Measuring Skin Blood Flow and Vascular Permeability

Measuring Skin Blood Flow and Vascular Permeability The aim of this experiment is to compare the dose-related inflammatory response demonstrated by the skin following injection of histamine and bradykinin two inflammatory mediators. Methods used will demonstrate a non-invasive, quantitative way to measure blood flow and vascular permeability in the skin. INTRODUCTION The acute inflammatory reaction occurs to protect the body in response to a pathogen or other noxious substance. There are two components: adaptive immunological response (which is described as a more specific immune response) and the innate response which occurs immediately upon infection and consists of both vascular and cellular effects (Rang and Dale, 2007). The innate response will be studied in this experiment, specifically in the skin. Bradykinin and histamine are inflammatory mediators involved in the innate response and will be studied at different doses. The results can be used to provide a potential target for therapeutic use: further experimentation would allow the addition of inflammatory mediator antagonists to potentially reduce the four cardinal signs of inflammation: pain, heat, redness and swelling. The local oedema and vasodilation give rise to the wheal and flare. The reddening represents vasodilation of small arterioles, and the increased permeability of the post capillary venules is represented by the wheal. The flare occurs due to stimulation of sensory nerves causing release of vasodilators. This is known as the triple response. It will be the wheal and flare that will be measured and used to describe the action of the two inflammatory mediators. METHODS The methods used were in-vivo; the doses of inflammatory mediators (and saline control) were injected into 10 volunteers. It was confirmed there were no known allergies to either bradykinin or histamine and all correct health and safety procedures were followed. Each of the 10 subjects were injected first with 25ÃŽ ¼L of saline solution, used as a control to show there was nothing in the saline (that the inflammatory mediators were diluted with) causing an inflammatory response. This was followed by doses of 10, 30, and 100ÃŽ ¼M histamine for 5 subjects and the same doses of bradykinin for the other 5 was added, all at 30 second intervals. These were administered using a sterilised syringe which contained the correct concentration. The doses were injected into forearm intradermally and care was taken to ensure the complete volume of 25ÃŽ ¼L was taken up by the skin. Each successive administration was slightly further up the arm giving space for each of the four doses and to try and prevent the flares from overlapping. At periods of 2, 5, 10 and 15mins a clear sheet of acetate was placed over the centre of injection and the wheal and flare were circled using a non-wipe pen and repeated for each respective dose. This provided the area of the wheal and flare at each of the given concentrations at each of the given periods of time following injection, for each respective inflammatory mediator. The flare was cut from the acetate and weighed accurately to 4 decimal places. Subsequently, the wheal was cut from the centre of the flare and was also weighed. This process was repeated for each of the doses of inflammatory mediator (bradykinin and histamine) and for the saline control also. A 2cm2 square was ruled onto the acetate which was also cut out and weighed. This provided a conversion between weight and area, allowing the area of the wheal and flares to be calculated (credit to Dr. Dean Willis).This data was tabulated and can be found in the appendix and illustrated in the results. The data was checked for any anomalous values that could be defined as incorrect based upon logical criteria. Group 1 for the histamine set had flare sizes of 0cm2 however, had wheal sizes greater than this. Therefore this data was removed to all analysis as it is clearly incorrect. The data was then averaged for each of the 5 subjects for both histamine and bradykinin. There were two independent variables: time and concentration; and two dependant variables: wheal and flare areas. The independent variables were illustrated on separate graphs and the wheal and flare sizes were imposed on the same. To produce graphs to illustrate the change in area with concentration, first the largest average value recorded for each concentration was selected and tabulated. This allows comparison not only between different concentrations of the same mediator, but also between bradykinin and histamine. This also means time was irrelevant because it did not matter at which time recording the values were selected The increase in wheal or flare size due to inflammatory mediator was calculated (i.e. the difference between the wheal or flare recorded and saline). This increase in wheal or flare was plotted against the respective concentration and the concentration was plotted in log scale to illustrate a dose-response curve. To illustrate the change in area with respect to time, firstly, the data was scanned to select a concentration at which the change in wheal and flare was best illustrated. This concentration was taken to be 100ÃŽ ¼M (for both mediators to ensure continuity and to allow comparison). The Average wheal and flare size was then plotted against time for both bradykinin and histamine. RESULTS Removed data: (see appendix) Group 1 of the histamine section has a flare size of 0.000 recorded with a wheel size of greater than this. This is likely to be a systematic error in not realising the flare is indeed underneath the wheel and not visible, in this case the flare is the same area of the wheel. However this is just speculation, and in order to ensure all data used is correct saline recordings for each time interval both wheel and flare areas for group 1(histamine) were removed from analysis. The wheal size only increased slowly with increased concentration of bradykinin to a maximum of 0.414 at 100ÃŽ ¼M. The