic cell count could decreased by 100.000 cells/ml while the milk yield increased slightly by 250 kg/cow to 6.500 kg/cow/year. The number of actual antibiotic treatments during observation time compared to the number of mastitis cases which would be treated by antibiotics under conventionel conditions showed a reduction by 75%. The extrapolated reduction of milk loss by withdrawal was 25.000kg and the reduction of contaminated milk during treatment time was 13.100 kg per year for the herd. Discussion and Conclusions The increasing cure rates in the second part of the study are influenced by the enhancement of environmental preconditions in combination with the simplified therapy scheme. The therapists seemed to be more familiar with the fixed combinations of homeopathics so that positive effects of the homeopathics can be seen in this phase. After additional antibiotic treatments in case of therapy failure in specific infections (i.e. streptococci and staph. aureus) the cure rates could be elevated to a satisfying level. This fact shows that the limited and controlled use of antibiotics in organic herds can be helpful in the mastitis control. Regardless the conceptual modification to an antibiotic emergency concept, the massive reduction of antibiotics in combination with an increase of herd udder health justifies the therapy protocol in the second phase of the study. Hypothetically, the self cure of the animals is higher than known. The interaction between farmer or therapist and the cow could be a crucial criterion for the positive development of disease. As a conclusion, the integrated system consisting of preventive herd measures and complementary therapy added by limited antibiotic therapy. The precondition for the success is the attendance to optimize environmental conditions. The therapy system should be transparent, simple and easy to use. However, it is necessary to reflect every single mastitis case as a special one

Chronic Activation of Hepatic Nrf2 Has No Major Effect on Fatty Acid and Glucose Metabolism in Adult Mice

The transcription factor NF-E2-related factor 2 (Nrf2) induces cytoprotective genes, but has also been linked to the regulation of hepatic energy metabolism. In order to assess the pharmacological potential of hepatic Nrf2 activation in metabolic disease, Nrf2 was activated over 7 weeks in mice on Western diet using two different siRNAs against kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2. Whole genome expression analysis followed by pathway analysis demonstrated successful knock-down of Keap1 expression and induction of Nrf2-dependent genes involved in anti- oxidative stress defense and biotransformation, proving the activation of Nrf2 by the siRNAs against Keap1. Neither the expression of fatty acid- nor carbohydrate-handling proteins was regulated by Keap1 knock-down. Metabolic profiling of the animals did also not show effects on plasma and hepatic lipids, energy expenditure or glucose tolerance. The data indicate that hepatic Keap1/Nrf2 is not a major regulator of glucose or lipid metabolism in mice

Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study.

AIMS/HYPOTHESIS: The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants associated with insulin resistance and beta cell dysfunction among this population. METHODS: Data from the cross-sectional multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study were analysed. Participants included Ghanaian individuals without diabetes, aged 18-96 years old, who were residing in Amsterdam (n = 1337), Berlin (n = 502), London (n = 961), urban Ghana (n = 1309) and rural Ghana (n = 970). Glucose and insulin were measured in fasting venous blood samples. Anthropometrics were assessed during a physical examination. Questionnaires were used to assess demographics, physical activity, smoking status, alcohol consumption and energy intake. Insulin resistance and beta cell function were determined using homeostatic modelling (HOMA-IR and HOMA-B, respectively). Logistic regression analysis was used to study the contribution of HOMA-IR and inverse HOMA-B (beta cell dysfunction) to geographical differences in IFBG (fasting glucose 5.6-6.9 mmol/l). Multivariate linear regression analysis was used to identify determinants associated with HOMA-IR and inverse HOMA-B. RESULTS: IFBG was more common in individuals residing in urban Ghana (OR 1.41 [95% CI 1.08, 1.84]), Amsterdam (OR 3.44 [95% CI 2.69, 4.39]) and London (OR 1.58 [95% CI 1.20 2.08), but similar in individuals living in Berlin (OR 1.00 [95% CI 0.70, 1.45]), compared with those in rural Ghana (reference population). The attributable risk of IFBG per 1 SD increase in HOMA-IR was 69.3% and in inverse HOMA-B was 11.1%. After adjustment for HOMA-IR, the odds for IFBG reduced to 0.96 (95% CI 0.72, 1.27), 2.52 (95%CI 1.94, 3.26) and 1.02 (95% CI 0.78, 1.38) for individuals in Urban Ghana, Amsterdam and London compared with rural Ghana, respectively. In contrast, adjustment for inverse HOMA-B had very minor impact on the ORs of IFBG. In multivariate analyses, BMI (β = 0.17 [95% CI 0.11, 0.24]) and waist circumference (β = 0.29 [95%CI 0.22, 0.36]) were most strongly associated with higher HOMA-IR, whereas inverse HOMA-B was most strongly associated with age (β = 0.20 [95% CI 0.16, 0.23]) and excess alcohol consumption (β = 0.25 [95% CI 0.07, 0.43]). CONCLUSIONS/INTERPRETATION: Our findings suggest that insulin resistance, rather than beta cell dysfunction, is more important in accounting for the geographical differences in IFBG among sub-Saharan African individuals. We also show that BMI and waist circumference are important factors in insulin resistance in this population

