Lupine Publishers| What’s So Positive About Positive Psychology and Looked After Children

 

  Lupine Publishers | Journal of Health Research and Reviews

bstract

The work with Looked after Children appears to be focused mainly on their past difficult life experiences. This article is trying to address this over-simplification and reflect on the implications regarding therapy

Introduction

The concept of looked after children was introduced by Department of Health within the Children Act 1989. It describes all children in public care; i.e. children in foster and residential care and children that live with their parents but are subject to care orders. It is estimated that more than 5 children and young people per 1000 under 18 years of age in England are looked after (Department of Health, 2001a; DCFS, 2009). There are indications that these numbers are increasing (Department of Education, 2010) Some evidence (McCann et al. [1]; Scott [2]; Utting et al. [3]) indicates that 56% of looked after children have significant psychological difficulties and that 45% of looked after children present difficulties that can be recognised as mental health (psychiatric) disorder. This is more than four times the number that would be expected in the general population. However 44% of looked after children do not present significant psychological problems and 55% do not present a psychiatric disorder. This more positive statistic is impressive but rather ignored one in the context of the difficult and traumatic developmental background of these children.

Why Are Children Looked After?

Looked after Children are in care because their parents are not available or not able to care for them. However the complete picture regarding their pre-natal, post-natal and childhood experiences is not always fully understood by the general public and regrettably sometimes by the professionals. Whilst the sensational and shocking facts of the most extreme cases, often involving physical and sexual abuse or extreme neglect, reach the public arena through the media, there appears to be less awareness of emotional neglect and the subtler psychological and physical deprivations that may have a dramatic effect on children’s physical, emotional, cognitive and social development. In particular there is lack of awareness of the pre-natal and post-natal factors (Linnet et al. [4]; Szyf et al, [5]). Those include genetic factors, influences on both the health of the mother and her foetus during pregnancy and the physical and care environment after birth (Evans [6]; KimCohen, et al. [7]). In addition people’s choice of partners may not be completely random (Rushton et al. [8]; Rushton & Nicholson [9]). Indeed in animals it has been shown that epigenetic factors can influence choice of partners (Crews et al. [10]). Propensity for genetic disorders in certain populations may be higher than in other populations (Dohrenwend et al. [11]). In some populations pregnant mothers are more exposed to drugs, alcohol, poor diet, violence; etc (Anderson [12]; Williams & Collins [13]). Many babies are born into environments that are unsafe, unhygienic, unhealthy, neglectful, inconsistent, threatening; parents may lack sufficient parenting skills and be mentally challenged (Belsky et al. [14])

The Sad Story

The past of a looked after child could be described as a sad story however there is more to the sad story than meets the eye. This story of difficult and tragic childhood experiences started to be written before it began to fully unfold, determined by the genetic and prenatal factors already mentioned (Gluckman & Hanson [15]). What chance do these children have with this kind of genetic and experiential background? It would be reasonable to assume that they are all doomed to life of dysfunction, dependence and misery. However many of them defy this expectation. We are still in the process of learning about the protective and other factors that make the difference (Cocker & Scott [16]; Masten & Obradovic [17]; Murowchick [18]). For example, the quality of relationships with foster caregivers appears to be a very important factor in children’s’ abilities to regulate emotions and cope with stress and challenges. (Oosterman et al. [19]).

The more we learn the more we are inclined to think that some people become positive, successful and well functioning not in spite of their difficult background and experiences but because of them.

From Repairing the Sad Story to Building on the Sad Story

The sad story has already been written. It belongs to the past and the past cannot be changed. We live always in present and any moment in life defines its present. It is those moments of ‘present’, the ‘here and now’ that provide us with the opportunity for change Bishop et al. [20] It is important to have the opportunity to change our stance towards the past and changing our plans for the future. This of course depends very much on whether we are willing and able to take this pro-active stance. If not, we are at the mercy of our sad story and this will dictate to large extend what we think, feel and do (Langle & Sykes [21]). Many of the children who are looked after, regrettably, are either not aware or not able or both, to take a stance towards their past. What is even more tragic is that many professionals are the same in this sense. There appears to be a shared and mutually reinforcing approach that the past explains and is responsible fully for, what happens now and how it defines the future. This approach is very much reinforced by a deterministic view of psychology and behaviour; e.g. Freud (Wallwork [22]) and from the other side of the theoretical spectrum: Skinner (Skinner [23]).

