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Metabolic Syndrome-Induced Cardiac FibrosisZibadi, Sherma January 2009 (has links)
Recent studies support the association between metabolic syndrome (MetS), a cluster of cardiovascular risk factors, and diastolic dysfunction. Disproportionate collagen accumulation, particularly cross-linking of collagen, plays a key role in translating interstitial fibrosis into mechanical chamber stiffness and diastolic dysfunction. Characteristic changes in the expression and activity of myocardial lysyl oxidase (LOX), a matrix modifying enzyme that catalyzes cross-linked collagen, are unclear in MetS. We established a diet-induced MetS model to study diastolic dysfunction by treating male C57BL/6 mice a high-fat high-simple carbohydrate (HFHSC) diet for 6 months. Despite blunted gene expression of LOX isoforms, MetS mice demonstrated significant increase in the ratio of protein expression of mature to proenzyme LOX, enhanced LOX activity, and increased cardiac cross-linked collagen compared with controls. This fibrotic response coincided with marked increase in left ventricular end-diastolic pressure and stiffness and impaired diastolic filling pattern. Our data demonstrate that diet-induced MetS alters the remodeling enzyme LOX, thereby increasing the amount of crosslinking and inducing diastolic dysfunction.Furthermore we examined the role of T-lymphocytes in myocardial LOX regulation in diet-induced fibrotic hearts. Female SCID mice which are devoid of functional T-lymphocytes and C57BL/6 mice were treated with HFHSC diet for 12 months. Similar to male C67BL/6, female HFHSC-fed C57BL/6 mice demonstrated significant increase in maturation and catalytic activity of myocardial LOX, cross-linking, ventricular stiffness and diastolic dysfunction. Whereas induction of LOX protein was minimal in SCID mice compared with wild-type counterparts. Correspondingly fibrillar cross-linked collagen formation and diastolic dysfunction were less prominent in SCID mice. Our results suggest a potential role of T-lymphocytes in induction of myocardial stiffness and diastolic dysfunction through modulation of LOX-dependent collagen maturation.Moreover we studied the role of leptin, an adipokine over-produced in MetS with fibrotic effects in non-cardiac tissues, as a key mediator of profibrogenic responses in the heart by administrating leptin to C57BL/6 and leptin-deficient ob/ob mice. With exogenous leptin administration ob/ob mice displayed passive diastolic filling dysfunction that coincided with increase in myocardial collagen compared with ob/ob controls. Our findings suggest profibrotic effects of leptin in the heart, primarily through predominance of collagen synthesis over degradation.
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Cardiovascular dysfunction and specific coping mechanisms in Africans / L. MalanMalan, Leoné January 2005 (has links)
Motivation: Cardiovascular dysfunction and hypertension are some of the leading causes of
morbidity and mortality in the African population. According to the World Health Organisation the
increases in these diseases are escalating in developing countries. Apart from the contributory
role of genetics towards the incidence of hypertension, evidence regarding lifestyle as a
determinant or marker of cardiovascular diseases in this group is not well known. The
interaction of psychological and physiological mechanisms can contribute towards a broader
scope of behavioural physiology in the higher prevalence of hypertension in Africans.
Objectives: The main objective of the research in this thesis was to compare specific coping
mechanisms of Africans with regard to cardiovascular dysfunction.
Methodology: Manuscripts presented in Chapters 3, 4, and 5 made use of the cross-sectional
comparative epidemiological "Transition and Health during Urbanisation in South
Africa" (THUSA) project. The subjects included apparently healthy African men and women,
which were recruited as a convenience sample from the North West Province, South Africa.
