Tyranny of the Weak: North Korea and the World, 1950–1992

Author: Charles K. Armstrong

Few books have accurately described the internal mechanisms that drive both the domestic and foreign policies of North Korea. This has led to a pervasive perspective in the West that North Korea is a ‘hermit kingdom’ which seeks to insulate its domestic population from external influences while simultaneously advancing a foreign policy that supports a political system which aims to hold back superpowers from interfering with its internal affairs. Fortunately, Professor Charles Armstrong of Columbia University has written an excellent book, Tyranny of the Weak: North Korea and the World (1950–1992), which demystifies the internal workings of North Korea while concurrently succinctly explaining the reasoning behind the policies formulated by the political leadership of the communist state.

In the beginning of the book, Professor Armstrong points out that fissures do exist in the international system due to the persistence of periodic conflicts in certain regions as further expounded by the following statement:

“Certain places in the world act as fractures in the international system, points of contact between the tectonic plates of historical change that erupt periodically into conflicts that spread beyond the region to draw in the Great Powers, and which remain in constant tension even in times of relative peace.”(p.1)

He then goes ahead and names the Korean peninsula as a region which has experienced a perennial conflict which has drawn the major global superpowers into confrontation. The author then goes ahead to point out that there is a certain lack of understanding of how North Korea operates within the international system since the policy formulators, politicians and other concerned parties responsible for foreign policy formulation and implementation have an inadequate comprehension of the internal mechanisms and processes which operate the political system in North Korea.

A critical reading of Tyranny of the Weak will enable the reader to decipher the principal intentions which motivated Professor Armstrong to write the book. The chief motivator for Professor Armstrong was to demystify the perception that North Korea as an impenetrable system whose inner workings were incomprehensible (p. 4-5). This pervasive belief is informed largely by the fact that the actions of the North Korean government have either been provocative, irrational, unpredictable or sometimes suicidal (p.8). In the book, Professor Armstrong explains the motivations which lead the North Korean political establishment to create the processes which guide their overall operations; and what were the effects of these processes on the foreign policies which guided the establishment of foreign relations for the communist state especially during the era of the Cold War (p.9).

It is common knowledge that the value of a book is contingent on the authenticity and veracity of the information it contains. Since information pertaining to North Korea is particularly hard to come by inside the communist state (p.7), and the available information in the public domain is either relatively scarce or polluted by propaganda and disinformation (p.65); Professor Armstrong decided to collect and collate his information from archival sources. The main archives that professor Armstrong used in his extensive research when preparing the book are the archives of both the present and former allies of North Korea including China, the former Soviet Union, East Germany and other Eastern bloc countries (North Korea itself rarely declassifies its information pertaining to foreign policies or military affairs). Also, the author has drawn information from the central NKIDP (North Korea Independent Documentation Project) and when deemed appropriate, he has conducted interviews with the relevant parties (p.7). Most of the archival data was written by members of either the state security or the foreign ministry who had interactions with the North Korean leadership; and as such their veracity is confirmed. This is truly remarkable since it ensures that the book contains accurate, verifiable and authentic information. Moreover, the information contained in the book is actionable, that is, it would enable policy formulators to understand North Korea and thereby formulate the appropriate policies which will guide engagement with the dictatorial political leadership.

The author explains in detail how the communist country has been able to manage its foreign alliances (especially with communist countries p.55) while still maintain a precarious independence during times of political ambiguity (for instance, during the Sino-soviet conflict p.99) and also how it presents itself to the world as a model for development for low-income nations (p.59).  

