4. Discussion
PE is a multisystem disorder that remains a major cause of maternal and fetal morbidity and mortality. Yet, no preventive measures are known to preclude the occurrence of the disease. Free radical damage and several metabolic derangement have been implicated in the pathophysiology of this condition (Rodrigo et al., 2005). This study aimed to evaluate the role of oxidative stress and markers of tissue damage as indicators risk and of pathogenesis of preeclampsia in pregnant Sudanese women.
In the present study the ages of the two study groups were not statistically different, while the body mass index was significantly higher in preeclamptic women than control group.
It has been established that hypertension during preeclampsia is associated with increased maternal vascular sensitivity to angiotensin II and agonistic autoantibodies to the angiotensin II type I receptor via activation of endothelin-1 and oxidative stress (Brewer et al., 2013). Several approaches to improve control of blood pressure were highlighted: inhibition of ANG II activity, by either blocking angiotensin II type 1 receptors or angiotensin-converting enzyme, or by preventing oxidative stress by administration of antioxidants (Palm and Nordquist, 2011). Without a proper intervention, microvascular endothelial cell injury plays a central role in the pathogenesis of preeclampsia. On that account, end organ damage is mostly directed towards organ systems highly dependent on the microvasculature for normal function including the kidney (Turner et al., 2015).
The excessive cellular activity associated with the process of placental ischemia leads to overproduction of uric acid which serves as a marker of the disease, with abnormal levels seen much earlier than the detection of proteinuria (Enaruna et al., 2014). This study revealed that the mean serum uric acid and creatinine concentrations were significantly higher in preeclamptic women compared to controls. Uric acid concentrations showed significantly positive association with the lipid parameters TC, LDL, TG, and the selected markers of complications LDH, AST, CK, and creatinine. Previous studies, indicated the association of uric acid level in preeclampsia, and its insinuative function as a marker of oxidative stress providing index for early diagnosis and clinical severity of the PE (Enaruna et al., 2014, Magna and Sitikantha, 2012). Other reports also showed that, serum uric acid and creatinine concentrations seem to be useful parameters to predict maternal complications and the management of women with PE (Razia et al., 2013, Suchanda et al., 2011, Sangeeta et al., 2013). In normal pregnancy, uric acid concentration initially falls 25-35% due to elevation in renal clearance secondary to increased glomerular filtration rate (GFR) or reduced proximal tubular re-absorption due to changes in its production rate. Later in pregnancy the serum uric acid level increases possibly due to raised fetal production, altered renal function and increased activity of xanthine oxidase (Corominas et al., 2014, Bainbridge and Roberts, 2008, Powers et al., 2006).
Ischemic placenta in preeclampstic women subsequently becomes hypoxic leading to its tissue breakdown which provides an additional source of purines for generation of uric acid by xanthine oxidase (Bargale et al., 2011, Anjum Sayyed, 2013).
Furthermore, uric acid can promote endothelial inflammation, damage and dysfunction, therefore PE, which is characterized by widespread endothelial dysfunction might be promulgated by uric acid (Martin and Brown, 2010). Uric acid decreases nitric oxide production by the endothelial cells due to its endothelial dysfunction action (Coutinho et al., 2007). In addition, it stimulates human monocytes to produce the pro-inflammatory cytokines IL-1? IL-6 and TNF-?, which are also elevated in the circulation of experimentally induced hyperuricemic animals as well as preeclamptic women. In preeclamptic women the increased concentration of circulating TNF-? was positively related with circulating uric acid concentrations (Bainbridge and Roberts, 2008). Acute rise in uric acid concentrations in animal models induces endothelial progenitor cell (EPC) mobilization. Uric acid was predicated to act as a signal for endothelial damage promoting repair of damaged vessels through EPC mobilization(Patschan et al., 2007).
The increased systemic oxidative stress can decrease nitric oxide bioavailability and cause pregnancy complications. It has been postulated that nitric oxide is important for facilitating the renal hemodynamic changes that occur during a normal pregnancy and blood pressure regulation (Hung et al., 2010).