Anthropometric measurements were taken and demographic questionnaires completed. An
adapted Setswana COPE questionnaire was used to classify men and women as predominantly
active (AC) or passive (PC) in coping style. Subjects were further subdivided into rural and
urban groups (Manuscript Two), as well as younger (≤ 40) and older (≥ 45) age groups
(Manuscript Three). The General Health Questionnaire (GHQ) was used to measure subjective
perception of health in all three manuscripts. Blood pressure was recorded continuously before
and during application of the handgrip test using the Finapres apparatus. Subjects were
classified as normotensive and hypertensive after blood pressure measurement by the Finapres
and the Riva-Rocci/Korotkoff method. The emphasis in this study was on the cardiovascular
reactivity values. Fasting, resting serum renin activity, cortisol, prolactin, testosterone, high
density lipoprotein, triglycerides, glucose and plasma fibrinogen values were correlated with
cardiovascular and psychological variables. Significant differences between variables were
determined by means of variance analyses (Manuscript One and Two adjusted for age;
Manuscripts One, Two and Three adjusted for resting cardiovascular data). A logistic regression
analysis was performed to determine the most significant determinants of urbanisation. All
THUSA subjects and parents of under-aged adolescents gave informed consent and the study
- was approved by the Ethics Committee of the Potchefstroom University for Christian Higher
Education. The reader is referred to the abstracts at the beginning of each separate manuscript
in Chapters 3 - 5 for a description of the subjects, study design and analytical methods used in
each paper.
Results and conclusions of the individual manuscripts:
Results from the THUSA study showed that PC men and women reported more symptoms
typical of an abnormal psychological and physiological profile than AC men and women. The
PC men, compared to AC men, exhibited a larger vascular reactivity response as well as
larger plasma renin activity. In contrast, the AC women showed a larger non-significant
vascular reactivity response than PC women. All subjects though reacted with increased
vascular reactivity on the stressor. Men with a PC strategy showed enhanced vascular
reactivity, a perception of poorer health and larger stressor plasma renin activity. PC women
reported more depressive symptoms and younger PC women indicated a higher prevalence
of hypertension than younger AC women.
As a follow-up on the first manuscript, the aim was focused mainly on including the
environmental effect, namely urbanisation, as possible explanatory factor for the atypical
physiological AC women’s' coping style. The rural AC subjects indicated more typical active
coping central cardiac responses than rural PC subjects whereas urbanised AC and PC
subjects indicated greater peripheral responses and hypertension prevalence rates. In
addition, the urbanised AC men and women and PC women as opposed to their rural
counterparts indicated symptoms more of a distress situation with increased values of
prolactin and decreased values of testosterone. This was also accompanied by a perception
of poorer health in women. Results of the AC style suggests that the typical physiological
AC stimulation pattern of urbanised subjects and especially the women is dissociated from
the "normal" physiological AC reaction and is now exhibited as a typical PC physiological
stimulation pattern. The greater vascular reactivity, hypertension prevalence, perception of
poorer health and endocrine distressed profile are associated with a PC and dissociated
physiological AC style in an urban context in African men and women. No differences with
regard to resting blood pressure or endocrine values were obtained when the AC and PC
urbanised groups were compared. Africans develop cardiovascular
dysfunction/hypertension during chronic stress or urbanisation. This implies a
dissociation/habituation of physiological systems of African men and women despite having
an active coping strategy. Active coping is, therefore, not necessarily "successful".
Results of the first two manuscripts direct further investigation concerning the effects of
ageing and urbanisation on the development of cardiovascular dysfunction and metabolic
syndrome indicators in gender groups. The second manuscript showed that all rural AC
subjects exhibit a more typical active coping central cardiac response and that rural PC and
all urbanised subjects (AC and PC) exhibit enhanced peripheral vascular responses on the -
handgrip test. Where peripheral vascular responses were more expected from older
individuals in Manuscript Three, the occurrence of this pattern is strengthened in the younger
subjects. The greater fibrinogen values in all younger urbanised women (AC and PC)
compared to rural women further strengthen the risk for the development of cardiovascular
disease. Increased vascular reactivity, abdominal obesity and increased levels of
triglycerides as well as perception of poorer health were apparent in the urbanised AC
women, PC men and women in comparison to their rural counterparts. The typical
physiological AC stimulation pattern of urbanised women is dissociated from the "normal"
physiological AC responses and is now exhibited as a typical PC physiological stimulation
pattern. A typical PC style in older urbanised subjects is implicated in the greater
hypertension prevalence.