Humanistic Psychology provides us with the opportunity to view the person from a non-pathologising perspective (Clay, 2002). Rollo May and Carl Rogers emphasise the human ability to make choices and self-direct their behaviour. The Existential Psychology approach focuses on the way people deal with the givens of their existence and what there are (Yalom, 1980). Victor Frankl for example promotes people ability to create meaning as a way to cope with uncontrollable and un-avoidable facts of existence (Frankl, 1997). In this way both Humanism and Existentialism created a picture of a human being as able and even responsible for determination of their stance and behaviour. In more than one sense Humanistic and Existential Psychology could be seen as forerunners of Positive Psychology movement. It appears that these approaches have not yet made significant enough impact on work and intervention with Looked after Children.

From Repairing the Worst Things in Life to Building the Best Qualities in Life

Most (but not all) of therapeutic work with looked after children tends to focus on the factors that have detrimental effect on the client’s wellbeing and behaviour. There appears to be an emphasis on ‘repair’. If only, through interaction with the client (discussion, play, rapport and interpersonal relationship), we would ‘fix’ those destructive and detrimental factors than we would help the client on his/her road to recovery. There are at least four big questions related to this kind of approach: Is it actually possible? (Can we as yet manipulate the hereditary factors; can we change what has already happened in the past)? Even if it is possible, do we not face the danger of destroying those hereditary ‘negative’ and experientially painful elements that have the potential to promote personal uniqueness, specific talents, creativity, excellence, achievement motivation; etc. (Levita [24]) Do we, by focusing on the factors that make us unhealthy, dysfunctional, unhappy; etc. unintentionally promote the clients’ sense of vulnerability and helplessness, as well as our perception of the clients’ vulnerability and helplessness? Do we, through the focus on the past and the time spent in therapy prevent exposure to, and potential positive effects of, present experiences? The Positive Psychology approach shifts the emphasis from fixing what makes us unhealthy to exploration and utilisation of factors that make us healthy (Seligman & Csikszentmihalyi [25]), providing a guiding light to possible change in the emphasis of therapeutic work and intervention with children who are looked after (Houston [26]; Kalke, Glanton, & Cristalli [27]; Snyder and Lopez [28]; Linley and Joseph [29]; Joseph and Linley [30]).

More recent articles argue for the integration of Clinical psychology and Positive Psychology; e.g. (Johnson and Wood [31]) and provide evidence of the efficacy of using Positive Psychology intervention methods; e.g. (Chavez et al [32]; Roth, Suldo & Ferron [33]). The concept of Therapy for Looked after Children itself is challenged if we are to be open to the ideas from positive psychology. Promotion of scholastic achievement is one such concept. Provision of daily experiences that promote happiness and wellbeing; training for work and vocation; promoting civility, kindness and altruism; supporting special talents, are only some of the other challenging ideas [34]. Other ideas are not necessarily alien to Therapy but provide shift of emphasis; e.g. promoting resilience, self efficacy and optimism as well as helping to develop positive personal traits; e.g. courage and interpersonal skills [35]. And finally a concept that in the spirit of this paper may be the most important: promoting the functional aspects of personal uniqueness

Conclusion

The intention of this paper is not necessarily to overthrow the traditional approaches to therapy but to reflect on a radically different way of thinking about therapy aims and methods [35]. Neglecting completely the traditional methods would not sit easy with the conceptual framework of positive psychology that would, by and large, promote diversity of thought and ideas [36]. However, it challenges the idea that the sad story produces a broken child that we need to fix; rather it suggests that the past, however traumatic, and the genetic load, however specific, contribute to our own uniqueness and diversity of being and that by focusing on that which is healthy, the therapeutic process can facilitate the individual child in finding their own pathway to a more positive future [37].

