Pathophysiological significance of Stim1 mutation in sympathetic response to stress and cardiovascular phenotypes in SHRSP/Izm: In vivo evaluation by creation of a novel gene knock-in rat using CRISPR/Cas9.

Genetic approach using rat congenic lines between SHRSP/Izm and WKY/Izm identified stromal interaction molecule 1 (Stim1), an essential component of store-operated Ca2+ entry (SOCE), as a promising candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP. Since SHRSP has a nonsense mutation in Stim1 resulting in the expression of a truncated form of STIM1 that caused reduction of SOCE activity in primary cultured cerebral astrocytes, we created SHRSP/Izm knocked-in with the wild-type Stim1 (KI SHRSP) by the CRISPR/Cas9 method to investigate whether the functional recovery of STIM1 would mitigate sympatho-excitation to stress in vivo in SHRSP. No potential off-target nucleotide substitutions/deletions/insertions were found in KI SHRSP. Western blotting and fluorescent Ca2+ imaging of astrocytes confirmed wild-type STIM1 expression and restored SOCE activity in astrocytes from KI SHRSP, respectively. Blood pressure (BP) measured by the tail-cuff method at 12, 16, and 20 weeks of age did not significantly differ between SHRSP and KI SHRSP, while the heart rate of KI SHRSP at 16 and 20 weeks of age was significantly lower than that of age-matched SHRSP. Unexpectedly, the sympathetic response to stress (evaluated with urinary excretion of norepinephrine under cold stress and BP elevation under cold/restraint stress) did not significantly differ between SHRSP and KI SHRSP. The present results indicated that the functional deficit of STIM1 was not a genetic determinant of the exaggerated sympathetic response to stress in SHRSP and that it would be necessary to explore other candidates within the congenic fragment on chromosome 1.

Elevated blood pressure among primary school children in Dar es salaam, Tanzania: prevalence and risk factors.

BACKGROUND: Whilst the burden of non-communicable diseases is increasing in developing countries, little data is available on blood pressure among Tanzanian children. This study aimed at determining the blood pressure profiles and risk factors associated with elevated blood pressure among primary school children in Dar es Salaam, Tanzania. METHODS: We conducted a cross sectional survey among 446 children aged 6-17 years from 9 randomly selected primary schools in Dar es Salaam. We measured blood pressure using a standardized digital blood pressure measuring machine (Omron Digital HEM-907, Tokyo, Japan). We used an average of the three blood pressure readings for analysis. Elevated blood pressure was defined as average systolic or diastolic blood pressure ≥ 90th percentile for age, gender and height. RESULTS: The proportion of children with elevated blood pressure was 15.2% (pre-hypertension 4.4% and hypertension 10.8%). No significant gender differences were observed in the prevalence of elevated BP. Increasing age and overweight/obese children were significantly associated with elevated BP (p = 0.0029 and p < 0.0001) respectively. Similar associations were observed for age and overweight/obesity with hypertension. (p = 0.0506 and p < 0.0001) respectively. In multivariate analysis, age above 10 years (adjusted RR = 3.63, 95% CI = 1.03-7.82) was significantly and independently associated with elevated BP in this population of school age children. CONCLUSIONS: We observed a higher proportion of elevated BP in this population of school age children. Older age and overweight/obesity were associated with elevated BP. Assessment of BP and BMI should be incorporated in school health program in Tanzania to identify those at risk so that appropriate interventions can be instituted before development of associated complications.

Dual inhibition of NADPH oxidases and xanthine oxidase potently prevents salt-induced stroke in stroke-prone spontaneously hypertensive rats.

Oxidative stress has been implicated in the pathophysiology of cerebral stroke. As NADPH oxidases (NOXs) play major roles in the regulation of oxidative stress, we hypothesized that reduction of NOX activity by depletion of p22phox, an essential subunit of NOX complexes, would prevent cerebral stroke. To investigate this, we used the stroke-prone spontaneously hypertensive rat (SHRSP) and the p22phox-deleted congenic SHRSP. Although p22phox depletion reduced blood pressure under salt loading, it did not ameliorate oxidative stress or reduce the incidence of salt-induced stroke in SHRSPs. Additional pharmacological reduction of oxidative stress using antioxidant reagents with different mechanisms of action was necessary to prevent stroke, indicating that NOX was not the major target in salt-induced stroke in SHRSPs. On the other hand, oxidative stress measured based on urinary isoprostane levels showed significant correlations with blood pressure, stroke latency and urinary protein excretion under salt loading, suggesting an important role of oxidative stress per se in hypertension and hypertensive organ damage. Overall, our results imply that oxidative stress from multiple sources influences stroke susceptibility and other hypertensive disorders in salt-loaded SHRSPs.