To conclude, it seems as if young urbanised Africans, and especially women, exhibit an AC
style behaviourally with a dissociated physiological AC reaction pattern. Physiologically these
women resemble a typical PC physiological cardiovascular and endocrine profile. This typical
PC cardiovascular stimulation pattern is strengthened by a distressed endocrine profile,
significant metabolic syndrome indicators and a 'perception of poorer health. Older PC style
subjects also presented a greater hypertension prevalence. In this study it seems that
cardiovascular changes that appear at a younger age might be influenced by other factors
including urbanisation as a lifestyle factor as well as specific coping styles. Finally, a careful
suggestion is made that specific coping mechanisms could be seen as a possible risk marker in
the development of the metabolic syndrome. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2005.
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Mazu pagal nestumo trukme vaiku augimas iki 6 metu ir ankstyvi metaboliniai pokyciai / Postnatal growth and hormonal status in children born small for gestational ageValūnienė, Margarita 04 May 2009 (has links)
Darbo tikslas Ištirti mažų pagal nėštumo trukmę vaikų postnatalinį augimo pobūdį, hormonų profilį bei nustatyti prenatalinius ir ankstyvuosius postnatalinius veiksnius įtakojančius vaikų augimą ir metabolinius pokyčius iki brendimo Darbo uždaviniai 1. Ištirti mažų pagal nėštumo trukmę vaikų postnatalinio augimo pobūdį pirmaisiais 6 gyvenimo metais, lyginant juos su to paties amžiaus vaikais, gimusiais atitinkančio nėštumo trukmei svorio ir ūgio. 2. Įvertinti tėvų ir naujagimių antropometrinių rodiklių bei hormonų profilio gimimo metu įtaką mažų pagal nėštumo trukmę vaikų augimui nuo gimimo iki 6 metų. 3. 6 metų mažiems ir atitinkantiems nėštumo trukmę vaikams ištirti hormonų profilį (insulinoidinį augimo faktorių–I (IGF–I), IGF–I surišantį baltymą–3 (IGFBP–3) leptiną, adiponektiną), jautrumą insulinui bei lipidų profilį. 4. Nustatyti gimimo svorio ir ankstyvojo postnatalinio augimo įtaką vaikų nutukimo, atsparumo insulinui bei dislipidemijos rizikai iki brendimo. Mažiems pagal nėštumo trukmę vaikams anksti nustatyti pradiniai metaboliniai pakitimai (sumažėjęs jautrumas insulinui, padidėjęs leptino ir sumažėjęs adiponektino kiekis, dislipidemijos požymiai, gliukozės tolerancijos sutrikimas), žemaūgiškumas, polinkis nutukimui gali suteikti savalaikę informaciją bei galimybę pritaikyti ankstyvas profilaktines priemones nutukimui bei 2 tipo cukrinio diabeto, širdies ir kraujagyslių ligų išsivystymui vyresniame amžiuje. / Aim The present study aims to explore the postnatal growth pattern and hormonal profile in small for gestational age children and to identify prenatal and early postnatal risk factors of short stature and postnatal metabolic changes in early prepubertal age. Objectives: 1. To explore the postnatal growth pattern of children born small for gestational age during the first six years of life in comparison with children of appropriate for gestational age birth size. 2. To evaluate the impact of parental axiology, neonatal anthropometry and hormonal status at birth on the early postnatal growth of small for gestational age children. 3. To investigate hormonal profile (insulin like growth factor-1, insulin like growth factor binding protein-3, adiponectin and leptin), insulin sensitivity and lipid profile in six-year-old small and appropriate for gestational age children. 4. To evaluate the influence of birth size and postnatal growth pattern on the risk of obesity, insulin resistance and dyslipidemia in small for gestational age children during the late prepubertal period.
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Measurement of Endogenous and Exogenous Triacylglycerol Kinetics in the fed and fasted state using stable isotopesSun, Feifei January 2008 (has links)
Emerging evidence has shown that an abnormal postprandial accumulation of dietary tat IS atherogenic. The aim of this study is to measure triacylglycerol (TAG) kinetics in endogenous and exogenous lipoproteins in both fed and fasted states using stable isotopes.