In chapter one, the author describes how the Unfinished 1950-1953 war shaped the political discourse in the Korean Peninsula when the two Koreas divided by both political ideology and foreign alliances entered into a ‘hot conflict’ after North Korea (with soviet assistance) invaded South Korea. The author depicts the political thinking of the soviet leadership regarding the possibility of War in the Korean Peninsula by quoting Joseph Stalin who said:

“If a war is inevitable, then let it be waged now, and not in a few years when Japanese militarism will be restored as an ally of the USA and when the USA and Japan will have a ready-made bridgehead on the continent in the form of the entire Korea run by Syngman Rhee.” (p.10)

The above quote does show that North Korea had implicit Soviet approval to invade South Korea, and this approval was informed by the fact that the communist bloc nation viewed the then simmering Korea conflict within the context of the Cold war (p13). Initially, North Korea successfully conducted the war, and it was even able to occupy Seoul, the capital of South Korea (p.25). However, the United States was able to mobilize the non-communist world under the banner of the United Nations to come to the assistance of South Korea which at that time was on the edge of military defeat. The US and its allies were able to push the communists out of South Korea and into North Korea proper, and this led the communist leadership to ask for military assistance from its allies (p.42). Strangely, as the author point out, it was china which came to its assistance and not the Soviet Union as the North Korean had initially expected. With China’s entrance into the conflict, the UN forces were forced out of the lands they had occupied in North Korea and subsequently pushed back to initial border of the two Koreas (p.52). According to the author, this military collaboration between China and North Korea is what informed the North Korean leadership to maintain a policy of diplomatic ambiguity during the Sino-Soviet split as they did not want to lose soviet patronage while at the same time they did not want to antagonize China since it had helped them survive the Korean War (p.111). Moreover, this ambiguity was informed by the fact that the communist leadership did seek to maintain their precarious independence and also avert catastrophic leadership crises as this would allow them to form strategic foreign alliances when necessary (p.101), for instance, this ambiguity enabled North Korea to create formal foreign diplomatic relations with the non-aligned members of the Third world to which North Korea depicted itself as a model nation (p.143, p.178). Moreover, the author explicitly stresses that the experiences of the Korean War did mould the processes adopted by the North Korean regime to guide and control its internal system of power and its external affairs (p.179).

The author also describes how the political leadership of the DPRK (Democratic People’s Republic of Korea, North Korea official name) has been able to both covertly and overtly attempt to reach out to the capitalist Occident while concurrently confronting and engaging with its enemies (especially the United States and its ally in the Korean peninsula, South Korea) (p.276). The author shows that this necessity has been informed by the fact that DPRK has been faced by a myriad of opportunities and challenges such as fluidity in its foreign relationships, catastrophic famines, economic isolation, breakup of the Soviet Union, South Korean economic miracle, china’s state-controlled economic liberalization and attempts of rapprochement by the Western nations. Moreover, DPRK has been trying to normalize its relationship with international bodies, and for this reason it has been forced to de-escalate the Korean Nuclear crisis by destroying some of its own nuclear assets (p.280).

Professor Armstrong clearly explains in the book how the DPRK has been able to survive foreign invasions, famines, global calamities and the fall of the Soviet Union with its political leadership still remaining intact while concurrently maintaining the integrity of its internal social harmony (p.292). The author states that North Korea has been able to obtain maximum benefits from its dealing with foreign nations by applying a strategy christened ‘tyranny of the weak’ whereby its political leadership has been able to leverage the country’s objective weaknesses with its significant military resources (p.282). Upon reading the book, one will be able to learn that the North Korean policy of “self-reliance”, which was formulated in the 1950s and have been implemented since then, has enabled the nation to resist external pressure from both allies and enemies (p.279).

Professor Armstrong has done what other scholars who specialize in North Korea issues have been unable to do; describe how history has been used by the political leadership to maintain their grip of power in the nation while also maintaining social harmony. The author has also described how the two major conflicts that have affected North Korea (Cold War and the Korean War p.11) have shaped the worldview of the nation’s political leadership and in extension to both the domestic and foreign policies (p.292). This way, the author attempts to convince his readers that for one to understand North Korea, one must grasp the historical forces which have shaped DPRK; without which, the world will continue to deal erroneously with DPRK (p.293).

In conclusion, my personal reaction to this book is one of pure admiration and respect for the author due to his presentation of authentic verifiable facts in a comprehensible format using a vivid and capturing language. Honestly, this book demystifies North Korean by showing the reader that a lack of understanding of Korean history has led to a general lack of comprehension of the workings of DPRK, and therefore an understanding of Korean history will go a long way into enabling the reader to understand the motivations and intentions that guide the formulation of operational processes which are used to govern the nation by the DPRK leadership. This way, the book exposes the internal mechanisms of the DPRK to a wide audience.