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Lupine Publishers|Becoming an Erudite of Nursing Profession in the 21st Century: The Career Path

 

  Lupine Publishers | Journal of Health Research and Reviews

Introduction

A career is a lifelong commitment that has the potential to be extremely rewarding and not merely a pay check. It is therefore important for anyone wishing to choose a career to carefully consider all aspects of the career. The aim of this paper is to show the career path to becoming an erudite in nursing profession in this 21st century. According to the Oxford Advanced English Dictionary, an erudite is someone who have or shows profound knowledge to have learnt or scholarly in his or her chosen field. It is a most distinguishing level or status that is earned, attained and not through any man’s generosity. This is made possible by hard work, mentoring, sacrifice, maintaining the highest standards of excellence and achievement, appropriate studying until one is approved, been extremely strong emotionally and physically in order to stand-out. However, it must be quickly resolved here, that as mortals, we are limited in certain rights. No matter how a man tries, except God puts His blessings upon Him, he may just be labouring in vain. The path to becoming an erudite in a chosen field like nursing starts from career advancement/development.

Career advancement in nursing constitutes any form of professional promotion that recognizes and rewards talent in clinical and administrative nursing practice. It serves as a tool that supports nursing excellence through the conferment of higher clinical status to those nurses who meet the requirements [1].

The Professional Excellence and Career Advancement in Nursing (PECAN) model emphasized mentorship and self-efficacy as major determinant of professional development and career advancement of clinical nurse leadership [2]. The model proposes that nurses who are self-efficacious and receive appropriate mentoring are better positioned to engage in ongoing professional development as well as pursuing and acquiring a higher level of education. As nurses attain higher level of professional preparedness, they are in a better position to optimally leverage the competencies and factors identified in the model (external support, human capital factors, social capital factors and system factors) to advance their career, enhance and develop their leadership skills and improve positive patient outcome as well as proffer solutions to problem arising in health care delivery system. A nurse who will be an erudite in this 21st century must understand personal branding. Personal branding asks the question of what is unique about the individual. This means that personal branding breaks the individual from others by telling everyone who you are, what you do, how you do it and what makes you different from everyone else. In other words you create value and benefit in a way that no one else can. As a direct patient caregiver, the nurse ensures that his brand is directly related to the quality or value of your patient care and skills. Through branding the nurse establish a value and as result establish trust.

A nurse who chooses to be an erudite and make impact in his/ her own chosen field must:

a) Live by the tenets of the profession as contained in the Nurses Pledge (Florence Nightingale Prayers).

b) Have good organizational skills and be able to choose the right association that focuses on topics that will help in building him/her.

c) Have strong communication skills: Develop relationships by sharing information, knowledge and insight with a variety of other medical professionals, patients or the population in general.

d) Set a career and a job goal: Develop a road map for the job and career success. One cannot be successful in a career or profession without setting both short-term and long-term goals.

e) Innovative: Instead of waiting for change to find you, continuously bring innovation into your job and to stay ahead of it. Take the initiative with ideas for doing things better and have the courage to advance and implement the

f) Choose skills and not title: Think of your career in term of building blocks with each block representing a set of skills. Do whatever it takes to acquire the skill that will help take you to the next level.

g) Be ready to boost skills through exploring new education/ training opportunities.

h) Focus on time efficacy: Spend time on activities that are enlightening and productive. Sooner than later, there will be gained hours to reap the benefits of success. Dedicate time and effort to determining the plan for your preferred future and execute that plan in focused and consistent manner.

Conclusion

The 21st century poses a lot of challenge for practitioners of nursing who is expected to successfully engage in health care policy development and decision making. The development of a critical mass of nurse leaders who will be in the front-line of practice as well as in formal administrative roles cannot be apt than this time [2]. Educational system and policies must be designed in such a way that will make the emergence of erudite easier in which the knowledge, facts, skill which is important in nursing as a profession. The educators should be adequately qualified to impact the adequate skills and knowledge needed by the students to become erudite of the profession. The main task of becoming an erudite depends greatly on the students in aspects of personal reading, research and improvements of their skills with clear evidence of show of interest in the profession. The financial, spiritual and psychology support from the parents cannot be over-emphasised.

