Economic Reform and Integration Proceedings of the Second International Varna Seminar "On the Way to Convertibility in Central and Eastern European Countries", September 30 - October 3, 1990

These papers were presented at the Second International Varna Seminar organized within the activities of the Economic Reform and Integration (ERI) Project. Fifty-three participants from West and East exchanged experiences and identified prospects for a further integration of this part of Europe into the world economy. It was concluded that national efforts and international support in introducing early convertibility would have to proceed hand in hand

Economic Reform and Integration. Proceedings of 1-3 March 1990 Meeting

The general aim of the IIASA Project on "Economic Reform and Integration" (ERI) can be formulated as establishing bridges between eastern and western economic theory and practice, creating conditions for mutually assimilating successful managerial experience, and for possible rapprochement of economic systems. This volume contains major contributions by Soviet scientists, together with comments by western experts offered during the 1-3 March 1990 ERI Meeting. We believe that this material is of wide and timely interest and may also serve as a reference document for later studies once the time has come to penetrate scientifically the very fast changes we are witnessing today in central and eastern Europe

Executive Guide for East-West Joint Ventures

This Executive Guide is designed to provide useful answers to business executive's basic and most essential questions on East-West joint ventures. The Guide is a result of work by the international network of the Management of Technological Change (MTC) Project at the International Institute for Applied Systems Analysis (IIASA). The answers elucidate legislative practices based on the most recent documentation, as well as administrative practices should they differ. Provisions for each country were examined and approved by the respective chamber of commerce or competent national agency

Economic Reform & Integration Project (ERI) of the Technology, Economy & Society (TES) Program

In summer 1989 IIASA was approached by Academician S. Shatalin of the Soviet Union with the request to consider establishing an activity that could analyze international economic interdependencies and serve as a scientific forum to support economic reforms in the Soviet Union and the other socialist Member countries of our Institute. In late 1989, the Economic Reform and Integration (ERI) Project was established with the general aim of establishing bridges between eastern and western economic theory and practice, creating conditions for mutually assimilating successful managerial experience, and for possible rapprochement of economic systems. This paper presents the current status of the IIASA ERI Project

Administration of Tramadol or Buprenorphine via the drinking water for post-operative analgesia in a mouse-osteotomy model

Adequate analgesia is essential whenever pain might occur in animal experiments. Unfortunately, the selection of suitable analgesics for mice in bone-linked models is limited. Here, we evaluated two analgesics - Tramadol [0.1 mg/ml (Tlow) vs. 1 mg/ml (Thigh)] and Buprenorphine (Bup; 0.009 mg/ml) - after a pre-surgical injection of Buprenorphine, in a mouse-osteotomy model. The aim of this study was to verify the efficacy of these opioids in alleviating pain-related behaviors, to provide evidence for adequate dosages and to examine potential side effects. High concentrations of Tramadol affected water intake, drinking frequency, food intake and body weight negatively in the first 2-3 days post-osteotomy, while home cage activity was comparable between all groups. General wellbeing parameters were strongly influenced by anesthesia and analgesics. Model-specific pain parameters did not indicate more effective pain relief at high concentrations of Tramadol. In addition, ex vivo high-resolution micro computed tomography (µCT) analysis and histology analyzing bone healing outcomes showed no differences between analgesic groups with respect to newly formed mineralized bone, cartilage and vessels. Our results show that high concentrations of Tramadol do not improve pain relief compared to low dosage Tramadol and Buprenorphine, but rather negatively affect animal wellbeing

Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners

Regulatory T cells (Tregs) offer new immunotherapeutic options to control undesired immune reactions, such as those in transplant rejection and autoimmunity. In addition, tissue repair and regeneration depend on a multitude of tightly regulated immune and non-immune cells and signaling molecules. There is mounting evidence that adequate innate responses, and even more importantly balanced adaptive immune responses, are key players in the tissue repair and regeneration processes, even in absence of any immune- related disease or infection. Thus, the anti-inflammatory and anti-apoptotic capacities of Treg can affect not only the effector immune response, creating the appropriate immune environment for successful tissue repair and regeneration, but growing evidence shows that they also have direct effects on tissue cell functions. Here we summarize the present views on how Treg might support tissue regeneration by direct control of undesired immune reactivity and also by direct interaction with non-immune tissue cells. We describe tissue-resident Treg and their specific phenotypes in skin, visceral adipose tissue, and skeletal muscle. In addition, we touch on the topic of osteoimmunology, discussing the direct interactions of Treg with bone-forming cells, such as osteoblasts and their mesenchymal stromal cell (MSC) progenitors—a field which is under-investigated. We hypothesize a cross-talk between Treg and bone-forming cells through the CD39–CD73-(adenosine)-adenosine receptor pathway, which might also potentiate the differentiation of MSCs, thus facilitating bone regeneration. This hypothesis may provide a road map for further investigations on the cross-talk between the immune and the skeletal system, and also enable the development of better strategies to promote bone repair and regeneration