Thymalin.

Introduction

Thymalin is an immunomodulator polypeptide derived from the thymus. This basic polypeptide is made up of 38 amino acids residues. Studies have shown that this immunomodulator molecule does occur naturally in the thymus. A summary of studies and findings concerning the functions on the thymus are described below.

Thymus

It is a specialized bilobed secondary lymphoid organ which is critical to the development of functionally active and self-tolerant T-cells. It is also a component of the adaptive immune system. Studies have shown that the actions of the thymus are mediated by immunomodulators.

In the thymus, the precursor thymocytes do develop into mature T-cells. The process of maturation involves recombination and rearrangements of the gene segments that code for the T-cell receptor. This leads to the development of unique peptide: MHC (Major Histocompatibility Complex) combinations of the receptor and this mediates central tolerance. These T-cell receptors mediate antigen recognition and antigen presentation. The mediation is occurs through interactions between epitopes of an antigen and the corresponding paratopesof the T-cell receptor.

The process of gene rearrangements is prone to errors which could lead to the development of either non-functional T-cells or T-cells which react strongly to self-antigens (autoreactive T-cells). To prevent these errors from occurring, the developing T-cells undergoselection based on their T-cell receptors affinity and specificity. Functional T-cells undergo positive selection and the autoreactive T-cells undergo negative selection. This occurs in the central medulla of each lobe of the thymus.

The mature T-cells eventually enter into the general circulation where they constitute the T-cell repertoire which mediates the functions of the adaptive immune system. Normally, the normal T-lymphocyte population is achieved early in life and this leads to involution of the thymusin early adulthood. However, loss (or sometimes complete absence) of the thymus before these population thresholds are reached results in DiGeorge Syndrome which is characterized by severe immunodeficiency.There is still residual T-celllymphopoiesis throughout the adult life. Nonetheless, studies have shown that complete involution of the thymus in old age is associated with increased susceptibility to severe infections and cancer development. This has been attributed to immune deficiency which impairs the immune response to infections and impairment of immune surveillance against tumors.

Other diseases associated with thymic dysfunction are allergic hypersensitivity, Severe Combined Immunodeficiency Syndrome (SCID), lymphomas, Myasthenia Gravis, thymomasand the rarity APECAD(Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy).

Thus, it is evident from the studies carried out on the thymus that the inductive environment provided by the thymus leads to the development of a functional, self-tolerant T-cell repertoire.

Thymic immunomodulators have the potential of restoring the integrity of thymic activity in a dysfunctional or diseased thymus, thus treating the associated immune deficiency or managing its severity. One of the most potent and efficacious pharmaceutical preparation of thymic immunomodulators is Thymalin.

Pharmacology of Thymalin

It is based on the principle that natural peptides have a significantly high potential of restoring normal biologic activity and are also associated with an acceptable toxicological profile. Studies have shown conclusively that the biologic activity is restored by the active component of the drug (the polypeptide constituent) while the toxicological profile is usually associated with the vehicle used.

In Thymalin, the active component is apolypeptide, and the vehicle used is a combination of water-soluble salts. Studies have shown that the immunostimulant effects of Thymalin are due to the capability of the polypeptide to modulate the ratio of the subpopulations of functional immunocompenent cells.

Specific studies

The studies which are reviewed below are known to have provided conclusive findings, and as such, their findings do have a bearing on the clinical use of Thymalin as an immunomodulator agent.