Evaluation of Pathological Association between Stroke-Related QTL and Salt-Induced Renal Injury in Stroke-Prone Spontaneously Hypertensive Rat.

The stroke-prone spontaneously hypertensive rat (SHRSP) suffers from severe hypertension and hypertensive organ damage such as cerebral stroke and kidney injury under salt-loading. By a quantitative trait locus (QTL) analysis between SHRSP and SHR (the stroke-resistant parental strain of SHRSP), two major QTLs for stroke susceptibility were identified on chromosomes 1 and 18 of SHRSP, which were confirmed in congenic strains constructed between SHRSP and SHR. As the progression of renal dysfunction was suggested to be one of the key factors inducing stroke in SHRSP, we examined effects of the stroke-related QTLs on kidney injury using two congenic strains harboring either of SHRSP-derived fragments of chromosomes 1 and 18 in the SHR genome. The congenic strains were challenged with 1% NaCl solution for 4 weeks; measurement of systolic blood pressure and urinary isoprostane level (a marker for oxidative stress) and evaluation of renal injury by quantification of genetic marker expression and histological examination were performed. We found that the congenic rats with SHRSP-derived fragment of chromosome 18 showed more severe renal damage with higher expression of Col1α-1 (a genetic marker for renal fibrosis) and higher urinary isoprostane level. In contrast, the fragment of chromosome 1 from SHRSP did not give such effects on SHR. Blood pressure was not greater in either of the congenic strains when compared with SHR. We concluded that the QTL region on chromosome 18 might deteriorate salt-induced renal injury in SHR through a blood pressure-independent mechanism.

Knowledge and attitudes towards obesity among primary school children in Dar es Salaam, Tanzania.

BACKGROUND: Childhood obesity has increased over the past two decades. Child obesity is likely to persist through adulthood and increases the risk of non-communicable diseases (NCDs) later in life. This study assessed knowledge and attitudes towards obesity among primary school children in Dar es Salaam, Tanzania. MATERIALS AND METHODS: A cross-sectional study was conducted in randomly selected primary schools in Dar es Salaam. A structured questionnaire was used to assess the knowledge and attitudes. Anthropometric and blood pressure measurements were taken using standard procedures. RESULTS: A total of 446 children were included in the analysis. The mean age of the participants was 11.1 ± 2.0 years. The mean body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 16.6 ± 4.0 kg/m(2), 103.9 ± 10.3 mmHg and 65.6 ± 8.2 mmHg, respectively. Prevalence of obesity (defined as BMI >95(th) percentile for age and sex) was 5.2%. Half of the children (51.1%) had heard about obesity from teachers at school (20%), radio (19.4%) and books/newspaper (17.3%). Less than half (45.4%) had knowledge about the risk factors for childhood obesity and correctly defined obesity (44.6%). However, a good number of the children (72.1%) were aware that they can be affected by obesity. Majority of them had negative attitude towards obesity and various factors leading to or resulting from childhood obesity. CONCLUSIONS: Knowledge about childhood obesity among primary school children is moderate and have negative attitude towards obesity. Integrating educational programs early in primary schools may be an effective strategy to impact knowledge about obesity and other non-communicable diseases early in childhood.

Profile of plasma lipids and degree of derangements among the elderly of Morogoro region, Tanzania.

Changes in lifestyles and ageing have been associated with growing rates of modifiable cardiovascular risk factors (CRF). Dyslipidemia is one ofthe CRF associated with numbers of cardiovascular diseases. This descriptive cross-sectional study was conducted to determine the profile and degree of derangements of plasma lipids among 300 (176 females and 124 males) elderly individuals aged ≥ 60 years in Morogoro, Tanzania. The calorimetric enzymatic methods and the Friedewal's equation were used for determination of cholesterols and triglycerides (TG). Social and demographic characteristics were gathered by structured questionnaires. The logistic regression models were used to identify the determinants of abnormal serum lipids level. Mean Total Cholesterols (TC) and Low Density Lipoprotein Cholesterols (LDL-C) in females exceeded significantly that of males. Mean TC, LDL-C as well as TG (mg/dL) declined significantly with age while mean High Density Lipoprotein Cholesterols (HDL-C) also declined but only slightly. Elderly females were two times more likely to have elevated TC (OR = 2.11; 95% CI: 1.04-4.28: P = 0.05) and LDL-C (OR = 2.15; 95% CI: 1.17- 3.97: P = 0.019) and three times to have lowered HDL-C (OR = 3; 95% CI: 1.97-5.30: P < 0.001) than males. Urban residents were about two times more likely to have elevated LDL-C (OR = 1.84; 95% CI: 1.04-3.25: P = 0.047) than their rural counterparts. Body Mass Index of ≥ 30 kg/m2 was also associated with elevated LDL-C (OR = 1.89; 95% CI: 1.05-3.42: P = 0.045) and lowered HDL-C (OR = 2.18; 95% CI: 1.3-3.65: P = 0.004), respectively. The present study has established the profile and level of derangements of serum lipids among the elderly of Morogoro region in Tanzania. It appears that, female sex and BMI of ≥ 30 kg/m2 are significant factors for elevated TC, LDL-C and lowered HDL-C while urban life is a significant factor for elevated LDL-C.