value at 10ÃŽ ¼M was actually lower than that for saline. This is not a significant decrease however as it was taken as a decrease of 0.04cm2, which is a small area and the limitations of the experiment are likely to be the cause. The flare size, however, increased more with increasing concentration. The size of the flare is likely to represent a dose-response curve with a classic sigmoid shape if the concentration of bradykinin were to be increased further. However, due to the nature of the experiment this would not be practical as a much large concentration of inflammatory mediator could be dangerous for the subject. It is also shown that the maximum flare area at 100ÃŽ ¼M was recorded at 10mins. It can therefore be deduced that it was relatively slow acting; however it cannot be determined whether the maximum value was indeed at 10mins recorded as 7.808cm2. Equally the flare area could have rose to a maximum between 5-10mins and decreased, or rose to a maximum after 10mins and reduced to that recorded at 15mins. It can be shown that at the lowest concentration (10ÃŽ ¼M) of histamine that there is only a small difference of 1.194cm2 between the maximum flare-area recorded by bradykinin. It can therefore be deduced that histamine caused a larger flare than bradykinin at the same concentrations. Ahe general trend is similar to that of bradykinin: small increase in wheal area, large increase in flare area. The maximum wheal area was only 0.03m2 larger than that recorded by bradykinin. Again, the wheal area had very little variation with time: increase of 0.2cm2. The flare area was at a maximum recording of 18.625cm2 after just 2mins. Therefore, it is likely to have been at the maximum area before 2mins. This shows that histamine is faster acting than the bradykinin. There is a relatively linear decrease with time to a minimum value of 9.120cm2 recorded at 15mins. The flare area did of course continue to decrease after the 15minute period until there was no apparent inflammation, likewise for bradykinin. DISCUSSION As mentioned previously, the innate inflammatory response consists of both vascular and cellular effects. Vascular events begin by dilation of post capillary venules, causing an increased blood flow. Vasodilation is caused by the action of histamine (and other inflammatory mediators), leading to increased local blood flow and an increased vascular permeability causing a local oedema. The fluid contains the components a proteolytic enzyme cascades producing bradykinin. Bradykinin is also an inflammatory mediator causing further vasodilation and vascular permeability leading to local redness and oedema respectively. This gives rise to the cardinal signs of inflammation: redness, swelling, heat and pain (also loss of function). The sensation of heat and pain ascend through sensory neurones via the spinothalamic tract. Upon the presence of a pathogen, pathogen associated molecular patterns (PAMPs) are recognised on the surface of bacteria and causing the release of cytokines from macrophages. Cytokines are small polypeptides involved in cell-signalling and orchestrate inflammation. This allows expression of adhesion molecules in the endothelial cells. Phagocytes then adhere to the endothelium and migrate towards the bacteria where phagocytosis takes place. In addition, exudation of fluid occurs in response to an increased vascular permeability due to a combination of cytokine and inflammatory mediator action (as well as increased vasodilation in response to inflammatory mediators). The fluid allows four enzyme cascades to occur producing inflammatory further inflammatory mediators by proteolytic cleavage from their native (inactive) state. One of these cascades gives rise to bradykinin (Pocock and Richards, 2006). Histamine is released in response to products of other enzyme cascade pathways such as C3a and c5a which make up part of the complement system. C3a and C5a bind with receptors on the surface of mast cells, causing a rise in intracellular calcium leading to exocytosis of histamine. Simple injection of bradykinin or histamine mimics these pathways. Bradykinin is a vasodilator and also increases vascular permeability leading to a local swelling. This is consistent with the findings in this experiment. After Intradermal injection of bradykinin, the typical triple-response was apparent; there was a wheel and flare as described by Sir Thomas Lewis. Breakdown is by kininases and it is likely to have cleaved bradykinin at a relatively fast rate due to the short lasting effect at 100ÃŽ ¼M where the flare area began to decrease after just 10mins. Histamine has a similar action to bradykinin but found to act faster and also found to be more potent at each concentration tested. The flare area was at a maximum after just 2 minutes. Histamine acts on H1 receptors to dilate blood vessels, therefore it is likely there is a high expression of H1 receptors at the skin surface, or histamine has a great affinity for its receptor. It is likely to be a combination of both, however to confirm these ideas, experiments could be conducted on other tissue perhaps on organ tissue in-vitro using an animal model. This response is characteristic of the acute inflammatory pathway; however, more recent studies suggest that histamine has a role in chronic inflammation involved in the immune response (Jutel et al., 2009). There is regulation of T-cells (which make up part of the immune response) by H1 and H2 receptors. There is a 4th histamine receptor, H4 and further evidence for the role of histamine in chronic pathways comes from expression of H4 receptors on immune cells (Jutel et al., 2009). It is apparent from figures 1 and 3 that an increase in either inflammatory mediator resulted in an increase in wheel area. As previously described, this is due to release of vasodilators from sensory nerves in response to stimulation. So it can be deduced that a larger concentration of bradykinin or histamine indicates a larger infection and therefore the cascade process is