1.      Thymalin and thymus factor.

One of the earliest studies done on the immunomodulatory potential of thymicderivatives was done in 1982 by Pisarev et al in a study titled“Isolation, Physico-Chemical and Biological Properties of the Immunity Polypeptide Biomodulator from Thymus”. The study aimed at isolating a polypeptide fraction from the thymus which would be able to stimulate immunogenesis; and then evaluating its composition and its biological, physical and chemical properties in order to identify its corresponding thymic equivalent. The study used a multi-component extract which was subjected to fractionation procedures to derive three fractions labeled 1, 2 and 3, which were then analyzed for immunobiological activity. Also, the respective molecular masses and isoelectric potentials of the fractions were measured. The tyrosine contents of the fractions were also measured using the Lowry method. The results showed that fraction 1 exhibited no immunobiological activity. Fraction 2 and Fraction 3 both showed immunobiological activities, with fraction 3 showing a more efficacious immunostimulatory activity profile.  Fraction 3 was christened Thymalin and its conformational structure and properties elucidated. Thereafter, it was introduced into a culture of lymphocytes derived from pseudo-operated and thymectomized guinea pigs. The results showed a significant increase in the lymphocyte population derived from thymectomized guinea pigs, while there was no discernable increase in the lymphocyte population derived from the pseudo-operated guinea pigs. When thymus factor was introduced into a similar culture, the results obtained were similar to that obtained from Thymalin, and thus the study concluded that Thymalin is was indeed the thymus factor.

2.      Thymalin and Cervical Carcinoma.

In 1984, Dekster conducted a clinical study entitled “Clinico-immunologic changes in patients with cervical cancer after treatment with Thymalin” whose aim was to evaluate the beneficial effects of Thymalin on immunosuppressive states. In the study, 50 cervical carcinoma patients were evaluated. These patients registered low lymphocyte counts of variable severity before the administration of Thymalin. After Thymalin administration, the lymphocyte populations were measured and they were found to have increased significantly with the patients registering normal or near- lymphocyte counts. Thus, the results of this study demonstrate the need to includeThymalin in the management plans of cervical carcinoma.

3.      Thymalin and Endometrial Hyperplasia

In 1989, Zaporozhan et al conducted a study entitled “Effect of Thymalin on the immunological indices and morphofunctional structure of the uterus in guinea pigs with endometrial hyperplasia” which was aimed at evaluating the anti-neoplastic effects of Thymalin. The female guinea pigs studied numbered 125 in total, and the endometrial hyperplasia was induced by synestrol administration. The parameter used to monitor the progress of the indicated pathology was the lymphocyte population. This population decreased as the hyperplasia worsened. The administration of Thymalin in the diseased subjects resulted in the normalization of immune system indices (that is, restoration of the lymphocyte population to within the normal reference range), and partial restoration of the endometrial morphology.

Thus, from the above three studies, it can be concluded that Thymalin acts through the thymus to restore both the quantitative and qualitative capacities of T-cell lymphocytes. It also shows that Thymalin can be used in the management of various cancers.

Thymosin Alpha-1.

Introduction.

Thymosin Alpha-1 is a biologically active peptide derived from prothymosin-alpha. Current hypotheses consider Thymosin Alpha-1 to be the main constituent of Thymosin Fraction-5, and as such it is considered to be the active component that restores the immune function in both athymic animals and animals with dysfunctional thymus glands. Thymosin Alpha-1 was among the first peptide isolates of Thymosin Fraction-5 to be sequenced and thereafter synthetically synthesized.

In humans, the PTMA gene encodes prothymosin-alpha, a 113 amino-acid polypeptide. Thymosin Alpha-1 is a 28 amino-acid fragment of prothymosin-alpha, and research has shown that this fragment derivative enhances the cell-mediated immune component of the human immune system. Its immune actions have enabled it to be used for treating viral infections such as Hepatitis B and Hepatitis C. It has also been incorporated into vaccines as an immune booster. Clinical studies have also shown that Thymosin Alpha-1 can be used to manage neoplasias since they upregulate cytotoxic T-cells which are involved in immune surveillance.

Thymosins.

