The role of IFN-gamma and IL-4 in gastric mucosa inflammation associated with Helicobacter heilmannii type 1 infection

Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-gamma and IL-4, in H. heilmannii gastric infection in genetically IFN-gamma- or IL-4-deficient mice. The serum IFN-gamma and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmannii-negative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-gamma-/- C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4-/- than in WT BALB/c mice. Serum IFN-gamma levels were significantly higher in IL-4-/- than in WT BALB/c mice, independently of H. heilmannii-positive or -negative status. Although no difference in serum IFN-gamma levels was seen between H. heilmannii-positive (11.3 ± 3.07 pg/mL, mean ± SD) and -negative (11.07 ± 3.5 pg/mL) WT BALB/c mice, in the group of IL-4-/- animals, the serum concentration of IFN-g was significantly higher in the infected ones (38.16 ± 10.5 pg/mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-gamma playing a central role in gastric inflammation.

Collective Memory Embodied in Poetry as Poison. The Mnemonic Role of Romantic Poets Discussed on the Basis of Adam Mickiewicz’ Konrad Wallenrod and Forefathers (Part III)

This thesis constitutes an interdisciplinary approach to the Polish Romanticism combining literature studies with memory studies, nationalism research and psychoanalysis. This phenomenon-based study attempts to answer the question, how the Polish national poet Adam Mickiewicz (1798–1855) – or more exactly the implied authors in his works – perceived the role of poetry in mnemonic terms and how it changes in course of time. Consequently, ‘memory in literature’ (Astrin Erll and Ansger Nünning) is discussed here. Two pieces of writing by Mickiewicz – Konrad Wallenrod [1828] and the third part of Forefathers [1832], where a bard respectively a poetic genius appears – are seen as meta-texts defining goals of poets in time of the political non-existence of a state. Poetry is supposed to keep memory of the glorious past alive, kindle the love for the motherland, support the collective identity of a group and initiate a liberation movement. Poets function as memory guards, leaders of the nation and prophets. Thus, literature is a medium of collective memory – it stores crucial contents, transmits them and acts as a cue. Nevertheless, shifting the focus from the community towards well-being of individuals, which is consistent with the postmodern thinking, the impact that poetry has on members of a given memory culture (Jan Assmann) can be described in ‘vampiric’ terms (Maria Janion). Poetry embodying collective memory may be compared to ‘poison’, ‘infecting’ people with a nationalistic way of thinking to their disadvantage as far as their personal lives are concerned.

Anabolic steroid- and exercise-induced cardiac stress protein (HSP72) in the rat

The present study investigated the effects of exercise and anabolic-androgenic steroids on cardiac HSP72 expression. Male Wistar rats were divided into experimental groups: nandrolone exercise (NE, N = 6), control exercise (CE, N = 6), nandrolone sedentary (NS, N = 6), and control sedentary (CS, N = 6). Animals in the NE and NS groups received a weekly intramuscular injection (6.5 mg/kg of body weight) of nandrolone decanoate, while those in the CS and CE groups received mineral oil as vehicle. Animals in the NE and CE groups were submitted to a progressive running program on a treadmill, for 8 weeks. Fragments of the left ventricle were collected at sacrifice and the relative immunoblot contents of HSP72 were determined. Heart weight to body weight ratio was higher in exercised than in sedentary animals (P < 0.05, 4.65 ± 0.38 vs 4.20 ± 0.47 mg/g, respectively), independently of nandrolone, and in nandrolone-treated than untreated animals (P < 0.05, 4.68 ± 0.47 vs 4.18 ± 0.32 mg/g, respectively), independently of exercise. Cardiac HSP72 accumulation was higher in exercised than in sedentary animals (P < 0.05, 677.16 ± 129.14 vs 246.24 ± 46.30 relative unit, respectively), independently of nandrolone, but not different between nandrolone-treated and untreated animals (P > 0.05, 560.88 ± 127.53 vs 362.52 ± 95.97 relative unit, respectively) independently of exercise. Exercise-induced HSP72 expression was not affected by nandrolone. These levels of HSP72 expression in response to nandrolone administration suggest either a low intracellular stress or a possible less protection to the myocardium.

HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations

Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.