accentuated. The wheal area stays relatively constant in both cases, this could be due to no addition action of inflammatory mediators on the vascular permeability, or indeed there is already a full effect i.e. the post capillary venules are a permeable as possible. However another hypothesis could be that additional permeability would only lead to a further decreased extracellular solute concentration which would simply be reabsorbed by osmosis. STRENGTHS AND LIMITATIONS Strengths of the experiment were in that humans were used and methods were in-vivo. Therefore there is no reliance on animal models to use as a comparison. All subjects were of a similar age and gender was at random, hence, generally similar responses were found between each group. Limitations were found to be in injecting the inflammatory mediator intradermally. There was a tendency for not all of the solution to actually enter the skin, thus decreasing the number of moles of inflammatory mediator. This however did not seem to effect the results too greatly as 5 repeat groups would allow for some small error. It is still clear from the experiment that the aims were met and the mediators compared. Furthermore, measurement of the area was not particularly accurate. Firstly it was hard to judge the size of the wheel and flare and there was a tendency for the flares to overlap and was often left down to judgment of where to define the boundary. There were a few further cases where the w heel size exceed that of the flare (in addition the case described in the results) however these were only small differences and could easily have been to variations in the measurement of the weight. If the wheal and flare were the same size, the acetate could have been weighed twice and hence the small difference. This would not have affected the outcome of the experiment however so the data was accepted. Better methods of measurement of wheel and flare area would be to use an imaging technique and record the change in areas digitally. This would allow for calculation of the change in rate of area with respect to time (via differential equations) which would give a good indication as to the potency and allow for a more in-depth comparison.

Anthropology social relationships Essay

Social relationships in most cultures and societies impact heavily on how a person perceives their world. People create their social world but are also shaped by it, and part of this social world is the social relationships that are formed between individuals. These relationships vary in kind from family and kinship to friendship. Kinship and family are types of relationships that have been widely studied in the attempt to study and understand a culture or society. And whilst these are important, relationships of friendship also play a large part in the way the individual’s personality is shaped and how they view their social world. Relationships of kinship or family ties are generally unavoidable and are formed through generations of families or cultural ties. Tribes and small villages are a good example of this where the members of these social circles are in frequent contact with each other and are somewhat limited to the generations within the physical boundaries of their social world. The formation of these relationships does not require much effort and they are expected to continue even if transformed over time. Positive relationships can become negative and vice versa. Look more:  social process theories essay Within the classification of family ties and kinship, the individual’s ties’ with ones family would be described with him/her in the centre, his parents above, children and their descendants below and siblings to either side (Morgan, 1870, p.10). Kinship ties include those where an individual does not have close genealogical ties with another rather is related through an unexpressed social tie, marriage or other wider social circles. If you take rural villages as an example, the degrees of these relationships can be measured in a somewhat circular pattern, where immediate family is in the centre, followed by those related by marriage, and then the members of the village in various degrees of closeness. The ties of family are expected to continue even after death, i.e. the individual is still a son to his parents but is also a father to his children, a brother to his siblings, etc. If the ties of kinship are those of a wider social circle than that of family; then ties of friendship are to be considered in the somewhat grey area in the middle. Relationships of friendship are more informal yet private to some degree and are usually based on some common interest or sharing (Beer, 2001). This sharing is not limited to material objects, but also to thoughts and secrets; thus friendship is a relationship that is heavily dependant on mutual trust and loyalty as compared to blood ties of family or kinship. Aside from those with family, most other relationships can be created, sustained in some way or ended by the individual, and each relationship will have its effect on perception or the shaping of the individual and his/her world. It is as such a given that these relationships can be created or impacted on by the actions of the individual or both parties involved. In order for a social relationship to be established outside of the setting of ‘family’ many events and actions take place. Social relationships are important to the individual as well as their social world, these relationships are often the foundations of the individual personality. From a young age the first relationship would be with members of the immediate family, however as time passes, the social circle or boundaries per se, of the individual enlarge to include others. These relationships are created from different situations, a child’s first school friends, the relationships between parent and teacher, relationships of friendship between those who share mutual interest and those of work to name a few. These relationships can be established in several ways; the