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Cardiovascular dysfunction and specific coping mechanisms in Africans / L. MalanMalan, Leoné January 2005 (has links)
Motivation: Cardiovascular dysfunction and hypertension are some of the leading causes of
morbidity and mortality in the African population. According to the World Health Organisation the
increases in these diseases are escalating in developing countries. Apart from the contributory
role of genetics towards the incidence of hypertension, evidence regarding lifestyle as a
determinant or marker of cardiovascular diseases in this group is not well known. The
interaction of psychological and physiological mechanisms can contribute towards a broader
scope of behavioural physiology in the higher prevalence of hypertension in Africans.
Objectives: The main objective of the research in this thesis was to compare specific coping
mechanisms of Africans with regard to cardiovascular dysfunction.
Methodology: Manuscripts presented in Chapters 3, 4, and 5 made use of the cross-sectional
comparative epidemiological "Transition and Health during Urbanisation in South
Africa" (THUSA) project. The subjects included apparently healthy African men and women,
which were recruited as a convenience sample from the North West Province, South Africa.
Anthropometric measurements were taken and demographic questionnaires completed. An
adapted Setswana COPE questionnaire was used to classify men and women as predominantly
active (AC) or passive (PC) in coping style. Subjects were further subdivided into rural and
urban groups (Manuscript Two), as well as younger (≤ 40) and older (≥ 45) age groups
(Manuscript Three). The General Health Questionnaire (GHQ) was used to measure subjective
perception of health in all three manuscripts. Blood pressure was recorded continuously before
and during application of the handgrip test using the Finapres apparatus. Subjects were
classified as normotensive and hypertensive after blood pressure measurement by the Finapres
and the Riva-Rocci/Korotkoff method. The emphasis in this study was on the cardiovascular
reactivity values. Fasting, resting serum renin activity, cortisol, prolactin, testosterone, high
density lipoprotein, triglycerides, glucose and plasma fibrinogen values were correlated with
cardiovascular and psychological variables. Significant differences between variables were
determined by means of variance analyses (Manuscript One and Two adjusted for age;
Manuscripts One, Two and Three adjusted for resting cardiovascular data). A logistic regression
analysis was performed to determine the most significant determinants of urbanisation. All
THUSA subjects and parents of under-aged adolescents gave informed consent and the study
- was approved by the Ethics Committee of the Potchefstroom University for Christian Higher
Education. The reader is referred to the abstracts at the beginning of each separate manuscript
in Chapters 3 - 5 for a description of the subjects, study design and analytical methods used in
each paper.
Results and conclusions of the individual manuscripts:
Results from the THUSA study showed that PC men and women reported more symptoms
typical of an abnormal psychological and physiological profile than AC men and women. The
PC men, compared to AC men, exhibited a larger vascular reactivity response as well as
larger plasma renin activity. In contrast, the AC women showed a larger non-significant
vascular reactivity response than PC women. All subjects though reacted with increased
vascular reactivity on the stressor. Men with a PC strategy showed enhanced vascular
reactivity, a perception of poorer health and larger stressor plasma renin activity. PC women
reported more depressive symptoms and younger PC women indicated a higher prevalence
of hypertension than younger AC women.
As a follow-up on the first manuscript, the aim was focused mainly on including the
environmental effect, namely urbanisation, as possible explanatory factor for the atypical
physiological AC women’s' coping style. The rural AC subjects indicated more typical active
coping central cardiac responses than rural PC subjects whereas urbanised AC and PC
subjects indicated greater peripheral responses and hypertension prevalence rates. In
addition, the urbanised AC men and women and PC women as opposed to their rural
counterparts indicated symptoms more of a distress situation with increased values of
prolactin and decreased values of testosterone. This was also accompanied by a perception
of poorer health in women. Results of the AC style suggests that the typical physiological
AC stimulation pattern of urbanised subjects and especially the women is dissociated from
the "normal" physiological AC reaction and is now exhibited as a typical PC physiological
stimulation pattern. The greater vascular reactivity, hypertension prevalence, perception of
poorer health and endocrine distressed profile are associated with a PC and dissociated
physiological AC style in an urban context in African men and women. No differences with
regard to resting blood pressure or endocrine values were obtained when the AC and PC
urbanised groups were compared. Africans develop cardiovascular
dysfunction/hypertension during chronic stress or urbanisation. This implies a
dissociation/habituation of physiological systems of African men and women despite having
an active coping strategy. Active coping is, therefore, not necessarily "successful".