Chlorpheniramine impairs functional recovery in Carassius auratus after telencephalic ablation

We determined the effect of an H1 receptor antagonist on the functional recovery of Carassius auratus submitted to telencephalic ablation. Five days after surgery the fish underwent a spatial-choice learning paradigm test. The fish, weighing 6-12 g, were divided into four groups: telencephalic ablation (A) or sham lesion (S) and saline (SAL) or chlorpheniramine (CPA, ip, 16 mg/kg). For eight consecutive days each animal was trained individually in sessions separated by 24 h (alternate days). Training trials (T1-T8) consisted of finding the food in one of the feeders, which were randomly blocked for each subject. Animals received an intraperitoneal injection of SAL or CPA 10 min after the training trials. The time spent by the animals in each group to find the food (latency) was analyzed separately at T1 and T8 by the Kruskal-Wallis test, followed by the Student Newman-Keuls test. At T1 the latencies (mean ± SEM) of the A-SAL (586.3 ± 13.6) and A-CPA (600 ± 0) groups were significantly longer than those of the S-SAL (226.14 ± 61.15) and S-CPA (356.33 ± 68.8) groups. At T8, the latencies of the A-CPA group (510.11 ± 62.2) remained higher than those of the other groups, all of which showed significantly shorter latencies (A-SAL = 301.91 ± 78.32; S-CPA = 191.58 ± 73.03; S-SAL = 90.28 ± 41) compared with T1. These results support evidence that training can lead to functional recovery of spatial-choice learning in telencephalonless fish and also that the antagonist of the H1 receptor impairs it.

Effects of different general anesthetics on serum hemolysis and hepatic and muscular glycogenolysis in rats

Anesthetics can affect the structure and biological function of tissues and systems differentially. The aim of the present study was to compare three injectable anesthetics generally used in experiments with animals in terms of the degree of hemolysis and glycogenolysis occurring after profound anesthesia. Twenty-four male Wistar rats (330-440 g) were divided into three groups (N = 8): chloral hydrate (CH), ketamine + xylazine (KX), Zoletil 50® (zolazepam and tiletamine) + xylazine (ZTX). After deep anesthesia, total blood was collected. The liver and white (WG) and red gastrocnemius (RG) muscles were also immediately removed. The degree of serum hemolysis was quantified on the basis of hemoglobin concentration (g/L). Hepatic and muscular glycogen concentrations (mmol/kg wet tissue) were quantified by the phenol-sulfuric method. The CH and KX groups exhibited serum hemolysis (4.0 ± 2.2 and 1.9 ± 0.9 g/L, respectively; P < 0.05) compared to the ZTX group, which presented none. Only KX induced elevated glycogenolysis (mmol/kg wet tissue) in the liver (86.9 ± 63.2) and in WG (18.7 ± 9.0) and RG (15.2 ± 7.2; P < 0.05). The CH and ZTX groups exhibited no glycogenolysis in the liver (164.4 ± 41.1 and 176.8 ± 54.4, respectively), WG (28.8 ± 4.4, 32.0 ± 6.5, respectively) or RG (29.0 ± 4.9; 25.3 ± 8.6, respectively). Our data indicate that ZTX seems to be an appropriate general anesthetic for studies that seek to simultaneously quantify the concentration of glycogen and serum biochemical markers without interferences. ZTX is reasonably priced, found easily at veterinary markets, quickly induces deep anesthesia, and presents a low mortality rate.

Purine nucleotides reduce superoxide production by nitric oxide synthase in a murine sepsis model

Sepsis involves a systemic inflammatory response of multiple endogenous mediators, resulting in many of the injurious and sometimes fatal physiological symptoms of the disease. This systemic activation leads to a compromised vascular response and endothelial dysfunction. Purine nucleotides interact with purinoceptors and initiate a variety of physiological processes that play an important role in maintaining cardiovascular function. The purpose of the present study was to investigate the effects of ATP on vascular function in a lipopolysaccharide (LPS) model of sepsis. LPS induced a significant increase in aortic superoxide production 16 h after injection. Addition of ATP to the organ bath incubation solution reduced superoxide production by the aortas of endotoxemic animals. Reactive Blue, an antagonist of the P2Y receptor, blocked the effect of ATP on superoxide production, and the nonselective P2Y agonist MeSATP inhibited superoxide production. Nitric oxide synthase (NOS) inhibition by L-NAME blocked vascular relaxation and reduced superoxide production in LPS-treated animals. In the presence of L-NAME there was no ATP effect on superoxide production. A vascular reactivity study showed that ATP increased maximal relaxation in LPS-treated animals compared to controls. The presence of ATP induced increases in Akt and endothelial NOS phosphorylated proteins in the aorta of septic animals. ATP reduces superoxide release resulting in an improved vasorelaxant response. Sepsis may uncouple NOS to produce superoxide. We showed that ATP through Akt pathway phosphorylated endothelial NOS and “re-couples” NOS function.