Microvascular and macrovascular complications in type 2 diabetes Ghanaian residents in Ghana and Europe: The RODAM study.

AIMS: To compare microvascular and macrovascular complication rates among Ghanaians with type 2 diabetes (T2D) living in Ghana and in three European cities (Amsterdam, London and Berlin). METHODS: Data from the multicenter Research on Obesity and Diabetes among African Migrants (RODAM) study were analyzed. 650 Ghanaian participants with T2D (206 non-migrant and 444 migrants) were included. Logistic regression analyses were used to determine the association between migrant status and microvascular (nephropathy and retinopathy) and macrovascular (coronary artery disease (CAD), peripheral artery disease (PAD) and stroke) complications with adjustment for age, gender, socioeconomic status, alcohol, smoking, physical activity, hypertension, BMI, total-cholesterol, and HbA1c. RESULTS: Microvascular and macrovascular complications rates were higher in non-migrant Ghanaians than in migrant Ghanaians (nephropathy 32.0% vs. 19.8%; PAD 11.2% vs. 3.4%; CAD 18.4% vs. 8.3%; and stroke 14.5% vs. 5.6%), except for self-reported retinopathy (11.0% vs. 21.6%). Except nephropathy and stroke, the differences persisted after adjustment for the above-mentioned covariates: PAD (OR 7.48; 95% CI, 2.16-25.90); CAD (2.32; 1.09-4.93); and retinopathy (0.23; 0.07-0.75). CONCLUSIONS: Except retinopathy, the rates of microvascular and macrovascular complications were higher in non-migrant than in migrant Ghanaians with T2D. Conventional cardiovascular risk factors did not explain the differences except for nephropathy and stroke

Dietary patterns and type 2 diabetes among Ghanaian migrants in Europe and their compatriots in Ghana: the RODAM study.

BACKGROUND/OBJECTIVES: We aimed to study the associations of dietary patterns (DPs) with type 2 diabetes (T2D) among Ghanaian adults. SUBJECTS/METHODS: In the multi-centre, cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study (n = 4543), three overall DPs ("mixed", "rice, pasta, meat and fish," and "roots, tubers and plantain") and two site-specific DPs per study site (rural Ghana, urban Ghana and Europe) were identified by principal component analysis. The DPs-T2D associations were calculated by logistic regression models. RESULTS: Higher adherence to the "rice, pasta, meat and fish" DP (characterized by legumes, rice/pasta, meat, fish, cakes/sweets, condiments) was associated with decreased odds of T2D, adjusted for socio-demographic factors, total energy intake and adiposity measures (odds ratio (OR)per 1 SD = 0.80; 95% confidence interval (CI) = 0.70-0.92). Similar DPs and T2D associations were discernible in urban Ghana and Europe. In the total study population, neither the "mixed" DP (whole grain cereals, sweet spreads, dairy products, potatoes, vegetables, poultry, coffee/tea, sodas/juices, olive oil) nor the "roots, tubers and plantain" DP (refined cereals, fruits, nuts/seeds, roots/tubers/plantain, fermented maize products, legumes, palm oil, condiments) was associated with T2D. Yet, after the exclusion of individuals with self-reported T2D, the "roots, tubers and plantain" DP was inversely associated with T2D (ORper 1 SD = 0.88; 95% CI = 0.69-1.12). CONCLUSION: In this Ghanaian population, DPs characterized by the intake of legumes, fish, meat and confectionery were inversely associated with T2D. The effect of a traditional-oriented diet (typical staples, vegetables and legumes) remains unclear

Ideal cardiovascular health among Ghanaian populations in three European countries and rural and urban Ghana: the RODAM study.

