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Mechanisms of gestational diabetes mellitus using rat model
No full textPhD ThesisGestational diabetes mellitus (GDM) is a form of
hyperglycemia due to carbohydrate intolerance that begins
during pregnancy. This may be due to insulin resistance or
impairment of insulin secretion during pregnancy.
Knowledge on the pathophysiology of GDM is important for
its management. Thus, the main objective of the current
study was to explore the mechanisms of GDM development
due to high fat diet (HFD) or heat stress (HST) in a rat model.
Specifically, the study was done to evaluate the role of
differential adipose tissue (AT) expansion, influence of
oxidative stress (OS) and to determine the role of placental
cytokine (tumour necrosis factor-alpha (TNF-α) and
interleukin-6 (IL-6)) in the development of GDM.
The study used Wistar rats as experimental animals. Rats of
8 - 10 weeks old were used and experiments were
conducted at the Small Animal Research Unit (SARU),
College of Veterinary Medicine and Biomedical Science
(CVMBS), Sokoine University of Agriculture (SUA),
Morogoro, Tanzania. Samples were analysed in research
laboratories in the Departments of Physiology, Biochemistry
and Pharmacology and Veterinary Anatomy and Pathology.
This thesis is divided into three chapters. Chapter one is on
introduction and literature review. It includes a general
introduction, animal models for GDM, factors governing the
development of GDM, establishing GDM models,
histopathology of pancreas during GDM, placenta and GDM,
objectives of the study, and organization of the thesis.
Chapter two comprises three manuscripts describing the
research findings. The first manuscript describes the
contribution of HFD to the development of GDM. The second
manuscript is on evaluation of how OS due to HST
predisposes rats to GDM. Findings on assessment of theiv
role of placental cytokines (TNF-α and IL-6) in the
development of GDM are presented and discussed in the
third manuscript. Lastly, general discussion, conclusion and
recommendations of the study are provided in chapter three.
Work described in the first manuscript evaluated contribution
of HFD in differential AT expansion and subsequent
development of GDM in Wistar rats. Pregnant and non-
pregnant rats were given streptozotocin (STZ) by a single
intraperitoneal injection or HFD throughout the experiment.
The animals were sacrificed by a combination of ketamine
50 mg/kg and xylazine 5 mg/kg on days 1, 8, 15, and 21 of
the experiment. Blood, AT (both visceral (VAT) and
subcutaneous (SAT)) and pancreas were collected and
analysed. In this study, STZ-treated animals had a
significant increase (p<0.05) in serum glucose and a
decrease in insulin, without changes in the size of
adipocytes. The levels of both serum glucose and insulin
were significantly high in HFD-fed animals (p<0.05); being
higher in pregnant (p<0.05) than non-pregnant rats. The
increase in glucose and insulin levels was associated with
an increase in the size (hypertrophy) than the number
(hyperplasia) of adipocytes. The increase in adipocytes was
higher in VAT and corresponded to insulin resistance and
GDM development than in SAT. Histologically, β-cells were
decreased in number and deformed in STZ groups while
maintained in HFD groups in both pregnant and non-
pregnant animals. This study concluded that intake of HFD
during pregnancy leads to AT expansion, which is one of the
risk factors for the hyperglycemia and development of GDM.
This study demonstrates in the second manuscript the
association between HST and GDM. Pregnant and non-
pregnant Wistar rats were maintained at 41 - 42°C for 21
days. On days 1, 8, 15 and 21 the animals were humanely
sacrificed by a combination of ketamine 50 mg/kg andv
xylazine 5 mg/kg. Blood samples were collected from the
heart for glucose, insulin, malondialdehyde (MDA) and
glutathione peroxidase (GPx) analyses. Pancreatic tissues
were fixed in neutral buffered formalin, and processed for
histopathology. The findings demonstrated that, in pregnant
rats, HST induced a significant increase in glucose in
conjunction with a drop in insulin levels than non-pregnant
rats (p<0.05). In addition, heat treatment was accompanied
by an increase in MDA and a drop in GPx levels. Histological
examinations of the pancreas revealed damaged β-cells
from day 15 and a reduction in the number of β-cells by day
21 of the experiment in pregnant rats. These results suggest
that HST raises the levels of OS in pregnant rats more than
in non-pregnant rats and increases the chances of GDM as
it is associated with β-cell defects in the pancreas.