Thymosins are proteins with diverse biological actions. They are found in numerous animal tissues. They were originally isolated from thymic tissues, hence their name Thymosins. The main functions of thymosins are modulation and modification of biological responses. They are also known to stimulate leucopoiesis in the bone marrow. Leucopoiesis refers to the process of production of white blood cells from their stem cell precursors; and as such, endogenous thymosins do improve the immunocompetence status of an individual. Studies done on isolated thymic extracts have shown that two types of thymosins: Thymosin alpha-1 and Thymosin Beta-4 could be synthetically produced and then used therapeutically for immunostimulation and immunomodulation.

Thymosins were discovered in the 1960s as researchers sought to identify, categorize and study the biologically active humoral factors released by the thymus. The studies showed that some isolates from the thymus gland did restore immune functions while other isolates did not. These isolates were collectively termed as Thymosin Fraction-5. Further analysis of Thymosin Fraction-5 showed that it was comprised of about 40 peptides which were collectively termed as thymosins. Electric field studies were used to categorize these thymosins into alpha, beta and gamma fractions. Further molecular studies on the thymosin fractions showed that these fractions are genetically and structurally unrelated. Recent studies on thymosins have shown that thymosin beta-1 is ubiquitin. The studies also showed than thymosins can be produced by cells located outside the thymus. Research also showed that Thymosin alpha-1 administration did promote the differentiation of T-cells in athymic mice (that is, mice lacking the thymus). Thymosin alpha-1 has also been shown to have immune-potentiating actions that do interact with a dysfunctional thymus to reconstitute and normalize the immune status in children suffering from immunodeficiency.

The studies reviewed below have provided conclusive findings that demonstrate that Thymosin alpha-1 can be used clinically to improve the immune status.  

Selected studies.

The three studies reviewed hereafter have provided adequate and conclusive findings that Thymosin alpha-1 can be used clinically to manage cellular immunodeficiency.

1.      Thymosin Alpha-1 and Cellular Immunity.

In 1975, Goldstein et al published a study entitled “Thymosin Activity in Patients with Cellular Immunodeficiency” in The New England Journal of Medicine. The aim of this study was to investigate whether Thymosin alpha-1 increases the number of T-cell rosettes.

The subjects of this study were two groups of patients. One group suffered from primary immunodeficiency while the other group was affected by a viral illness. Lymphocytes extracted from these patients were incubated in-vitro with calf thymus extracts and sheep erythrocytes. The results showed that the T-cells populations increased until they reached their normal population after which thymosin had no further effect on them.

Thereafter, a female patient with primary immunodeficiency secondary to thymic hypoplasia was chosen to receive thymosin-α₁ in-vivo. Results showed that her T-cells rosettes increased by 33%. She also showed remarkable clinical improvement. However, she later on developed delayed-type hypersensitivity reactions to thymosin-α₁ extracted from calves.

This study therefore showed that Thymosin alpha-1 increases the number of T-cell rosettes in patients who have thymic hypoplasia. It also showed that thymosin-α₁ could be used to partially reconstitute the cellular arm of the immune system.

2.      Thymosin Alpha-1 and expression of lymphocytic interleukin-2 receptors.

In 1990, Kimberly D. Leichtling, Marcelo B. Sztein and Susana A. Serrate published a study entitled “Thymosin alpha 1 modulates the expression of high affinity interleukin-2 receptors on normal human lymphocytes” in the International Journal of Immunopharmacology. The aim of this study was to investigate the effects of Thymosin alpha-1(abbreviated in this study as Tα1) on high affinity IL-2R (interleukin 2 receptors). Peripheral lymphocytes derived from normal healthy human beings were used in this study. The results showed that Tα1 increased the population of high affinity IL-2R expressed by the lymphocytes. Likewise, it also increased Interleukin-2 production. Peak responses to Tα1 occurred when the Tα1 concentrations was 10⁻¹²M and 10⁻⁸M. Flow cytometry studies also showed that Tα1 upregulated Tac antigen expression.  However, it had no effect on the affinity of IL-2R for its respective ligands. Also, Tα1 demonstrated no effect in lymphocytes not subjected to mitogenic stimulation.