Results of the first two manuscripts direct further investigation concerning the effects of
ageing and urbanisation on the development of cardiovascular dysfunction and metabolic
syndrome indicators in gender groups. The second manuscript showed that all rural AC
subjects exhibit a more typical active coping central cardiac response and that rural PC and
all urbanised subjects (AC and PC) exhibit enhanced peripheral vascular responses on the -
handgrip test. Where peripheral vascular responses were more expected from older
individuals in Manuscript Three, the occurrence of this pattern is strengthened in the younger
subjects. The greater fibrinogen values in all younger urbanised women (AC and PC)
compared to rural women further strengthen the risk for the development of cardiovascular
disease. Increased vascular reactivity, abdominal obesity and increased levels of
triglycerides as well as perception of poorer health were apparent in the urbanised AC
women, PC men and women in comparison to their rural counterparts. The typical
physiological AC stimulation pattern of urbanised women is dissociated from the "normal"
physiological AC responses and is now exhibited as a typical PC physiological stimulation
pattern. A typical PC style in older urbanised subjects is implicated in the greater
hypertension prevalence.
To conclude, it seems as if young urbanised Africans, and especially women, exhibit an AC
style behaviourally with a dissociated physiological AC reaction pattern. Physiologically these
women resemble a typical PC physiological cardiovascular and endocrine profile. This typical
PC cardiovascular stimulation pattern is strengthened by a distressed endocrine profile,
significant metabolic syndrome indicators and a 'perception of poorer health. Older PC style
subjects also presented a greater hypertension prevalence. In this study it seems that
cardiovascular changes that appear at a younger age might be influenced by other factors
including urbanisation as a lifestyle factor as well as specific coping styles. Finally, a careful
suggestion is made that specific coping mechanisms could be seen as a possible risk marker in
the development of the metabolic syndrome. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2005.
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The effects of a high walnut and unsalted cashew nut diet on the antioxidant status of subjects with diagnosed metabolic syndrome / Lisa DavisDavis, Lisa January 2005 (has links)
Motivation:
Metabolic syndrome is a constellation of risk factors predisposing to coronary heart
disease (CHD) and is classified as a "disease of modern civilization". Characteristics of
the metabolic syndrome include abdominal obesity, increased triacylglycerol (TG)
concentrations, increased small dense low-density lipoprotein(LDL) particles, decreased
high-density lipoprotein cholesterol (HDL-C), hypertension, insulin resistance,
inflammation, glucose intolerance and/or type 2 diabetes mellitus.
Subjects with metabolic syndrome may be susceptible to oxidative stress due to their
prolonged exposure to elevated glucose levels. A variety of natural antioxidants exists
(e.g. glutathione, l3-carotene, vitamin C, polyphenols) that may prevent oxidative damage
to biological structures. Nuts are rich sources of unsaturated fatty acids, protein, fibre,
.micronutrients, phytochemicals and antioxidants. Duet o their high antioxidant content, it
can, therefore, be speculated that nuts may play a role in the prevention of oxidative
stress in subjects with the metabolic syndrome.
Objective:
- To investigate the effect of a high walnut and a high unsalted cashew nut diet on
the antioxidant status of subjects with metabolic syndrome.
Methods:
Sixty eight subjects with diagnosed metabolic syndrome (according to the ATP III
criteria) were recruited to take part in this parallel, randomized, controlled feeding trial.