Overexpression of kermit/dGIPC is associated with lethality in Drosophila melanogaster

Insertional mutagenesis is an important tool for functional genomics in Drosophila melanogaster. The insertion site in the KG00562 mutant fly line has been mapped to the CG8709 (herein named DmLpin) locus and to the 3’ of kermit (also called dGIPC). This mutant line presents a high lethality rate resulting from a gain of function. To obtain some insight into the biological role of the mutated locus, we have characterized the mutation and its relation to the high mortality of the KG00562 fly line. In this mutant, we did not detect one of the DmLpin transcripts, namely DmLpinK, but we did detect an unusual 2.3-kb mRNA (LpinK-w). Further investigation revealed that the LpinK-w transcript results from an aberrant splicing between the untranslated first exon of DmLpinK and the mini-white marker gene. Lack of DmLpinK or LpinK-w expression does not contribute to lethality, since heterozygous KG00562/Def7860 animals presented lethality rates comparable to those of the wild type. In contrast, the overexpression of kermit was associated with lethality of the KG00562 fly line. Significantly higher levels of kermit were detected in the Malpighian tubules of KG00562/+ flies that presented higher lethality rates than wild-type or KG00562/Def7860 animals, in which the lethality was rescued. In agreement with a recently reported study, our data support the hypothesis that misexpression of kermit/dGIPC could interfere with Drosophila development, with further investigations being needed in this direction.

The acute effects of strength, endurance and concurrent exercises on the Akt/mTOR/p70S6K1 and AMPK signaling pathway responses in rat skeletal muscle

The activation of competing intracellular pathways has been proposed to explain the reduced training adaptations after concurrent strength and endurance exercises (CE). The present study investigated the acute effects of CE, strength exercises (SE), and endurance exercises (EE) on phosphorylated/total ratios of selected AMPK and Akt/mTOR/p70S6K1 pathway proteins in rats. Six animals per exercise group were killed immediately (0 h) and 2 h after each exercise mode. In addition, 6 animals in a non-exercised condition (NE) were killed on the same day and under the same conditions. The levels of AMPK, phospho-Thr172AMPK (p-AMPK), Akt, phospho-Ser473Akt (p-Akt), p70S6K1, phospho-Thr389-p70S6K1(p-p70S6K1), mTOR, phospho-Ser2448mTOR (p-mTOR), and phospho-Thr1462-TSC2 (p-TSC2) expression were evaluated by immunoblotting in total plantaris muscle extracts. The only significant difference detected was an increase (i.e., 87%) in Akt phosphorylated/total ratio in the CE group 2 h after exercise compared to the NE group (P = 0.002). There were no changes in AMPK, TSC2, mTOR, or p70S6K1 ratios when the exercise modes were compared to the NE condition (P ≥ 0.05). In conclusion, our data suggest that low-intensity and low-volume CE might not blunt the training-induced adaptations, since it did not activate competing intracellular pathways in an acute bout of strength and endurance exercises in rat skeletal muscle.

Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in rabbits. No-reflow was not dependent on the reduction of infarct size.