exchange of gifts, the sharing of interests, cultural beliefs and identity, or a shared interest. Gift giving being the easiest to understand can be condensed into the action of give and take between two or more parties. This process is not always a positive attempt towards the continuation, formation or beginning of a relationship as the refusal to reciprocate the gift giving can be also seen as an indication to end the relationship. Social relationships require a certain measure of give and take, gift exchange, secrets, conversation, and opinion. Gift exchange plays a large role in social relationships as it can be used in several ways; an indicator for the willingness to engage in a relationship, the intention to continue a relationship, etc. However, gift exchange has two parts, giving and receiving, and these actions have different results depending on the situation. Drawing on the article by Theodore Caplow (1982) on the connection between gift giving and relationships one can begin to understand the impact these actions have on relationships. Caplow describes the gift exchange as being mostly among kin, however he also mentions that gifts were also given among co-workers, friends and couples. Caplow described the gifts given and received between primary kin as being in a pattern where the gifts given from an older generation within family were likely to go downwards, i.e. more gifts were given by those older than 18 to those younger than 18. This process of gift giving and reciprocity is slightly uneven and occurs mainly among kin members. Parents do not expect much in the way of gifts from children and children only gift with what limited capability they have. However the gift giving changes in other relationships, for example, between couples who are dating or among friends. As such, the relationship between kin cannot be truly described as a relationship that is insomuch created as much as it is inherent simply to the birth of an individual, so when considering the process of creating social relationships, one must consider the relationships formed outside the circle of immediate family. Gift giving between individuals as mentioned above, is seen as a way to continue a relationship; one person gives a gift and expects one in return. To reciprocate and gift in return would indicate that one intends on continuing the relationship. Yet despite describing the action of gifting and reciprocity in the term of material gifts, it is not always material gifts that are exchanged. Gifts can be given to those one intends on keeping favour with the expectation of asking for something at a later date, which is not necessarily another material object, but it can be something like favour within a political setting. Positive social relationships also require ongoing maintenance and can be ended at any given moment by the actions of one or both parties involved for example in the case of two neighbouring Brazilian families in the town of Monte Verde where an old friendship ended in a feud (Descharmes et al. 2011, p349). In this case there remained a relationship, however it was a transformed, hostile relationship of revenge where one family would murder a member of the others and the opposing family would reciprocate with the same. This reciprocal opposition transformed the relationship from a positive relationship to one of revenge. In this case we see how a relationship is transformed, but transformations of social relationships can also be positive in weddings for example where two members of separate families are united and a new relationship is formed where those two individuals are now members of the others family. Marriage is a very common form of transformation for a relationship and is found in almost all societies and results in reciprocal rights between both parties whilst also creating a social process where new relationship are set up between the kin of both the husband and the wife (Brix, JH 2010, pp162). These transformations of social relationship occur often but with various results. In the formation of relationships of friendship, two individuals may move from being ‘acquaintances’ to ‘friends’. Beer makes the distinction between friendship and kinship; where kinship is usually used to describe close personal ties, not necessarily genealogical, and friendship is a relationship based on sharing of time, problems, plans, hopes and thought. As such with the sharing of secrets and personal thoughts, friendship is a social relationship that requires absolute loyalty and trust, as if the relationship is broken off; these secrets can be revealed to others. Over time, these factors affect a person and the way they shape their social world. If we consider that the individual shapes his/her social world and that this world in turn shapes them, we may also consider the effect social relationships have on this social world per se. Relationships between family or kin will shape a child in the early stages based on the culture and beliefs passed down from the parents or adults in the child’s kin circle. However as time passes, the social circle expands to include school peers and other adults. The biggest effect is usually from the friendships that are formed with others from a completely different kin circle to the individuals own. To go into a deeper understanding of the individual’s social world we must also understand their relationships. Drawing on the article by Ortner, 1993, on a high school graduate class, as a case study, we are given examples of some relationships that are formed and maintained. Ortner describes her high school graduate class and their sense of â€Å"community† during and after their school years. She goes on to describe the structure of â€Å"class† within the high school. this idea of a â€Å"class† system depicts the social circle or world that the members of these â€Å"classes† were a part of. These social circles are described as including members who had similar backgrounds or interests. Furthermore she goes on to describe the relationships