Subjects were mainly recruited from the North-West University, Potchefstroom Campus
and surrounding areas. After a run-in period of three weeks during which the participants
followed a prudent diet, subjects were randomly divided into three groups receiving
either walnuts or cashew nuts (63- 108g/day)as part of a prudent diet, or continued with
the prudent control diet. The intervention was followed for eight weeks. Fasting blood
samples were taken at the beginning(after the three week run-in period) and at the end of
the intervention. Antioxidant variables including oxygen radical absorbance capacity
(ORAC), reduced glutathione (GSH)/oxidized glutathione (GSSG), diacron reactive
oxygen metabolites (dRom) were measured at the beginning and the end of the
intervention. C-reactive protein (CRP), fibrinogen and plasminogen activator-inhibitor
activity (PAI-1a) were also measured as markers of inflammation. The antioxidant
capacity and the polyphenol content of the diets and the walnuts and cashew nuts were
determined at the end of the intervention.
Results:
A significant decrease in dRom and significant increases in GSSG, the redox status of
glutathione (GSH/GSSG) and ORAC were observed in all three groups from baseline to
end. GSH remained unchanged from baseline to end in all three groups. No significant
differences in changes in dRom (p = 0.92), GSSG (p = 0.99), GSH/GSSG (p = 0.86),
antioxidant capacity (p = 0.10) and GSH (p = 0.34) were observed from baseline to end
between groups.
The total polyphenol content of the walnut and control diets were similar and
significantly higher than the cashew nut diet. The antioxidant capacity of the walnut and
cashew nut diets showed a tendency to be higher than the control diet (p = 0.07 and p =
0.06 respectively). CRP, fibrinogen and PAI-1a concentrations did not differ significantly
between groups.
Conclusion
No significant differences between the groups receiving walnuts, cashew nuts or no nuts
were observed in GSH, GSSG, GSH/GSSG, dRom or ORAC. Therefore, there seems to
be no beneficial effect of the inclusion of walnuts and cashew nuts in the diet on the
antioxidant status of the participants. / Thesis (M.Sc. (Dietetics))--North-West University, Potchefstroom Campus, 2006.
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Possible association between genetic polymorphisms of the adrenergic receptor genes and obesity and hypertension in South African female volunteers / Isabella Elizabeth van LillVan Lill, Isabella Elizabeth January 2006 (has links)
Introduction: Across the world the incidence of the metabolic syndrome increases annually at an alarming rate.
Two conditions associated with this are obesity and hypertension (high blood pressure). Both have
negative health and lifestyle consequences, numerous studies on adrenergic receptor (AR) gene
polymorphisms in various population groups have proved, although not exclusively, that these
polymorphisms may be positively associated with susceptibility to and progression of obesity and
hypertension. The AR encoding genes are attractive targets for such studies because the ARs, as
part of the sympathetic nervous system, perform important functions like vasoconstriction,
vasodilation, lipolysis and influence the heart's contraction. These functions accentuate the
possible role of AR gene polymorphisms in the onset or progression of obesity and hypertension.
Obesity is a health concern especially among black South African women. The prevalence of
obesity (BMI > 30 kg/m2) in the North-West province of South Africa is high: 28.6%. The POWIRS
(Profile of Obese Women with the Insulin Resistance syndrome) study was conducted in 2003 on
102 black South African female volunteers to search for possible associations of the p2-AR
Gln27Glu and p3-AR Trp64Arg polymorphisms with parameters of the carbohydrate and lipid
metabolism, the index of insulin resistance (HOMA-IR), body mass index (BMI) and body fat %
(Schutte et al., 2005). To our knowledge, this was the first study of its kind in South Africa and
which led to this study and dissertation.
Objectives: The objectives of this study were to: • Determine the incidence of the following polymorphisms in (a) 102 black South African female volunteers and calculate the minor allele frequency:
B1-AR: Ser49Gly;
B2-AR: Arg16Gly; (b) 115 white South African female volunteers and calculate the minor allele frequency: B1-AR: Ser49Gly; B2-AR: Arg16Gly; Gln27Glu; B3-AR: Trp64Arg; • identify possible diplotypes and haplotypes in the study groups; • take relevant physiological parameters (measured in the POWIRS studies) into account in the search for possible associations of these polymorphisms, diplotypes and haplotypes with obesity and high blood pressure as characteristics of the metabolic syndrome; • compare the black and the white study groups with regards to the above mentioned objectives. Methods: DNA was isolated from blood spots on Guthrie cards (collected during the POWIRS studies) and
the respective AR gene regions amplified by polymerase chain reaction (PCR). After restriction
enzyme digestion, the DIVA fragments were separated by agarose gel electrophoresis. Genotypic
findings were examined along with measured physiological parameters (measured during the
POWIRS studies) and statistically processed. Area under the curve (AUC) analysis was performed
on parameters measured during the oral glucose tolerance test. Diplotype and haplotype analyses
were also performed on both subject groups.