Single-nucleotide polymorphism analysis of GH, GHR, and IGF-1 genes in minipigs

Tibetan (TB) and Bama (BM) miniature pigs are two popular pig breeds that are used as experimental animals in China due to their small body size. Here, we analyzed single-nucleotide polymorphisms (SNPs) in gene fragments that are closely related to growth traits [growth hormone (GH), growth hormone receptor (GHR), and insulin-like growth factor (IGF)-1)] in these pig breeds and a large white (LW) control pig breed. On the basis of the analysis of 100 BMs, 108 TBs, and 50 LWs, the polymorphic distribution levels of GH, GHR, and IGF-1 were significantly different among these three pig breeds. According to correlation analyses between SNPs and five growth traits - body weight (BW), body length (BL), withers height (WH), chest circumference (CC), and abdomen circumference (AC) - three SNP loci in BMs and four SNP loci in TBs significantly affected growth traits. Three SNP sites in BMs and four SNP sites in TBs significantly affected growth traits. SNPs located in the GH gene fragment significantly affected BL and CC at locus 12 and BL at locus 45 in BMs, and also BW, WH, CC, and AC at locus 45 and WH and CC at locus 93 in TBs. One SNP at locus 85 in the BM GHR gene fragment significantly affected all growth traits. All indices were significantly reduced with a mixture of alleles at locus 85. These results provide more information regarding the genetic background of these minipig species and indicate useful selection markers for pig breeding programs.

Conflicting Memory in Estonia: How Do Estonian Russian-speakers Understand the Events of 1939-40?

This thesis studies the collective memory of the Russian-speaking minority living in Estonia. The minority is exposed to two national narratives regarding the incorporation of Estonia into the Soviet Union in 1940. According to the Estonian narrative, Estonia was occupied and annexed by the Soviet Union while the Soviet-Russian narrative sees the actions to have been legal and voluntary. This thesis firstly examines thoughts the existence of these two opposing narratives evoke among the Russian-speaking minority and secondly it explores whether the views of the minority compare with the two official yet divergent narratives. The study focuses on the second and third generation minority members. The topic belongs to the field of memory studies. The objective is to understand the views the Russian minority have towards the controversial events of the years 1939-40. To accomplish the objectives set, a web-based survey using open-ended and multiple-choice questions was conducted. The open-ended questions addressed the main research questions while the multiple-choice questions contributed to forming a more comprehensive understanding of the subject in question. In order to interpret the data, qualitative content analysis has been applied. Based on the findings, the Russian-speaking minority respondents’ understanding of the events of 1939-40 could be described as fragmented, inconsistent and including viewpoints that resulted from the merger of different storylines. There is no single cohesive or coherent narrative of the past amongst the minority. In addition to that, their views do not generally comply with the narrative of the Russian Federation as often referred to in literature, even though the minority respondents do not want to see the Soviet involvement as critically as the Estonian narrative does. Many respondents conceive the events of 1939-40 as ambiguous revealing the ability to be tolerant and receptive in their views regarding the past.

Animal Experience in Kant’s Philosophy

The role of animals in the philosophy of mind is primarily to help understand the human mind by serving as practical examples of cognition that differs from ours either in kind or in degree. Kant regarded animals as beings that only have the faculty of sensibility. By examining what Kant writes about animal experience we gain knowledge concerning the role of sensibility in experience, free from the influence of understanding and reason. I look at Kant’s view of animals in the historical context of alternative views presented by Descartes’ and Hume’s views. Kant’s view can be seen as a counterargument against Descartes’ doctrine of animal machines according to which animals do not have minds and they do not think. I suggest that while it can be argued that some kind of elementary experience could be possible in the physiological level, this only makes sense when it is possible to become conscious of the unconscious sensation, and this requires a mind. A further option is to claim that there is only a difference in degree between human and animal cognitive capacities. This is Hume’s view. I argue that even though Kant’s and Hume’s view on the cognitive capacities of animals seems to depart from each other to a considerable extent, the differences between them diminish when the focus is on the experience these capacities enable. I also briefly discuss the relation of the metaphysics of animal minds to animal ethics.

Globalization of pharmaceutical R&D. Pharmaceutical R&D governance forms in People's Republic of China