Because during gestation there is a physiological increase in the glomerular filtration rate (GFR) and reduction of serum creatinine, even mild elevations of the latter can indicate renal function insufficiency. Severe PE can lead to deterioration of kidney function, chiefly in women with previous chronic kidney disease (CKD) and GFR below 40 mL/min/1.73m2 (2.5 mg/dl will experience preterm delivery, and >40% develop preeclampsia. Women who initiated pregnancy with a serum creatinine>2.0 mg/dl had a high (33%) likelihood of an accelerated decline in renal function during or immediately after pregnancy (Maynard and Thadhani, 2009). Hence, it is reasonable to consider the concentrations of uric acid and creatinine in women with PE.
PE can affect every maternal organ, predominantly the vascular, renal, hepatic, cerebral and coagulation systems. LDH levels were significantly elevated in women with PE and eclampsia and significantly correlated with high blood pressure as well as poor maternal and perinatal outcome. Extracellular activity of LDH increases under the condition of oxidative stress, since the cell integrity can be disrupted during the lipid peroxidation process (Jaiswar et al., 2011). Higher serum LDH levels were associated with increased incidence of maternal complications like placental abruption, renal failure, HELLP syndrome, cerebrovascular accidents; preeclamptic women with higher LDH concentrations >800 IU/l were more likely to have complications and neonatal death (Jaiswar et al., 2011). In this study 35 out of 111 patients (31.53%) had moderately to highly elevated LDH levels (600–800 IU/l).
Liver may undergo periportal hemorrhagic necrosis giving rise to elevated enzyme levels (Sibai, 2004). In contrast to normal pregnancy which is generally associated with normal AST, in PE AST concentrations was found to be elevated (Delic and Stefanovic, 2010). In accordance, the present study showed that the serum level of AST was significantly higher in preeclamptic women than control group. Similar findings were reported and revealed that the serum LDH and AST concentrations were significantly higher in preeclamptic patients compared to normal pregnant women and stated that LDH and AST may be increased due to liver damage (Rubina and Tabassum, 2008).
Creatine kinase (CK) is associated with high blood pressure, and it is also a better indicator of heart or muscle damage (Johnsen et al., 2014). CK is a main predictor of blood pressure, and this is thought to largely depend on high resistance artery contractility (Taherzadeh et al., 2015). LDH and CK were found to be elevated due to cellular damage in preeclamptic women, and have a significant association with various maternal complications specially cardiovascular and fetal outcomes (Purnima and Sonal, 2013, Jaiswar et al., 2011).
In this study, risk estimates considering complications parameters LDH, CK, uric acid and creatinine, preeclamptic women have had 2, 2.7, 5.8, and 1.6 times risk of developing tissue damage respectively. In the regression model, CK and LDH elucidated as important predictors for increase of the blood pressure.
PE is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of NO and tissue damage caused by increased levels of ROS (Matsubara et al., 2015). Vascular function modulated by the interference of ROS and NO. Increased ROS production seems to suppress the expression and function of endothelial NO synthase (Boger et al., 2010).
NO exhibits multiple and complex biological functions and many of its effects can be mostly attributed to its strong oxidant capacity. Thus, NO is an important mediator of immune homeostasis and host defense, and changes in its generation or action can contribute to pathologic states (Wander and Jean, 2010).
In this study, maternal serum NO levels were significantly low in the preeclamptic women compared to controls. NO was negatively and significantly correlated with SBP, DBP, TC, LDL, TG, LDH, AST, and CK, While, HDL and TAC showed positive and significant correlation. Several reports ascertain the decreased levels of NO in PE, and its negative correlation with body weight, systolic blood pressure and diastolic blood pressure (Ehsanipoor et al., 2013, Sharma et al., 2011, Saha et al., 2013, Tayal et al., 2014). In contrast, Norris et al. (1999) reported that the production of NO was significantly higher in the uteroplacental, feto-placental, and peripheral circulation in PE compared to normotensive pregnancies. They attributed the marked increase in NO levels to compensatory mechanism to the pathological effect of PE (Norris et al., 1999).