The primary goal of nursing is to improve the overall health and well-being of entire population’s at all levels of health care. The potential place of employment for nurses ranges from government agencies to private businesses. The nurse is expected to work, develop and implement plans that work on promoting, and reducing various health and safety within the population they serve. Nurses differs from other health providers in that they don’t simply care for a single patient at a time but for the family and spend the longest hours of the day with the patient. We must look beyond just obtaining a degree and caring for patient in order to take ownership of our professional development and career advancement within nursing and among the multidisciplinary team. The contemporary nurses constantly face series of technological, managerial, administrative, political and economic changes involving new ideas, new values and new problems that may need on the spot decisions and solutions [3]. It is therefore obvious that contemporary nurses need a new orientation to help them successfully cope with developing changes in the health care to attain the erudite status accrued over long and sustained career development. Nursing is amongst the most sought-for careers in life [4]. Be proud therefore that you belong to this most celebrated, cherished, down-to-heart, non-profit making, selfless and divinely career called-NURSING.

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Lupine Publishers| Development of a Pulse Measuring System for Healthcare

 

  Lupine Publishers | Journal of Health Research and Reviews

Abstract

Mobile health care monitoring provides easy assessment of patient’s health status by looking at the changes in vital sign. The health care giver can have access to this data. In this work, a mobile heart rate monitoring system is implemented. In order to detect the heartbeat/pulse. The device works with an android application which receives the data and sends the gotten data to the health care giver. The system makes use of arduino board which functions as a microprocessor. The pulse sensor takes in the pulse readings and the arduino uno micropocesssor converts it to heartbeat via series of programmed instructions on the microprocessor.

Keywords: Mobile; Heart rate; Vital signs; Arduino

Introduction

Mobile system brings patient closer to the doctor therefore bringing about a better awareness between the patient and doctor and equally reducing the stress and long manual way of patient having to visit the doctor often. It equally brings about efficiency in health care Andreas et al. [1].

Vital Signs

Vital signs are indicators of patient’s health status. Some of them includes: temperature, pulse, respiration and blood pressure (BP)and pulse oximetry. They are useful in detecting or monitoring medical problems. Vital signs and other physiological measurements can be the bases for problem [2]. The normal ranges of the vital signs are finely adjusted, and any deviation from normal may indicate disease. During the course of an illness, variations in the vital signs may occur and this may indicate changes in the patient’s condition.

Pulse Rate

The pulse rate is a measurement of the heart rate, or the number of times the heart beats per minute. As the heart pushes blood through the arteries, the arteries expand and contract with the flow of the blood. Taking a pulse not only measures the heart rate, but also can indicate the following: Heart rhythm Strength of the pulse [3,4]. The normal pulse for a healthy adult ranges from 60 to 100 beats per minute. The pulse rate may fluctuate and increase with exercise, illness, injury, and emotions. Females ages 12 and older, in general, tend to have faster heart rates than do males. Athletes, such as runners, who do a lot of cardiovascular conditioning, may have heart rates near 40 beats per minute and experience no problems.

There is a need for a heartbeat monitoring due to the fact that the heart happens to be one of the most vital organ in the human body hence it functionality is of vital importance to anyone [4,5].

Design of the Proposed System

The proposed mobile health pulse monitoring system is meant to help in the effective monitoring of heart beats changes in the human body of a patient (as this is crucial to the health state of the patient) , hence keeping the patient updated about their heart health and making the health care giver aware of the functional state of the patient which in turn gives the doctor an updated information about a patient and the progress in their health [6,7]. The systems which consist of a heart beat measuring device (built with an arduino board) with an android application serves as an interface of communication between the patient and the health care giver hence sending the data in form of a Short Message Service (SMS) to the doctor [8,9]. The system hardware part is built with an arduino board which serves as the microprocessor, this processor has other hardware components which are connected to the board and all these are equally attached to the Vero board. These attached devices are programmed to be controlled by the microprocessor (Arduino).

Pulse Calculation

There are various means which pulse beat per minute of an individual could be gotten different method could be used all depending on the calculation method one choses to adopt.

In this method we have to read only five pulses. Then we calculate the total heart rate in minute by applying the model below

Five_pulse_time =time2 – time1;

Single_pulse_time = Five_pulse_time / 5;

Rate = 60/ Five_pulse_time;

Where time1 is the first pulse counter value and time 2 is the last counter value. Rate is the final heart rate.

When the first pulse comes the counter is started, by using timer counter function in arduino that is millis ( ); and take first pulse counter value form millis( ); Then wait for five pulses. After getting five pulses, again take the counter value in time2 and then subtract time1 from time2 to take original time taken by the five pulses. And then divide this by 5 times for getting single pulse time. Now that we have time for single pulse and we can easily find the pulse in one minute, dividing 60second by single pulse time [10,11].