Yrityksen selviytyminen ja menestyminen ovat riippuvaisia sen kyvystä innovoida, luoda tietoa ja hyödyntää tietämystä ja keksintöjä (Dunk ja Kilgore 2001). Yrityksen menestyminen erityisesti korkean teknologian alalla on siten suoraan riippuvainen sen T&T:stä, johon tehdyt investoinnit tuovat merkittäviä taloudellisia etuja yritykselle uusien tuotteiden, palveluiden ja prosessien muodossa (McEvily ja Chakravarthy 1999). Teknologinen etumatka ja sen tuotteistaminen innovatiivisiksi tarjoamiksi mahdollistaa monopolististen etujen saavuttamisen yrityksen kansainvälisessä kilpailussa (Lall 1977). Tämä kaltainen kilpailuetu voidaan saavuttaa yrityksen kyvyllä yhdistää maantieteellisesti hajautettu T&T:nsä tehokkaaksi verkostoksi (Porter 1986). Boehen (2008) mukaan T&T:n globalisoitumista voidaan johtaa eri hallintömuodoilla: T&T:n kansainvälistymisellä, T&T:n ulkomaille sijoittamisella ja T&T ulkomaille ulkoistamisella. T&T:n globalisoituminen on osa 2000-luvun taloudellista muutosta, ja sille on esitetty useita vaikuttavia tekijöitä, kuten kustannuserot, työvoimaresurssit, erityisosaamiskeskukset, paikallinen teknologia osaaminen ja kohdemarkkinoiden potentiaali (bardhan 2006; Norwood, ym. 2006; von Zedtwitz ja Gassmann 2002). Tutkimuksen on osoitettu eroavan tuotekehityksestä ja eri tekijöiden on osoitettu vaikuttavan niihin (von Zedtwitz ja Gassmann 2002; Leifer ja Triscari 1987). Samoin T&T on osoitettu olevan jatkumo perustavanlaatuisesta soveltavaan ja lääkekehityksen muodostavan vastaavan T&T jatkumon (Lall 1980; Iansiti 1993), jonka yksittäiset osat vaikuttavat sen hallintomuotoon. Tutkimus esittää eri tekijöitä voivan hyödyntää hallintomuodosta riippuen. Tätä tutkimusta varten tutkija haastatteli lääketeollisuuden johtajia Kiinassa vahvistaakseen tai hylätäkseen eri tekijöitä ja niiden suhdetta lääketeollisen T&T:n hallintomuotoihin. Markkinoiden todettiin olevan ensisijainen tekijä mutta myös kustannuserojen, insentiivien, työvoimaresurssien ja erityisosaamiskeskusten merkitys T&T:n globalisoitumiseen vaikuttavina tekijöinä vahvistettiin yhdessä perusvaatimusten ja riskitekijöiden kanssa. Tutkimuksessa vahvistetaan myös lääketeollisen T&T-jatkumon vaikutus ja esitetään viitekehys hallintomuodoille.

Globalization of pharmaceutical R&D Pharmaceutical R&D governance forms in People's Republic of China

Firm's survival and success, which are dependent on its ability to innovate, to create knowledge and to capitalize on inventions and know-how, is in essence directly linked to its R&D process (Dunk and Kilgore 2001). Especially in technology driven industries, such as the pharmaceuticals, there are significant positive returns to R&D investments through introduction of new or improved products and services (McEvily and Chakravarthy 1999). Technological lead and its transformation to innovative products as fruits of corporate R&D can be seen as monopolistic advantage that helps enterprises to compete in today’s market (Lall 1977). This competitive advantage can be derived from corporation's ability to integrate its activities across geographic locations (Porter 1986). According to Boehe (2008) globalization of R&D can executed with different governance forms: R&D internationalization, R&D offshoring or R&D offshore outsourcing. Globalization of R&D is intervened with the changes in global economy of the 21st century. Some studies argue for its influencing factors to be access to vast skilled labor pools and centers of excellence (Bardhan 2006). Other studies indicate the R&D cost differentials between countries to be the major expected benefit (Norwood et al. 2006). Von Zedtwitz and Gassmann (2002) presented benefits as divided to accessing markets and customers or to accessing local science and technology. This study proposes that based on governance form distinct factor derived benefits can be capitalized. To corroborate or refute factors and their relations on R&D globalization governance forms, an empirical study based on expert interviews of pharmaceutical directors was conducted in the People's Republic of China. The market was found to be the major influencing factor. Local requirements and adaptation were corroborated as factors connected with markets. Furthermore, influencing factors, such as labour, centers of excellence, cost, financial incentives were corroborated together with conditional and risk factors. Furthermore this research argues that the globalization of pharmaceutical R&D is dependent on the financial, scientific and operational requirements of the drug discovery stage. And thus establishes the influence of drug discovery's stages continuum on pharmaceutical R&D globalization. Finally, a R&D globalization governance form decision framework is proposed based on the frameworks presented in literature and author's corroborated empirical findings.