In normal pregnancy, NO derived from endothelial nitric oxide synthase (eNOS) contributes to the maintenance of vascular tone to increase uterine blood flow (Moncada and Higgs, 2006). An up-regulation of eNOS, resulting in increased NO production has been shown to contribute to increases in uteroplacental blood flow via changes in vascular tone (Sandrim et al., 2008). In addition, there is evidence that genetic eNOS polymorphisms may affect the susceptibility to hypertensive disorders of pregnancy (Sandrim et al., 2010). A study on 3 polymorphisms of the eNOS gene and the plasma nitric oxide concentrations was conducted in a population of Chinese origin from mainland China. Two variants 298Asp allele and eNOS 4a were strongly associated with higher plasma NO concentrations in pregnant women and suggested to modulate PE susceptibility (Chen et al., 2014).Vascular tone is altered by the interference of ROS and NO, increased ROS production seems to suppress the expression of eNOS and hence reduced production of NO (Farrow et al., 2008). In fact, several studies have shown that impaired vascular relaxation in PE has been attributed to reduced bioavailability of NO produced via endothelial NOS (Eleuterio et al., 2013). A reduction in the bioavailability of NO and the imbalance between ROS and antioxidant activity seem to play a critical role in endothelial dysfunction contributing to raised in blood pressure and hence pathogenesis of PE (Sankaralingam et al., 2010, Alpoim et al., 2013). NO is also a potent inhibitor of platelet aggregation and activation by both cGMP-dependent and -independent mechanisms (Crane et al., 2005). Drugs that target various components of the nitric oxide soluble guanylylcyclase pathway can help to increase NO bioavailability, and the delivery of exogenous NO is an attractive therapeutic option (Johal et al., 2014).
Total antioxidant capacity (TAC) parameter summarizes the overall activity of antioxidants and antioxidant enzymes (Prior et al., 2005). Evaluating oxidative stress by measuring TAC can lead to a better understanding of free radical damage in oxidative stress related diseases like PE which would be useful to identify the patients with increased risk of progression of the disease and also for monitoring and optimization of antioxidant therapy (Suresh and Annam, 2013). In our study, the serum level of TAC was statistically low in the preeclamptic patients compared to controls. TAC was negatively correlated with SBP, DBP, BMI, TC, LDL and LDH, while it was positively correlated with HDL and NO. Risk estimate considering antioxidants revealed that pregnant women that have low level of NO and TAC had 7.6 and 2.6 times higher risk to develop oxidative stress which in turn leads to development of PE. Study findings are in agreement with the study of Hasan and Dina (2014) who reported that the serum level of TAC was significantly low in preeclamptic cases signifying that the decrease in TAC leads to an imbalance between prooxidants and antioxidants in those women that go on to develop PE(Hasan and Dina, 2014). Oxidative stress reflects an imbalance between the formation of oxidative substances and the innate antioxidants that make up the endogenous defense system (Buonocore et al., 2010). During normal pregnancy there is a slight increase in oxidative stress, even in the presence of antioxidant systems (Raijmakers et al., 2001). In PE, the Abnormal vascular development of the blood vessels in the placenta leads to reduced placental perfusion and induce hypoxia which is by itself a potent stimulus for ROS formation (Rodrigo et al., 2005).
A genome-wide transcriptomic view identified genes involved in lipid metabolism, angiogenesis, hormone activity, and inflammation to be significantly altered in placenta from obese women. These studies provide evidence for increased lipids and decreased TAC in placenta from obese women, and pinpointed key signaling pathways (increased JNK/FoxO4 signaling) and downstream mediators (HIF-1? and VEGF-A) that provide a link between maternal-obesity, placental inflammation/oxidative stress, and altered angiogenic factors. Obesity provokes cellular stress, which may in turn adversely affect placental development and function(Saben et al., 2014). Antioxidants may be utilized to greater extent to counteract and scavenging free radicals, resulting in the reduction of their levels (Manisha et al., 2015).
The limitations of this study include the relatively small sample size. There were no follow up criteria set. Even with this limitation, the findings of this study serve as ground for further studies to better understanding the associations of total antioxidant capacity and nitric oxide levels with preeclampsia.