Rate = 60000ms / single pulse time (Figure 1).

Figure 1: Initial implementation of the device.

Implementation

Hardware Mobile Device Implementation

Figure 2 above shows the step taken to using the system, which involves placing the fore finger on the pulse sensor. However, one needs to use a support aid as we make contact with the system, which is meant to help maintain fixed contact with the finger so as to ensure accurate pulse readings. Display of a value of pulse reading from my device. Hence this hardware device measures the pulse rate per minute and displays the value on a screen which makes it accessible by the user (Figure 3). This device has a bluetooth module which makes it easy for the device to connect with the patient android device hence transferring the readings to the phone applications [12,13]. This data is the transfer to the health care giver mobile number in form of a message which contains the beat per minute and location.

Figure 2: Taking of pulse reading from sensor.

Figure 3: Display of a value of pulse reading from my device.

The Software Platform

The software application this data helps in the transfer of data gotten from the monitoring device this helps to transmit the data from the application to the doctor’s phone in form of a message at the click of the send data on the application by the patient (Figure 4). From the result gotten of test carried out on different people, it can be seen that the result varies, which shows the varying heart beats of different people and how it changes from person to persons (Figures 5 & 6). We got a value between ranges of heart beat from 60bpm to 100bpm for normal healthy persons, but for an athlete due to often exercise and training it is between the values of 155 bpm to 174 bpm. The ABNORMAL value gotten is from a person who was sick giving us a value between 175bpm to 151 and 160 bpm to 151 bpm [14] (Figures 7 & 8). The test was conducted on different healthy people and on an athlete and two sick people. From the result it can be concluded that the normal people have different heart beat readings which could be affected by their health states. The result has helped us to conclude and know the different readings and changes in the human heart beat. Hence providing us with accurate knowledge and values as shown in the (Table 1) and (Figures 9 & 10).

Figure 4: Heartbeat device.

Figure 5: Application Lunching.

Figure 6: Data accepting interface of the application.

Figure 7: Sample case1 data received on the application.

Figure 8: Sample case2 data received on the application.

Figure 9: Sample case3 data received on the application.

Figure 10: Sample case4 data received on the application.

Table 1: Test Result Analysis from Some Samples.

Conclusion

This work has been able to help in the development of a mobile pulse monitoring system, which is for the purpose of determining the heartbeat (Figures 11 & 12), it helps to monitor effectively the different changes in the heart beat of a user and it notifies the medical agent about the gotten data, hence keeping the medical agent updated about the internal changes or health status of the patients. The project was executed with the use of a microprocessor (arduino uno) and other hardware components like the sensors, Bluetooth module (Figures 13 & 14).

Figure 11: Test case sample 5 for an athlete data, received on the application.

Figure 12: Test case sample 6 for an athlete data, received on the application.

Figure 13: Test case sample 7 for a sick person, data received on the application.

Figure 14: Test case sample 8 for a sick patient, data received on the application.

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Lupine Publishers|Digitoxin has Specific Properties for Potential use to Treat Cancer and Inflammatory Diseases

 

  Lupine Publishers | Journal of Health Research and Reviews

Abstract

New knowledge about diseases on the molecular level demonstrates that inflammation is a common determinant for seemingly very different disorders. Long standing high levels of pro-inflammatory cytokines is an important factor also for cancer. In fact, the pro-inflammatory cytokines may stimulate normal cells, such as immune cells and fibroblasts, to produce more growth factors and cytokines that the cancer cells take advantage of and a vicious circle occurs. More focus is now on this interaction in cancer research and how to break it. Pancreas cancer is a typical example with a lot of stroma in relation to the cancer cells. Cardiac glycosides, especially in the form of digitoxin, have very interesting properties when it comes to target these mechanisms on the molecular level.