Cardiovascular health (CVH) is a construct defined by the American Heart Association (AHA) as part of its 2020 Impact Goal definition. CVH has, until now, not been evaluated in Sub-Saharan African populations. The aim of this study was to investigate differences in the prevalence of ideal CVH and its constituent metrics among Ghanaians living in rural and urban Ghana and Ghanaian migrants living in three European countries. The AHA definition of CVH is based on 7 metrics: smoking, body mass index, diet, physical activity, blood pressure, total cholesterol, and fasting plasma glucose. These were evaluated among 3510 Ghanaian adults (aged 25-70 years) residing in rural and urban Ghana and three European cities (Amsterdam, London and Berlin) in the multi-centre RODAM study. Differences between groups were assessed using logistic regression with adjustments for gender, age, and education. Only 0.3% of all participants met all 7 metrics of the AHA's definition of ideal CVH. Compared to rural Ghana (25.7%), the proportions and adjusted odds ratio (OR) of individuals who had 6-7 CVH metrics in the ideal category were substantially lower in urban Ghana, (7.5%; OR 0.204, 95% CI 0.15-0.29), Amsterdam (4.4%; 0.13, 0.08-0.19), Berlin (2.7%; 0.06, 0.03-0.11), and London (1.7%; 0.04, 0.02-0.09), respectively. The proportion of ideal CVH for the various metrics ranged from 96% for all sites in the smoking metric to below 6% in the diet metric. The proportion of ideal CVH is extremely low in Ghanaians, especially among those living in urban Ghana and Ghanaian migrants in Europe

Cardiovascular disease risk prediction in sub-Saharan African populations - Comparative analysis of risk algorithms in the RODAM study.

BACKGROUND: Validated absolute risk equations are currently recommended as the basis of cardiovascular disease (CVD) risk stratification in prevention and control strategies. However, there is no consensus on appropriate equations for sub-Saharan African populations. We assessed agreement between different cardiovascular risk equations among Ghanaian migrant and home populations with no overt CVD. METHODS: The 10-year CVD risks were calculated for 3586 participants aged 40-70years in the multi-centre RODAM study among Ghanaians residing in Ghana and Europe using the Framingham laboratory and non-laboratory and Pooled Cohort Equations (PCE) algorithms. Participants were classified as low, moderate or high risk, corresponding to 20% respectively. Agreement between the risk algorithms was assessed using kappa and correlation coefficients. RESULTS: 19.4%, 12.3% and 5.8% were ranked as high 10-year CVD risk by Framingham non-laboratory, Framingham laboratory and PCE, respectively. The median (25th-75th percentiles) estimated 10-year CVD risk was 9.5% (5.4-15.7), 7.3% (3.9-13.2) and 5.0% (2.3-9.7) for Framingham non-laboratory, Framingham laboratory and PCE, respectively. The concordance between PCE and Framingham non-laboratory was better in the home Ghanaian population (kappa=0.42, r=0.738) than the migrant population (kappa=0.24, r=0.732) whereas concordance between PCE and Framingham laboratory was better in migrant Ghanaians (kappa=0.54, r=0.769) than the home population (kappa=0.51, r=0.758). CONCLUSION: CVD prediction with the same algorithm differs for the migrant and home populations and the interchangeability of Framingham laboratory and non-laboratory algorithms is limited. Validation against CVD outcomes is needed to inform appropriate selection of risk algorithms for use in African ancestry populations

Food variety, dietary diversity, and type 2 diabetes in a multi-center cross-sectional study among Ghanaian migrants in Europe and their compatriots in Ghana: the RODAM study.