that were maintained after high school. These relationships tended to run in the same circles as they had been during school years. So by analysing the social relationships of the individual we are given a deeper understanding of the way they shape their world. The social structure we give our world often is dependant on how we structure our relationships with others. The social relationships that alter the perception of social structure for one person may not always be applied with the same results for all people. This is due the many relationships we build and maintain with others over time. The formation of social relationships are created, sustained, transformed and ended with the actions of the individual and sometimes without. We may find ourselves in a relationship with others that has simply arisen through the relationship with kin or family. Yet these relationships help shape us and the way we crate our social world. These relationships are constantly in flux and changeable with the time that passes as a relationship can also change with the passing of time without many major or drastic changes. As such, these relationships play a major role in how we perceive our social world and inevitably our sense of self. Bell, S, Coleman, S 1999, The Anthropology of Friendship, Berg, USA Beer, B 2001, Friendship, Anthropology of, International Encyclopedia of the Social & Behavioral Sciences, Elsevier Science Ltd, USA Caplow, T. 1982 Christmas Gifts and Kin Networks. Sociological Review 47 (3): 383-392. Descharmes, B, Heuser, EA, Krà ¼ger, C, Loy, T 2011, Varieties of Friendship; Interdisciplinary Perspectives on Social Relationships, V&R Unipress, Germany Morgan, LH 1870, Systems of Consanguinity and Affinity of the Human Family, University of Nebraska Press, USA Ortner, Sherry 1997 Fieldwork in the Postcommunity. Anthropology and Humanism 22(1): 61-80. Turner, V. 1964 Betwixt and Between: The Liminal Period in Rites of Passage. in J. Helm (ed.) New Approaches to the Study of Religion Seattle: American Ethnological Society pp. 4-20. Vaughn, L 2010, ‘Marriage and the family’, in HJ Birx (ed.), 21st century anthropology: A reference handbook, SAGE Publications, Inc., Thousand Oaks, CA

Bullying Is A Big Problem - 982 Words

Bullying Lynette Mather stated that, â€Å"What if the kid you bullied at school grew up, and turned out to be the only surgeon who could save your life?† This quote really spoke to me because it holds a lot of truth in it being that bullying or being bullied sticks with you forever whether or not you apologized for what you did back in your school days or not, those words and actions scar people forever and it is something that will remain with them for the rest of their lives. We are often blind to the fact that bullying is continuously a big problem in our society. This topic is important because almost everyone that we know, including ourselves have been affected by bullying in one way or another and we may not think what we do or have done is doing harm, but to other people we are hurting them in various ways and it can be very dangerous and lead to horrible things down the road. 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Timmers Definition of Law - 1201 Words

Timmer’s Definition of Crime â€Å"A definition of crime represents the legal conditions under which the state, as an instrument of an economically dominant class, exercises its power to punish.† I feel that the state maintains the capitalist order through laws. Primarily, control is done through the governing of consciousness of the population. The ruling class gives rise to their own ideology to protect themselves. Capitalism’s most subtle means of control is to try and manipulate the minds of the people. They try to dictate the future through the people’s thinking and overall living. This type of dictatorship is cultural, psychological, economic and political. When an existing order becomes threatened, the focus on crime rises.†¦show more content†¦E., Bridges, G. S., Weis, J. G. 2008). Punishment is based on deterrence and is aimed at providing the greatest happiness for all of society without harming oneself or others. During the Gr eat Depression rapid social change led to social disorganization that led to personal disorganization, which in turn lead to deviant and criminal behavior (Crutchfield, R. D. 2008). Social control was broken because of class differences, economic problems, cultural and ethnic issues. Crime rates can be reduced by states from necessary laws and solutions to social problems. Due to crimes many people have been killed, some have been harmed by other people. The states and the laws they are governed by are there to protect individuals from harm by other individuals. To the extent that states go to try and combat crime can, at times, be seen as going a bit too far in possessing the power that needs to be shown and enacted on when a person does commit a crime (Ãâ€"rmeci, Ozan 2011). There has to be order in our society, but to what extent, is a person’s dignity and integrity put at risk or harmed. â€Å"Under capitalist social relations, direct political force is not neces sary for the maintenance of economic exploitation: it is sufficient for the state as a force standing above society to guarantee that all members of society behave like owners of private property. However, the state must be a discrete, independent force, since it has to compel all members of society toShow MoreRelatedViolence Portrayed By The Media Essay1101 Words   |  5 Pagessurveys and publications to determine their findings. Although extensive research was conducted, the findings show that there is no long-term effect on young adults. This may be debated in years to come as social media is advancing so rapidly. In Timmer’s article, his research includes data dating back to 1934 when The Motion Picture Code had film restrictions such as crime and sex (29). Although these restrictions were not totally enforced, The Motion Picture Production Code was forced to take different