Findings on serum concentration and placental production of
TNF-α and IL-6 of HFD-given rats during pregnancy and
their correlation with the development of GDM are presented
and discussed in the third manuscript. Pregnant and non-
pregnant rats were given STZ single IP injection or HFD
throughout the experiment. On days 1, 8, 15 and 21, the
animals were humanely sacrificed by a combination of
ketamine 50 mg/kg and xylazine 5 mg/kg. Blood samples
were collected from the heart for glucose, insulin, TNF-α and
IL-6 analyses. Placenta samples were dissected, fixed in
neutral
buffered
formalin,
and
processed
for
histopathological and immunohistochemical analyses for
TNF-α and IL-6. The levels of serum glucose and insulin
were significantly high in HFD-fed animals (p<0.05); being
higher in pregnant (p<0.05) than non-pregnant rats. The
increase in glucose and insulin levels was associated with
an increase in serum levels of TNF-α and IL-6; which were
higher in HFD pregnant than non-pregnant animals on day
21 of the experiment. Histologically, placenta tissues of STZ-
treated animals were severely congested with blood vesselsvi
on days 15 and 21 compared with those from HFD-fed rats
which had low congestion on day 21. In both pregnant and
non-pregnant rats, immunostaining intensity for TNF-α and
IL-6 was high in HFD and STZ-treated animals on day 15
and 21. The findings of this study show that intake of HFD
during pregnancy leads to an increase in the levels of IL-6
and TNF-α in the placenta towards the end of gestation
resulting in insulin resistance and hyperglycemia that may
predispose to GDM.
Therefore, Intake of HFD during pregnancy causes AT
expansion as well as increase in the levels of placental
cytokines (TNF-α and IL-6) resulting in insulin resistance and
hyperglycemia, which are risk factors for GDM development.
In addition, exposing rats to HST during pregnancy raises
the levels of OS which is associated with β-cell defects
hence increasing the chances for GDM.African Centre of Excellence for
Rodent Pest Management and Biosensor Technology
Development (ACEII-IRPM&BTD) projec
Mechanisms of gestational diabetes mellitus using rat model
No full textPhD ThesisGestational diabetes mellitus (GDM) is a form of
hyperglycemia due to carbohydrate intolerance that begins
during pregnancy. This may be due to insulin resistance or
impairment of insulin secretion during pregnancy.
Knowledge on the pathophysiology of GDM is important for
its management. Thus, the main objective of the current
study was to explore the mechanisms of GDM development
due to high fat diet (HFD) or heat stress (HST) in a rat model.
Specifically, the study was done to evaluate the role of
differential adipose tissue (AT) expansion, influence of
oxidative stress (OS) and to determine the role of placental
cytokine (tumour necrosis factor-alpha (TNF-α) and
interleukin-6 (IL-6)) in the development of GDM.
The study used Wistar rats as experimental animals. Rats of
8 - 10 weeks old were used and experiments were
conducted at the Small Animal Research Unit (SARU),
College of Veterinary Medicine and Biomedical Science
(CVMBS), Sokoine University of Agriculture (SUA),
Morogoro, Tanzania. Samples were analysed in research
laboratories in the Departments of Physiology, Biochemistry
and Pharmacology and Veterinary Anatomy and Pathology.
This thesis is divided into three chapters. Chapter one is on
introduction and literature review. It includes a general
introduction, animal models for GDM, factors governing the
development of GDM, establishing GDM models,
histopathology of pancreas during GDM, placenta and GDM,
objectives of the study, and organization of the thesis.
Chapter two comprises three manuscripts describing the
research findings. The first manuscript describes the
contribution of HFD to the development of GDM. The second
manuscript is on evaluation of how OS due to HST
predisposes rats to GDM. Findings on assessment of theiv
role of placental cytokines (TNF-α and IL-6) in the
development of GDM are presented and discussed in the
third manuscript. Lastly, general discussion, conclusion and
recommendations of the study are provided in chapter three.
Work described in the first manuscript evaluated contribution
of HFD in differential AT expansion and subsequent
development of GDM in Wistar rats. Pregnant and non-
pregnant rats were given streptozotocin (STZ) by a single
intraperitoneal injection or HFD throughout the experiment.