4. Time Management: Changes are inevitable during the project, there are few projects that are completed on the time according t the original project plan. There are number of changes that can be occurred during the project:
a) Type of change
Duration of the whole project can be increased, due to number of reasons such as delayed in the external deliveries such as hardware tools and other resources that are important for the execution of the process.

Experience of the team members significantly contribute in the delay of the project. Team members have a different experience, so some can do tasks on time and might be others not, consequently, during the project, activities will not be complete on the time.

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Weather changes also leads to different type of changes in the project, such as
Other changes such as technical change, financial change, some are political or people related.

Sometime clients are getting changed their requirements, on which they were agreed on the initiating state, that affects the execution time of the project.
Financial issues also put a impact on the duration of the project
b) Time of occurrence
Time management can be changed at ant time of the project because time depends uoan the every activity of the project
So, any activity can delay at any process such as at the beginning of the project: delay in the selection of the project team, consequently, it impacts on the whole time management
It can be happen in the executing time. For example, delayed in the paymets or materials, which can cause the change of time mangement of the whole project
c) Corrective actions
Manager should create a realistic project schedule that offers a proper guideline to monitor the project from start date to end date.

Important tools should include by the Manager such as Gantt chart, Critical Path Analysis
Critical Chain Scheduling(CCS) also help to manage the time dimensions for the project. In CCS, recourse can work on multitasks at one time.

Project buffer is also good choice for controlling the time management in the project.

They should prepare assignment reports which includes that who does what and when with the dates.

Must be determines the dependencies to start the next activity.

Project manager should utilize the project management software to boost the time management. Nowadays a lot of project software are available for the projects.
Proper Network Diagram about the sequencing of the activities.

Once activities are identifying, then allocate the people, material, resources or equipment that required to complete those activities.

d) Affected deliverables
If the time management changes, the deliverables cannot deliver on proper time
And it impacts the reputation of the company.

Dissatisfaction between the stakeholders.

Company can loose the further contracts with the same stakeholders.

Government can impose ban on that prduct after log time
5.Cost Management: Cost management is the most paramount aspect of the project management. During the process of cost management, managers use different type of tools and techniques to ensure that project should be completed in the estimated budget
Change of type:
As a number of changes occurred in the life cycle of the project have a grat impact on the cost of the project. For example, if firstly manger is spending on the simple design in the initial stage and in the executing phase, clients demand for the decorative design, this will affect the cost management.

Shortage of the lobar: If during the project, there will be a shortage of the labour in the market, then company will have to hire the labour from outside with the high pay rate.
Cost management is also affected by the type of material. During the time of planning, if they include the low quality of material and during the time of testing, stakeholders demands for the high quality.
As we know technology is changing day by day. Technical updates can change the cost of the project, especially in the long projects, manager can put tech solutions with upgoing version and can be out of date by planned end. So, at that stage, new software has to put into the project, which can be more expensive than oldest one.

Exchange rates: if the material such as equipment and other software is imported from other states or countries and the exchange rate do not remain same like as beginning of the project, then it will increase the cost of the project.

The lack of financial for the completion of the project has a significantly impact on the project. If the expenses of the project increase significantly as compared to estimated cost of the project at the beginning or delayed in the payments can effects the cost management.
b) Time of occurrence
Cost changes can occur at any phase of the project, when any change held in the project, it affects the cost management.

c) Corrective actions
As a project manager, cost management plan should properly generate, contains full detail of the cost estimate, cost budgeting, cost controlling.