Keywords: Cardiac Glycosides; Digitoxin; Apoptosis; Cancer; Pancreas; Glioblastoma; Cholangiocarcinoma

Abbreviations: NK: Natural Killer, PD-L1: Programmed Death-1-Ligand, CNS: Central Nervous System, EGFR: Epidermal Growth Factor Receptor, NF-κB: Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells, CAFs: Cancer-Associated Fibroblasts, TGF-β: Transforming Growth Factor Beta, IL-6: Interleukin-6, TNF-α: Tumor Necrosis Fac

Introduction

The innate immune system plays a pivotal role for eradicating cancer cells in humans. Apoptosis (programmed cell death) in cancer cells triggered by immune cells, such as human NK cells, is a mechanism for the human body to get rid of malignant cells [1]. During studies how to strengthen the innate immune system against cancer we found that cardiac glycosides, digoxin and digitoxin, are potent inducers of apoptosis in different types of cancer cells in doses that are not toxic for humans. Actually, we were the first to show apoptosis in cancer cells by digitalis [2,3]. The last years several new molecular modes of action of the cardiac glycosides of impact for cancer and inflammatory diseases have been shown. Clinical studies of digitalis for cancer are ongoing and in progress, however, almost all use digoxin [4]. Our data indicate that digitoxin has more potent anti-cancer effects, in concentrations that are non-toxic for humans, than digoxin [2-6]. Digitoxin is of interest to use as single agent and in combination with chemotherapy in clinical cancer trials and may also be valuable to suppress harmful inflammatory reactions. Digitoxin may also be combined with radiotherapy and/or new antibodies, such as PD-L1 antibodies, to enhance the anti-cancer effects. This mini-review summarizes some of the most interesting properties of the cardiac glycosides from a clinical point of view.

Background

William Withering made digitalis a common drug to treat cardiac congestion by his book. ”An account of the Foxglove and some of its Medical uses with practical remarks on the dropsy, and other diseases”, published in 1785. Digitalis extract had been used in folk medicine much earlier, but Withering’s observations led to a more rational use. Plant extracts containing cardiac glycosides, for example from Nerium Oleander, have been documented in remedies against cancer as early as in the Middle Ages from different parts of the world [3]. Today digitalis, in the form of the cardiac glycosides digoxin and digitoxin, is used to treat cardiac congestion and some arrhythmias, however, the use is decreasing and digitoxin has been taken off the markets in many countries as it has been replaced by other cardiac drugs. Generally, digoxin is regarded easier to dosage than digitoxin and digoxin has been more common to use than digitoxin. Digoxin has a shorter half-life than digitoxin. The chemical difference is that digoxin has an extra hydroxyl group (-OH) compared to digitoxin; i.e. digoxin is more hydrophilic and is excreted by the kidneys. Digitoxin is mainly metabolized in the liver and excreted by the faeces. Digitoxin is lipophilic and pass the blood-brain barrier and reach the CNS and higher than plasma concentrations in the liver, kidneys, brain and heart [3]. The renal function has a” normal decline” by increasing age, in contrast to liver function, and most patients with cardiac congestion are older, thus, digitoxin may be safer in this patient population [7]. Recently, a debate among cardiologists has started; maybe digitalis has been replaced too early by newer drugs. Studies comparing the newer cardiac drugs to digitalis are lacking [8]. Digitalis has the unique capability to increase the inotropic effect of the cardiac muscle without increasing the oxygen consumption. Interestingly, healthy volunteers taking digitoxin in therapeutic dose for treating cardiac congestion, had reduced diastolic blood pressure and heart rate during overnight sleep, probably because of increased parasympathetic activity or decreased sympathetic activity [9]. Time will show if digitoxin will have a renaissance in cardiology.