Results:
The minor allele frequencies for both groups were calculated and compared to that reported in
other published studies. For the black group, the minor allele frequencies were: 84% (B1-AR
Ser49Gly), 16% (B2-AR Gln27Glu), 49% (B2-AR Arg16Gly) and 28% (B3-AR Trp64Arg) and for the
white group: 94%, 46%, 50% and 7% respectively. The AUC differed in almost every instance of
comparison, but was within normal ranges. Only a few significant differences were identified when
the measured physiological parameters were compared between the genotypes, diplotypes and
haplotypes in each group, most of which were found to be within normal ranges. When the two
groups of test subjects were compared, only minimal differences were observed, most of which
were still found to be well within normal ranges.
Conclusions:
Although no associations were identified between the separate investigated AR gene
polymorphisms, diplotypes or haplotypes and obesity and hypertension or high blood pressure,
indications are present that they may act as contributors to risk factors for the onset and
progression of these characteristics of the metabolic syndrome. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007.
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Possible association between genetic polymorphisms of the adrenergic receptor genes and obesity and hypertension in South African female volunteers / Isabella Elizabeth van LillVan Lill, Isabella Elizabeth January 2006 (has links)
Introduction: Across the world the incidence of the metabolic syndrome increases annually at an alarming rate.
Two conditions associated with this are obesity and hypertension (high blood pressure). Both have
negative health and lifestyle consequences, numerous studies on adrenergic receptor (AR) gene
polymorphisms in various population groups have proved, although not exclusively, that these
polymorphisms may be positively associated with susceptibility to and progression of obesity and
hypertension. The AR encoding genes are attractive targets for such studies because the ARs, as
part of the sympathetic nervous system, perform important functions like vasoconstriction,
vasodilation, lipolysis and influence the heart's contraction. These functions accentuate the
possible role of AR gene polymorphisms in the onset or progression of obesity and hypertension.
Obesity is a health concern especially among black South African women. The prevalence of
obesity (BMI > 30 kg/m2) in the North-West province of South Africa is high: 28.6%. The POWIRS
(Profile of Obese Women with the Insulin Resistance syndrome) study was conducted in 2003 on
102 black South African female volunteers to search for possible associations of the p2-AR
Gln27Glu and p3-AR Trp64Arg polymorphisms with parameters of the carbohydrate and lipid
metabolism, the index of insulin resistance (HOMA-IR), body mass index (BMI) and body fat %
(Schutte et al., 2005). To our knowledge, this was the first study of its kind in South Africa and
which led to this study and dissertation.
Objectives: The objectives of this study were to: • Determine the incidence of the following polymorphisms in (a) 102 black South African female volunteers and calculate the minor allele frequency:
B1-AR: Ser49Gly;
B2-AR: Arg16Gly; (b) 115 white South African female volunteers and calculate the minor allele frequency: B1-AR: Ser49Gly; B2-AR: Arg16Gly; Gln27Glu; B3-AR: Trp64Arg; • identify possible diplotypes and haplotypes in the study groups; • take relevant physiological parameters (measured in the POWIRS studies) into account in the search for possible associations of these polymorphisms, diplotypes and haplotypes with obesity and high blood pressure as characteristics of the metabolic syndrome; • compare the black and the white study groups with regards to the above mentioned objectives. Methods: DNA was isolated from blood spots on Guthrie cards (collected during the POWIRS studies) and
the respective AR gene regions amplified by polymerase chain reaction (PCR). After restriction
enzyme digestion, the DIVA fragments were separated by agarose gel electrophoresis. Genotypic
findings were examined along with measured physiological parameters (measured during the
POWIRS studies) and statistically processed. Area under the curve (AUC) analysis was performed
on parameters measured during the oral glucose tolerance test. Diplotype and haplotype analyses
were also performed on both subject groups.