Manger should account all the software, hardware, labour, material cost while preparing for the cost budget plan and it is done by arranging meetings with the team members and stakeholders.

Updating yourself can help to control the cost. Manger can generate strategies that how he/she can use funds efficiently in the future.

Procedures, policies and documentations for the planning, managing, expending and controlling the project cost would be a fruitful for the progress of the project.

Manger should take in to the account about the updating project costs and cost baseline.
Regularly checking of the cost that is accounted to the project at the end of the month and it can be associate with the approved budget.
Projects should be tracked by project managers regularly, appropriately handle the changes occurred in the scope management, which might be the causes of the cost estimation change.

Risk contingencies should be prepared by the manager and let to know to the whole project team as well.
There are three main tools: earned value management(EVM), To- complete performance index(TCPI) and forecasting, which can help to measure the cost of the project.

d) Affected deliverables
6. Quality Management: Quality of the project means the project has satisfactory requirements. In the project management, quality means reliability, performance, functionality and suitability of the project that fulfil the client’s needs. To control the quality, managers should follow the phases of the good quality management plan.

a) Change of type:
If the project manager and project team is not skilled, they do not know how to manage the quality of the project, it impacts the project quality.

Quality of the project is also associated with the quality of material and equipment as well. For example, if the manager is using the good quality of software then the project’s quality will be good. That software can handle a number of tasks at one time, it will not buffer.

A poor quality management time.

Time of occurrence
Quality of the project can occurred
in the last stage of the project, because the testing task is takes place in the end of the
Corrective actions
Good quality of material should be used in the projects, so that there is no complain about the quality of the project
For the process of the auditing the quality experienced people should be hire.

Manger should use the technique of design of experiments which contains the information about the different type of variations who has a great impact on the quality.

In quality assurance, there is two processes, benchmarking in which the progressive project can be compare with other similar projects and quality audit, which gives ideas about the improvement of the quality.

Case and effect diagrams can help to find the root cause of the bad quality and in this process , that product can be sent back to the production department.

Control chart and run chart try to protect the project from the defects and show the up and downs during the project respectively.

The control function must be follow by the manger properly, from the engineering department to construction, from lower level to higher level, everyone has a same goal of quality and cost effectiveness.
Inspection about the quality of the project should be calculated regularly and deliverables inspected thoroughly.

The stakeholder’s expectations should be documented, so that after some time team cannot forget the main requirements of the project.

Affected deliverables
Without proper quality management plan, a project can contain the chances of high risks.

Without proper details of needs of the stakeholders, projects can be derailed if there is number of interpretations about how project can determine.

Pure quality causes the wastage of the time. After completing the project, if the project has a low quality, the whole team rework on the same project. Consequently, delayed deliveries, and companies cannot afford for the delayed deliveries as they already sighed on the contract, company can get a penalty for delaying services.

If the stakeholders not satisfied with the standards of the quality, project can be reopen, which again requires the cost to work on it.
Once you delivered the project and some quality issues come up with that project, then relation of customer and organisation can become worst, which is very dis advantageous for the o rganisation in the market,
7. HR Management: The precious part of the project is its people. Any organisation can rank as first in the competition, if the company has a talented and skilled employee . Human Resources Management organize and manage the whole project team from high level to low level, who is involved in the project, externally or internally from the creation of the project to its success.
a) Type of change:
Selecting the project team(PT) is the key responsibility of the human resource management, if HR select the wrong skilled people for the project team it can affect the project extremely bad.

More than just hiring the people in the project team, it the key responsibility of the HR to select the people who have great competencies, multitasking ability and intest in the project.

PT requires their freedom of working during the cycle of the project, so HR should hire the mature project manager, who can make balance progressively in the freedom of the team
Another reason of occurring the change is HR should consider where they are hiring project team, mostly with the internal employees, but if there is the requirement they can do externally as well.

b) Time of occurrence
Changes can be occurred in the HR management in the initiating phase of the process
It is the first stage of the project, when company selects its HR, if they feel their HR is not perfect they can change it.