Overweight, obesity and perceptions about body weight among primary schoolchildren in Dar es Salaam, Tanzania.

The increasing prevalence of overweight and obesity among children has become a public health concern both in developing and developed countries. Previous research studies have shown that favourable perception of one's body weight is an important factor in weight control. This study determined prevalence of overweight and obesity and assessed perception about body weight among primary schoolchildren in Dar es Salaam, Tanzania. In this cross sectional study, nine schools were selected randomly from a list of all primary schools in Dar es Salaam. A structured questionnaire was used to collect data on socio-demographic characteristics and lifestyle information including perception about body weight. Height and weight were measured following standard procedures. Chi- square tests and multiple logistic regressions were used to determine factors which influence perceptions about body weight. A total of 446 children were included into the study. The mean body mass index (BMI) was 16.6 ± 4.0 kg/m2 (16.1 ± 4.0 for males and 17.0 ± 4.0 for females). Prevalence of overweight and obesity was 9.8% and 5.2%, respectively. The prevalence of overweight and obesity was significantly higher among girls, 13.1% and 6.3% compared to boys with 6.3% and 3.8% overweight and obese respectively (P=0.0314). Overall, the prevalence of overweight and obesity was 15.0% (10.1% among boys and 19.4% among girls). One-third (33.3%) of the children perceived their body weight as overweight or obese. Among overweight and obese children, 35.4% had unfavourable perception of their body weights. There was a statistically significant difference between perceived body weight and actual body weight as indicated by BMI for both boys and girls (P < 0.05). Age of the child (AOR = 0.55 95% CI 0.36-0.85) and area of residence (COR = 0.64 95% CI 0.44-0.95) were found to be significant predictors of favourable perception of one's body weight. In conclusion, the prevalence of overweight and obesity is not very high in this population. However over a third of overweight and obese children, had unfavourable perception of their body weights. We recommend targeted educational programmes about overweight and obesity and the associated health effects in order to instil a behaviour of self consciousness on overweight and obesity among children in Tanzania.

Prevalence and determinants of obesity among primary school children in Dar es Salaam, Tanzania.

BACKGROUND: Childhood obesity has increased dramatically and has become a public health concern worldwide. Childhood obesity is likely to persist through adulthood and may lead to early onset of NCDs. However, there is paucity of data on obesity among primary school children in Tanzania. This study assessed the prevalence and determinants of obesity among primary school children in Dar es Salaam. METHODS: A cross sectional study was conducted among school age children in randomly selected schools in Dar es Salaam. Anthropometric and blood pressure measurements were taken using standard procedures. Body Mass Index (BMI) was calculated as weight in kilograms divided by the square of height in meters (kg/m2). Child obesity was defined as BMI at or above 95th percentile for age and sex. Socio-demographic characteristics of children were determined using a structured questionnaire. Logistic regression was used to determine association between independent variables with obesity among primary school children in Dar es Salaam. RESULTS: A total of 446 children were included in the analysis. The mean age of the participants was 11.1±2.0 years and 53.1% were girls. The mean BMI, SBP and DBP were 16.6±4.0 kg/m2, 103.9±10.3mmHg and 65.6±8.2mmHg respectively. The overall prevalence of child obesity was 5.2% and was higher among girls (6.3%) compared to boys (3.8%). Obese children had significantly higher mean values for age (p=0.042), systolic and diastolic blood pressures (all p<0.001). Most obese children were from households with fewer children (p=0.019) and residing in urban areas (p=0.002). Controlling for other variables, age above 10 years (AOR=3.3, 95% CI=1.5-7.2), female sex (AOR=2.6, 95% CI=1.4-4.9), urban residence (AOR=2.5, 95% CI=1.2-5.3) and having money to spend at school (AOR=2.6, 95% CI=1.4-4.8) were significantly associated with child obesity. CONCLUSIONS: The prevalence of childhood obesity in this population was found to be low. However, children from urban schools and girls were proportionately more obese compared to their counterparts. Primary preventive measures for childhood obesity should start early in childhood and address socioeconomic factors of parents contributing to childhood obesity.