Thus, it can be concluded from this study that thymosin alpha-1 modulates the immune function by increasing the expression of Interleukin 2 and its corresponding receptors (IL-2R). Interleukin-2 (IL-2) is a cytokine that promotes lymphopoiesis, and it can therefore be inferred that the up-regulation of both IL-2 and IL-2R expression causes an increase in the T-cell population.

3.      Thymosin Alpha-1 and Chronic Hepatitis C.

In 1995, Rasi et al published their study under the title “Combination thymosin alpha 1 and lymphoblastoid interferon treatment in chronic hepatitis C” in the British Medical Journal. The aim of this study was to assess the effect on combination therapy on chronic hepatitis C. The combination therapy used was a twice weekly dose of 1mg thymosin alpha-1 and a thrice weekly dose of the lymphoblastoid-interferon, 3MU. The total number of subjects in this study was 15 chronic hepatitis C patients whose serum was positive for Hepatitis C Virus Ribonucleic acid (HCV RNA). 4 patients had failed standard interferon monotherapy and the rest were treatment naïve. All the 15 patients were treated with the combination therapy for 12 months and then subsequently followed-up for the next 6 months.

The results showed that 7 patients were HCV RNA negative after 6 months of combination therapy; and at the end of the treatment, this number had increased to 11 patients including 2 patients who had failed standard interferon monotherapy. During the follow-up period, 6 of the 11 patients showed a sustained HCV RNA negative status. It can therefore be concluded that this study showed that combination therapy of thymosin alpha-1 and interferon does provide potential benefit in the management of Chronic Hepatitis C disease.

In conclusion, the above three studies have shown that Thymosin alpha-1 partially reconstitutes the cellular arm of the immune system by increasing the number of T-cell rosettes in patients with thymic hypoplasia. It has also shown that Thymosin alpha-1 modulates the immune function by up-regulating the expression of IL-2 and IL-2R; and that it can also be used in the management of Chronic Hepatitis C.

Sermorelin.

Introduction.

Sermorelin is a GHRH (growth hormone–releasing hormone) peptide analogue. Its peptide sequence is comprised of 29 amino acids. This sequence is a portion of the endogenous human GHRH, and is currently considered to be the shortest synthetic peptide that possesses the full array of functional GHRH activity. Due to this fact, sermorelin is considered to be a growth hormone secretagogue.

Sermorelin has been used to stimulate the secretion of growth hormone from the adenohypophysis (also called the anterior pituitary). The anterior pituitary secretes trophic hormones. Sermorelin has also been used in stimulation tests to assess for pituitary sufficiency in relation to the secretion of the growth hormone.

Growth hormone–releasing hormone.

GHRH is 44 amino-acids polypeptide that stimulates the secretion of growth hormone from the adenohypophysis. It is also called somatocrinin or somatoliberin. It is produced in the cell bodies of periventricular arcuate neurons, and thereafter transported to the neurosecretory terminals of the neurons where they are released. The arcuate neurons do form part of the hypothalamo-hypophyseal portal system. Their release from the neurosecretory terminals occur in a pulsatile fashion and it thus follows that growth hormone (GH) release also occurs in a corresponding pulsatile fashion. GHRH binds to a secretin-type G-protein coupled serpentine receptor called the GHRH-receptor (GHRHR). Binding causes the receptor to activate both the cAMP (cyclic Adenosine Monophosphate)-dependent pathway and the phospholipase C (PLC) pathway. The terminal downstream actions of the cAMP-dependent pathway do upregulate the transcription of both the GH and GHRHR genes thereby providing a positive feedback loop that amplifies the production of GH. The GH produced is thereafter packaged in secretory vesicles. The downstream actions of the PLC pathway results in both Na⁺-voltage-dependent and Ca²⁺-dependent fusion of the secretory vesicles with the plasma membrane thereby releasing GH into the bloodstream.