The animals were sacrificed by a combination of ketamine
50 mg/kg and xylazine 5 mg/kg on days 1, 8, 15, and 21 of
the experiment. Blood, AT (both visceral (VAT) and
subcutaneous (SAT)) and pancreas were collected and
analysed. In this study, STZ-treated animals had a
significant increase (p<0.05) in serum glucose and a
decrease in insulin, without changes in the size of
adipocytes. The levels of both serum glucose and insulin
were significantly high in HFD-fed animals (p<0.05); being
higher in pregnant (p<0.05) than non-pregnant rats. The
increase in glucose and insulin levels was associated with
an increase in the size (hypertrophy) than the number
(hyperplasia) of adipocytes. The increase in adipocytes was
higher in VAT and corresponded to insulin resistance and
GDM development than in SAT. Histologically, β-cells were
decreased in number and deformed in STZ groups while
maintained in HFD groups in both pregnant and non-
pregnant animals. This study concluded that intake of HFD
during pregnancy leads to AT expansion, which is one of the
risk factors for the hyperglycemia and development of GDM.
This study demonstrates in the second manuscript the
association between HST and GDM. Pregnant and non-
pregnant Wistar rats were maintained at 41 - 42°C for 21
days. On days 1, 8, 15 and 21 the animals were humanely
sacrificed by a combination of ketamine 50 mg/kg andv
xylazine 5 mg/kg. Blood samples were collected from the
heart for glucose, insulin, malondialdehyde (MDA) and
glutathione peroxidase (GPx) analyses. Pancreatic tissues
were fixed in neutral buffered formalin, and processed for
histopathology. The findings demonstrated that, in pregnant
rats, HST induced a significant increase in glucose in
conjunction with a drop in insulin levels than non-pregnant
rats (p<0.05). In addition, heat treatment was accompanied
by an increase in MDA and a drop in GPx levels. Histological
examinations of the pancreas revealed damaged β-cells
from day 15 and a reduction in the number of β-cells by day
21 of the experiment in pregnant rats. These results suggest
that HST raises the levels of OS in pregnant rats more than
in non-pregnant rats and increases the chances of GDM as
it is associated with β-cell defects in the pancreas.
Findings on serum concentration and placental production of
TNF-α and IL-6 of HFD-given rats during pregnancy and
their correlation with the development of GDM are presented
and discussed in the third manuscript. Pregnant and non-
pregnant rats were given STZ single IP injection or HFD
throughout the experiment. On days 1, 8, 15 and 21, the
animals were humanely sacrificed by a combination of
ketamine 50 mg/kg and xylazine 5 mg/kg. Blood samples
were collected from the heart for glucose, insulin, TNF-α and
IL-6 analyses. Placenta samples were dissected, fixed in
neutral
buffered
formalin,
and
processed
for
histopathological and immunohistochemical analyses for
TNF-α and IL-6. The levels of serum glucose and insulin
were significantly high in HFD-fed animals (p<0.05); being
higher in pregnant (p<0.05) than non-pregnant rats. The
increase in glucose and insulin levels was associated with
an increase in serum levels of TNF-α and IL-6; which were
higher in HFD pregnant than non-pregnant animals on day
21 of the experiment. Histologically, placenta tissues of STZ-
treated animals were severely congested with blood vesselsvi
on days 15 and 21 compared with those from HFD-fed rats
which had low congestion on day 21. In both pregnant and
non-pregnant rats, immunostaining intensity for TNF-α and
IL-6 was high in HFD and STZ-treated animals on day 15
and 21. The findings of this study show that intake of HFD
during pregnancy leads to an increase in the levels of IL-6
and TNF-α in the placenta towards the end of gestation
resulting in insulin resistance and hyperglycemia that may
predispose to GDM.
Therefore, Intake of HFD during pregnancy causes AT
expansion as well as increase in the levels of placental
cytokines (TNF-α and IL-6) resulting in insulin resistance and
hyperglycemia, which are risk factors for GDM development.
In addition, exposing rats to HST during pregnancy raises
the levels of OS which is associated with β-cell defects
hence increasing the chances for GDM.African Centre of Excellence for
Rodent Pest Management and Biosensor Technology
Development (ACEII-IRPM&BTD) projec
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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