Properties of Cardiac Glycosides Pivotal for Cancer and Inflammation

Jens C. Skou made the first discovery of an ion-transporting enzyme, the ubiquitous plasma membrane Na+/K+ ATPase in 1957. The main pharmacological effect of clinical benefit of the cardiac glycosides seemed to be inhibition of the Na+/K+ ATPase on cardiac muscle cells and the subsequent ion changes with increased intracellular calcium ion concentration leading to a positive inotropic effect on the heart. Since we reported apoptosis in cancer cells by cardiac glycosides, it has become obvious that the Na+/ K+ ATPase have two distinct roles; the well known as an ion pump and in addition as a protein-protein signal transducer. Increased intracellular calcium ion concentration is a part of the apoptotic cascade and in addition the Na+/ K+ ATPase signals through several other signaling pathways that regulate apoptosis and proliferation, such as through the pathways of EGFR and other tyrosine kinase receptors [10]. Notably, digitoxin is a strong inhibitor of the transcription factor NF-κB and can abolish the production of proinflammatory cytokines [11]. The tumor micro-environment and stroma directly influences the progression of solid tumors through secretion of growth factors and extracellular matrix depositions. CAFs support angiogenesis and cancer cell invasion and metastasis. TGF-β from cancer cells start differentiation of fibroblasts to CAFs. This mechanism seems to be present for different types of solid tumors, such as glioblastoma, pancreas cancer, prostate cancer and also for several hematological malignancies. Pro-inflammatory cytokines such as IL-6 and TNF-α are often involved in this interplay between the cancer cells and stroma cells as well [12-15]. Cardiac glycosides have the ability to inhibit this process [11,12,16]. The capability of digitoxin to inhibit NF-κB and by that abolish the pro-inflammatory cytokines, may be useful for an array of chronic inflammatory disorders such as ulcerative colitis, Crohn´s disease, systemic sclerosis among other diseases. However, real high levels of the pro-inflammatory cytokines may be acute life threatening. The bird flu virus, H5N1, killed many young healthy adults with intact immune systems. The main cause of death of these individuals were respiratory distress caused by a “cytokine storm”, hyper-production of pro-inflammatory cytokines; the immune system overreacted towards the virus [17,18]. It was great concern during the H5N1 epidemic how to handle the situation as the accessible antiviral drugs were not very effective. It would be worthwhile to evaluate digitoxin in this context if such a situation occurs again and we do not have any other effective drugs.

Digitoxin makes the cancer cells immunogenic, especially in combination with some type of chemotherapy [19,20]. The immunogenic effect of digitoxin as well as the inhibition of IL-6 and similar pro-inflammatory factors may make digitoxin an effective combination with newly developed PD-L1 antibodies [21]. In addition, we and others have shown a radio-sensitizing effect of cardiac glycosides on cancer cells [3]. Naturally, one wonder if all these interesting molecular effects of the cardiac glycosides are clinically relevant. Epidemiological studies may give some indications. We examined a population of more than 9000 patients on digitoxin for cardiac disease and correlated to data in the Norwegian Cancer Registry. This population has serious cardiac disease and eventual anti-cancer effects may be masked behind the high morbidity and mortality due to the cardiac conditions. Still, significant anti-cancer effects were detected for leukemia/lymphoma and urothelial and kidney cancer [22]. Several epidemiological studies on digitalis and cancer have been done, most concerning digoxin, and the results differ considerably. Some studies find anti-cancer effects, others not, some studies indicate an increased risk for cancer in a population on digitalis [23-25].

It has been hypothesized that the anti-cancer effect of digitalis is due to an estrogen effect and that this estrogen effect also could increase the risk for some cancers [26]. However, in our experiments we found estrogen expressing breast cancer cells to be less sensitive for digitoxin compared to receptor negative breast cancer cells [3]. Recent data confirm that mechanisms other than interaction with hormone receptors are the main effect of digitalis on breast cancer cells [27].

Digitoxin has complex dose dependent mechanisms of action; lower concentrations may induce transcription of survival genes whereas higher concentrations can induce cell death by caspase activation and apoptosis and even higher concentrations induce cell death through necrosis due to heavily disrupted ion homeostasis. Digitoxin seems to target several signaling mechanisms of crucial roles for cancer cells simultaneously and that might make it more difficult for the cancer cells to develop resistance [3,10].

Conclusion

Despite the vast number of in vitro studies, epidemiological studies and clinical cancer studies done the last 10+ years, still we do not know if any cardiac glycoside will have a role in oncology. Most of the clinical studies so far are on digoxin and a few other cardiac glycosides, however, digitoxin seems most promising as an eventual anti-cancer drug. Considering the molecular modes of actions and pharmacokinetics of digitoxin; glioblastoma, pancreatic cancer, leukemia/lymphoma, kidney cancer, urothelial carcinoma and cholangiocarcinoma are some of the most interesting types of cancer for digitoxin treatment. Digitoxin can be combined with chemotherapy, immune therapy and radiotherapy in these clinical trials.

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Lupine Publishers: Lupine Publishers | Abundance, Generation Determin...:   Lupine Publishers | Current Investigations in Agriculture and Current Research Abstract The present work was...