PURPOSE: The importance of dietary diversification for type 2 diabetes (T2D) risk remains controversial. We investigated associations of between- and within-food group variety with T2D, and the role of dietary diversification for the relationships between previously identified dietary patterns (DPs) and T2D among Ghanaian adults. METHODS: In the multi-center cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) Study (n = 3810; Ghanaian residence, 56%; mean age, 46.2 years; women, 63%), we constructed the Food Variety Score (FVS; 0-20 points), the Dietary Diversity Score (DDS; 0-7 points), and the Diet Quality Index-International (DQI-I) variety component (0-20 points). The associations of these scores, of a "rice, pasta, meat and fish" DP, of a "mixed" DP, and of a "roots, tubers and plantain" DP with T2D were calculated by logistic regression. RESULTS: The FVS was inversely associated with T2D, adjusted for socio-demographic, lifestyle, and anthropometric factors [odds ratio (OR) for T2D per 1 standard deviation (SD) increase: 0.81; 95% confidence interval (CI) 0.71-0.93]. The DDS and the DQI-I variety component were not associated with T2D. There was no association of the "mixed" DP and the "roots, tubers and plantain" DP with T2D. Yet, the "rice, pasta, meat and fish" DP is inversely associated with T2D (OR for T2D per 1 SD increase: 0.82; 95% CI 0.71-0.95); this effect was slightly attenuated by the FVS. CONCLUSIONS: In this Ghanaian population, between-food group variety may exert beneficial effects on glucose metabolism and partially explains the inverse association of the "rice, pasta, meat and fish" DP with T2D

Obesity and type 2 diabetes in sub-Saharan Africans - Is the burden in today's Africa similar to African migrants in Europe? The RODAM study.

BACKGROUND: Rising rates of obesity and type 2 diabetes (T2D) are impending major threats to the health of African populations, but the extent to which they differ between rural and urban settings in Africa and upon migration to Europe is unknown. We assessed the burden of obesity and T2D among Ghanaians living in rural and urban Ghana and Ghanaian migrants living in different European countries. METHODS: A multi-centre cross-sectional study was conducted among Ghanaian adults (n = 5659) aged 25-70 years residing in rural and urban Ghana and three European cities (Amsterdam, London and Berlin). Comparisons between groups were made using prevalence ratios (PRs) with adjustments for age and education. RESULTS: In rural Ghana, the prevalence of obesity was 1.3 % in men and 8.3 % in women. The prevalence was considerably higher in urban Ghana (men, 6.9 %; PR: 5.26, 95 % CI, 2.04-13.57; women, 33.9 %; PR: 4.11, 3.13-5.40) and even more so in Europe, especially in London (men, 21.4 %; PR: 15.04, 5.98-37.84; women, 54.2 %; PR: 6.63, 5.04-8.72). The prevalence of T2D was low at 3.6 % and 5.5 % in rural Ghanaian men and women, and increased in urban Ghanaians (men, 10.3 %; PR: 3.06; 1.73-5.40; women, 9.2 %; PR: 1.81, 1.25-2.64) and highest in Berlin (men, 15.3 %; PR: 4.47; 2.50-7.98; women, 10.2 %; PR: 2.21, 1.30-3.75). Impaired fasting glycaemia prevalence was comparatively higher only in Amsterdam, and in London, men compared with rural Ghana. CONCLUSION: Our study shows high risks of obesity and T2D among sub-Saharan African populations living in Europe. In Ghana, similarly high prevalence rates were seen in an urban environment, whereas in rural areas, the prevalence of obesity among women is already remarkable. Similar processes underlying the high burden of obesity and T2D following migration may also be at play in sub-Saharan Africa as a consequence of urbanisation

Early-life factors are associated with waist circumference and type 2 diabetes among Ghanaian adults: The RODAM Study.

Early-life experiences may fuel the emergence of obesity and type 2 diabetes among African populations. We evaluated childhood socio-economic status (SES) and childhood nutritional status as risk factors for increased waist circumference and type 2 diabetes among Ghanaian adults. In the multi-center, cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) Study, we calculated associations (adjusted for demographics and lifestyle) of parental education and anthropometric markers of childhood nutrition [leg length, leg length-to-height ratio (LHR)] with waist circumference and type 2 diabetes, respectively. Among 5,575 participants (mean age: 46.2 years; 62% female), lower education of either parent (vs. higher) was consistently associated with higher waist circumference (∆: 1.6-3.4 cm). Lower father's education tended to increase the odds of type 2 diabetes by 50% in women (95% confidence interval (CI): 1.0, 2.4). Reduced leg length and LHR were associated with higher waist circumference. But only in men, leg length was inversely related to type 2 diabetes (OR per 1 standard deviation decrease: 1.1; 95% CI: 1.0, 1.3). In this study, markers of poor childhood SES and early-life nutritional status relate to abdominal obesity in men and women and to type 2 diabetes in men. Thus, prevention efforts should start in early childhood