The actions of GH ensure an optimal well-regulated post-natal growth. GH also promotes efficient energy metabolism. Studies have also shown that GHRH directly promotes slow wave NREM (non-rapid eye movement) sleep, and thus GHRH insufficiency causes a reduction in the amount and intensity of slow wave NREM sleep which results in either insomnia or dysomnia (sleep disorders that causes sleep to lose its restorative capacity). Studies have also shown that GHRH inhibits the actions of somatostatin. Somatostatin is a polypeptide hormone that inhibits GH secretion from the adenohypophysis. Both GHRH and somatostatin are produced in the same neuron but they are released in alternation to each other thereby resulting in the pulsatile release of GH from the neuron.

Recent research has also shown that GHRH is also produced outside the hypothalamus by pancreatic cells, GIT (gastrointestinal tract) epithelial cells and in some neoplastic cells. Clinical studies have also shown that the actions of sermorelin are similar to the GHRH actions. Thus, sermorelin has been used to diagnose deficiencies in GH secretions. Also, sermorelin has been investigated for its therapeutic properties as the studies discussed below show.

Selected Studies.

The two studies reviewed hereafter have provided adequate and conclusive findings that sermorelin can be used clinically to promote growth and manage GHRH deficiency.

1.      Sermolelin and growth hormone (GH) deficiency.

In 1999, a study entitled “Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency” was authored by Aitabh Prakash and Karen Goa and published in the journal Biodrugs. The aim of this study was to investigate whether sermorelin injection stimulates GH secretion from the adenohypophysis. The subjects of this study included adults and pre-pubertal children (both normal and those suffering from GH deficiency). The subjects were randomly divided into two groups with one group receiving intravenous sermorelin injection and the other group receiving subcutaneous sermorelin injection.

The results obtained from both groups showed that intravenous sermorelin injection was able to rapidly diagnose GH insufficiency in children affected by GH deficiency (p < 0.05). The p<0.05 is a measure of statistical significance, and the value 0.05 shows that the results are statistically significant. However, the diagnosis could only isolate GH insufficiency caused by GHRH deficiency. The results also revealed that subcutaneous sermorelin injection did cause a significant increase in height in children suffering from idiopathic GH deficiency, and that this acceleration in growth rate could be maintained consistently for 36 months. Likewise, the results also revealed that both the intravenous and subcutaneous sermorelin administrations were well tolerated with the only observable adverse effects being injection-site pain and transient facial flushing.

In summary, the findings of this study show that sermorelin injection stimulates GH secretion from the adenohypophysis. Also, intravenous sermorelin can be used to diagnose some cases of GH deficiency, and subcutaneous sermorelin can be used to manage GH insufficiency.

2.      Sermolelin and growth acceleration in a chronic disease state.

In 1996, Pasqualini et al conducted a study that was published under the title “Growth acceleration in children with chronic renal failure treated with growth-hormone-releasing hormone (GHRH)” in the journal Medicina. The subjects involved in this study were 9 children aged between 1 to 14 years old. They all suffered from chronic renal failure (CRF). The aim of this study was to investigate whether subcutaneous Sermorelin causes growth increase in children ailing from CRF. The subjects were categorized into 3 groups, the first group comprised of 3 children on conservative management, the second group comprised of 3 children on dialysis and the last group comprised 3 children who had undergone renal transplantation. Each of the three groups was administered with subcutaneous sermorelin acetate (Geref ®) injection for a period of 3-6 months.

The results showed that the mean serum creatinine and urea levels remained stable in all the subjects except for two children on conservative management who showed an increase in their serum creatinine levels. The results also revealed that the rate of height increase in 5 of the subjects (3 on conservative management, one on dialysis and the other had undergone transplantation) averaged about 4.2cm/year (p < 0.05). Also, Geref® caused a higher peak in GH response among growth non-responders as compared to the growth responders (p < 0.05). The results obtained in this study do show that non-responders suffered from GH-resistance as demonstrated by the fact that they had high levels of GH but their growth was still stunted. 

In summary, the findings of this study show that sermorelin does increase the rate of growth in GH-responsive CRF children, though it has no appreciable effect on the course of the CRF.

In conclusion, the above two studies show that Sermorelin can be used to diagnose cases of GH deficiency, stimulates GH secretion from the adenohypophysis, manage GH insufficiency and increase the rate of growth in GH-responsive CRF children.