Early pH Changes in Musculoskeletal Tissues upon Injury-Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release

Uncovering the unique characteristics of the mandible to improve clinical approaches to mandibular regeneration

The mandible (lower jaw) bone is aesthetically responsible for shaping the lower face, physiologically in charge of the masticatory movements, and phonetically accountable for the articulation of different phonemes. Thus, pathologies that result in great damage to the mandible severely impact the lives of patients. Mandibular reconstruction techniques are mainly based on the use of flaps, most notably free vascularized fibula flaps. However, the mandible is a craniofacial bone with unique characteristics. Its morphogenesis, morphology, physiology, biomechanics, genetic profile, and osteoimmune environment are different from any other non-craniofacial bone. This fact is especially important to consider during mandibular reconstruction, as all these differences result in unique clinical traits of the mandible that can impact the results of jaw reconstructions. Furthermore, overall changes in the mandible and the flap post-reconstruction may be dissimilar, and the replacement process of the bone graft tissue during healing can take years, which in some cases can result in postsurgical complications. Therefore, the present review highlights the uniqueness of the jaw and how this factor can influence the outcome of its reconstruction while using an exemplary clinical case of pseudoarthrosis in a free vascularized fibula flap

The Role of Immune Reactivity in Bone Regeneration

Bone is a complex organ with the capacity to regenerate. Even with this healing potential, healing results in fractured bone are unsatisfactory in a considerable patient cohort even with a good treatment regimen. These delayed healing cases encourage further research into possible new treatment approaches. The recently developed field of osteoimmunology addressing the tight interconnectivity of the skeletal system and the immune system could be a promising opportunity in this regard. In this review, the complexity of bone and the bone healing process are highlighted with an emphasis on the early healing phase. Specific immune cell subsets are considered for their potential to enhance bone healing and thus to develop new treatment strategies for patients in need

Spatial Distribution of Macrophages During Callus Formation and Maturation Reveals Close Crosstalk Between Macrophages and Newly Forming Vessels

Macrophages are essential players in the process of fracture healing, acting by remodeling of the extracellular matrix and enabling vascularization. Whilst activated macrophages of M1-like phenotype are present in the initial pro-inflammatory phase of hours to days of fracture healing, an anti-inflammatory M2-like macrophage phenotype is supposed to be crucial for the induction of downstream cascades of healing, especially the initiation of vascularization. In a mouse-osteotomy model, we provide a comprehensive characterization of vessel (CD31+, Emcn+) and macrophage phenotypes (F4/80, CD206, CD80, Mac-2) during the process of fracture healing. To this end, we phenotype the phases of vascular regeneration-the expansion phase (d1-d7 after injury) and the remodeling phase of the endothelial network, until tissue integrity is restored (d14-d21 after injury). Vessels which appear during the bone formation process resemble type H endothelium (CD31hiEmcnhi), and are closely connected to osteoprogenitors (Runx2+, Osx+) and F4/80+ macrophages. M1-like macrophages are present in the initial phase of vascularization until day 3 post osteotomy, but they are rare during later regeneration phases. M2-like macrophages localize mainly extramedullary, and CD206+ macrophages are found to express Mac-2+ during the expansion phase. VEGFA expression is initiated by CD80+ cells, including F4/80+ macrophages, until day 3, while subsequently osteoblasts and chondrocytes are main contributors to VEGFA production at the fracture site. Using Longitudinal Intravital Microendoscopy of the Bone (LIMB) we observe changes in the motility and organization of CX3CR1+ cells, which infiltrate the injury site after an osteotomy. A transient accumulation, resulting in spatial polarization of both, endothelial cells and macrophages, in regions distal to the fracture site, is evident. Immunofluorescence histology followed by histocytometric analysis reveals that F4/80+CX3CR1+ myeloid cells precede vascularization