Results:
The minor allele frequencies for both groups were calculated and compared to that reported in
other published studies. For the black group, the minor allele frequencies were: 84% (B1-AR
Ser49Gly), 16% (B2-AR Gln27Glu), 49% (B2-AR Arg16Gly) and 28% (B3-AR Trp64Arg) and for the
white group: 94%, 46%, 50% and 7% respectively. The AUC differed in almost every instance of
comparison, but was within normal ranges. Only a few significant differences were identified when
the measured physiological parameters were compared between the genotypes, diplotypes and
haplotypes in each group, most of which were found to be within normal ranges. When the two
groups of test subjects were compared, only minimal differences were observed, most of which
were still found to be well within normal ranges.
Conclusions:
Although no associations were identified between the separate investigated AR gene
polymorphisms, diplotypes or haplotypes and obesity and hypertension or high blood pressure,
indications are present that they may act as contributors to risk factors for the onset and
progression of these characteristics of the metabolic syndrome. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007.
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Mixture Effects of Environmental ContaminantsLampa, Erik January 2015 (has links)
Chemical exposure in humans rarely consists of a single chemical. The everyday exposure is characterized by thousands of chemicals mainly present at low levels. Despite that fact, risk assessment of chemicals is carried out on a chemical-by-chemical basis although there is a consensus that this view is too simplistic. This thesis aims to validate a statistical method to study the impact of mixtures of contaminants and to use that method to investigate the associations between circulating levels of a large number of environmental contaminants and atherosclerosis and the metabolic syndrome in an elderly population. Contaminants measured in the circulation represented various classes, such as persistent organic pollutants, plastic-associated chemicals and metals. There was little co-variation among the contaminants and only two clusters of PCBs could be discerned. Gradient boosted CARTs were used to assess additive and multiplicative associations between atherosclerosis, as measured by the intima-media thickness (IMT) and the echogenicity of the intima-media complex (IM-GSM), and prevalent metabolic syndrome. Systolic blood pressure was the most important predictor of IMT while the influence of the contaminants was marginal. Three phthalate metabolites; MMP, MEHP and MIBP were strongly related to IM-GSM. A synergistic interaction was found for MMP and MIBP, and a small antagonistic interaction was found for MIBP and MEHP. Associations between the contaminants and prevalent metabolic syndrome were modest, but three pesticides; p,p’-DDE, hexachlorbenzene and trans-nonachlor along with PCBs 118 and 209 and mercury were the strongest predictors of prevalent metabolic syndrome. This thesis concludes that many contaminants need to be measured to get a clear picture of the exposure. Boosted CARTs are useful for uncovering interactions. Multiplicative and/or additive effects of certain contaminant mixtures were found for atherosclerosis or the metabolic syndrome.
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Maternal Dietary Restriction and the Effects of Postweaning Nutrition on Fetal Development, Insulin Signalling, Glucose Metabolism and Body Composition In C57BL/6J MiceChun, Lauren 25 July 2012 (has links)
Mice (C57BL/6J: B6) exposed to maternal dietary restriction (DR) exhibited fetal growth- restriction and as adults develop symptoms of the metabolic syndrome. We aimed to determine the impact of DR on fetal hepatic gluconeogenic pathway and insulin sensitivity in late gestation. Second, we aimed to determine whether a postweaning diet rich in omega-3 fatty acids would alter the development of glucose intolerance, insulin resistance and obesity in DR male offspring. The reduced rate of fetal glycogen synthesis by DR male offspring and altered hepatic gene expression of enzymes involved in insulin signalling and glucose metabolism suggest abnormal fetal development in response to DR that may contribute to the later development of the metabolic syndrome. The postweaning omega-3 diet improved obesity, glucose intolerance and insulin resistance in both DR and control males. These data suggest that nutrition in pregnancy and postnatal life play important roles in determining life-long metabolic health.
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