Organisation has a authority to change HR at any phase of the project, when they feel, HR not properly guide the project team and it is unable to create a good relations between teammates and with stakeholder.

c) Corrective actions
Human resource management should make effective selection plan to hire a perfect people in the project team.

4 processes include in this, human resources planning, acquiring the team, developing and managing the team properly.

HR responsible for the track of the team, and provide them motivation and make the employee positive towards work and if prepare the feedback for every person who is attached to the project.

Intrinsic motivation is about the people’s own interest in the project and extrinsic motivation to avoid the penalty and hike the recognition.

Organisational issues should be resolve by HR properly by adding all the strategies which are helpful to make environment of the organisation operative.

Responsibility assignment matrix paly a paramount role in the managing the project and project team which contains the responsibilities and the entire work in the form of WBS.

Staffing management plan and resource histogram contains the information about when people should add in the project and when take-off and number of resources that require for whole the project.

HR should prepare recourse levelling for the project, in this number of recourse are allocated to different tasks, this technique useful when shortage of the resource.

Tools to handle the PT are observation and conversation, interpersonal skills, conflict management and project performance appraisal.
HR should try to develop some good relations between the teammates for the successful project, for that they can adopt a Meyers-Briggs Type Indicator(MBTI) tool, to judge the personality preferences.

d) Affected deliverables
Human resource management is responsible for the project team, if HRM not works properly, it impacts on the quality of the team, and might be the team would not be much skilled and experienced, which has the direct impact on the performance
The main purpose of the training to provide the information about the business’s culture and about its history to the novice, so unsuitable information can stray the people from the project’s track.

8) Stakeholder and communications management: Stakeholder management means the maintain the expectations of the stakeholder regarding the project and product. This approach is designed for the engagement of the stakeholders, project does not mean that provide with good scope, on time and with approved budget, it should be fulfilled the requirements of the clients and stakeholder, for that the participation of the stakeholders is extremely pivotal.
a) Type of change
If company will not communicate time to time with the stakeholders, may be the mind of the stakeholder change during the time;
Requirements could be changed
Status of the position of the stakeholder can be changed, for example stakeholder can change from internal to external.

b) Time of occurrence
These changes can be happened any time if the life cycle of the project
Mostly communication changes occurred in the executing process, because it is third process of the project
This id the stage when communications have a high priority, managers need to communicate with stakeholders for diffident purposes.
c) Corrective actions
Manger should follow the stakeholder management plans and all the process that includes in this.

Mangers need someone who can speak on the outputs, who can give ideas on the delivery so that they can do changes if it requires
Identification of the stakeholders means who is impacted by and who impacts the project is the key ingredients of this management. Then make the strategies to engage them into the project and continuously manage it.
With the help of stakeholder register, it become easy to know that stakeholder is internal or external and what are their requirements and what is their relations with the organisation.

For the communications with the stakeholders can be proof as the fruitful for the success of the project.

In the communication management, information should be collect, write, mange, distribute and store properly to inform the stakeholders.

Organisation can use different techniques and tools for the communication such as face to face meetings, formal meeting, chairing a meeting.

Different type of communication can be used to manage the communication with the stakeholders such as interactive communication: two or more people meet to exchange the information, push communication: information send to the other people through any technology and recipients receives the information and pull communication: when anyone demands the in formation, than company send that information to the person.

Performance reporting should be given to the stakeholders, how the resources are being used to progress the project.

Organisation should have a proper communication infrastructure to make sure communication management.
d) Affected deliverables
If the stakeholder management is not proper in the project it impacts negatively on the performance.

If the communication and stakeholder management is not properly carry out it creates a number of misunderstandings between the stakeholders and the organisation.

Misunderstanding could be a related to the cost of resources, number of people, requirements of the clients
Failure in good communications can causes the dissatisfaction between the project team, manger and stakeholders and the customers as well.


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