KUMMOONA R Professor of maxillofacial surgery, Chairman Council of maxillofacial surgery, IRAQI BOARD FOR MEDICAL SPCIALIZATIONS, BAGHDAD, IRAQ
Background: In a society struggling to rebuild the country after three decades of years of dictatorships and wars, Iraqi craniofacial and maxillofacial surgeons play a critical role in treatment of many most serious missile injuries of orofacial region by on going conflict in Iraq. This study reflect the modern and advanced surgical techniques of treating explosive missile injuries and other combat and terrorism related injuries and also evaluate the immediate phase and secondary phase managements of 167 patients suffering from missile injuries .
Methods: This studies include one hundred sixty seven patients with missile injuries of orofacial region in a period of 4 years, all injured patients were treated in maxillofacial unite,10th floor, surgical specialties hospital, medical city ,Baghdad.Thier were 134 men and 33 women, the age ranged from 9 to 70 years (mean 39.5 years)
Result: In addition to27 patients with orbital injuries, their were 134 patients men and 33 women; their age ranged from9 to70 years (mean 39.5 years).
Orofacial deformities classified into following 1-sixsty patients(35.9%) had bone loss 2-fifty patients(29.94%) had soft tissue loss 3- twenty seven patients(16.16%) with orbital injuries 4- thirty patients(17.96%) had other deformities' of scar contracture, fistula and sinus formation.
The bony defect was reconstructed by both bone chips carried by osteomesh tray harvested from the iliac crest and by block of cortico-cancellous bone graft from the iliac crest. Soft tissue reconstruction done by local flaps and regional flaps such as lateral cervical and cervico-facial flaps and orbit reconstructed by bone graft, lypholised Dura and sialastic implant. Scar contracture treated by scar revision and sinus tract excised at the same time of scar revision.
Conclusions: Primary phase required an urgent airway management, controlling an active bleeding by surgical intervention; most entrance and exit wounds as well as retained missile were located in the cheek, chin and mandibular body with few cases of mortality due to complication related to head injuries. Secondary phase managements of deformities' of the face as a complication of missile injuries were classified as bone loss, soft tissue loss, combined bone and soft tissue loss and others(sinus tracts and poor scars).
Serum hepcidin level (HEPC) is a significant predictor of arterial stiffness in maintenance hemodialysis patients (mHD) KURAGANO T(1), SHIMONAKA Y(2), YASUNO H(2), KIDA A(1), ITOH K(1), FURUTA M(1), NANAMI M(1), OTAKI Y(1), HASUIKE Y(1), NONOGUCHI H(1), NAKANISHI H(1),
(1) Department of Internal Medicine Division of nephrology and dialysis. Hyogo College of Medicine. (2) Chugai pharmaceutical CO., LTD.
Background: We have already demonstrated that HEPC were significantly higher in mHD than control. Furthermore, in multiple regression analysis, only ferritin (β=0.514, F=75.78, p<0.0001) was selected as a significant predictor of HEPC. Recently, HEPC has been suspected to be linked to the cause of anemia of inflammation and cardiovascular disease (CVD). It has been well known that pulse wave velocity (PWV) is a predictor of CVD. For the purpose of clarifying the relationships among HEPC, iron metabolism and CVD, we evaluated HEPC, indexes of iron metabolism, risk factors of CVD, and brachial-ankle (ba)-PWV in mHD. Methods: 198 mHD, who were treated with erythropoietin and 33 healthy controls were recruited in this study. Hemoglobin (Hb), β2-microglobulin (MG), calcium (Ca), phosphorus (P), intact-parathyroid hormone (int-PTH), total cholesterol (T-CHO), triglyceride (TG), iron, HEPC, ferritin, total iron binding capacity (TIBC), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and ba-PWV were also measured. HEPC was measured by liquid chromatography tandem mass spectrometry. Result: Serum levels of TNF-α(27.1±0.7 vs 5.3±0.9 pg/mL; p<0.0001) , IL-6 (12.4±1.2 vs 3.6±1.1 pg/mL; p=0.017), and HEPC (44.8±2.9 vs 4.4±3.7 ng/mL; p<0.0001) were significantly higher in mHD than control. ba-PWV was significantly correlated with TNF-α( R=0.25 , p= 0.0072), and HEPC (R= 0.28, p=0.0064), but not with IL-6, duration of HD, Kt/V, Ca, P, int-PTH, β2-MG, T-CHO, or TG. In multiple regression analysis, TNF-α (β=0.28, F=7.021, p<0.0001) and HEPC (β=0.26, F= 5.98, p<0.0001) were selected as significant predictors of ba-PWV in mHD. Conclusion; Both HEPC and TNF-α were significant independent predictors of ba-PWV in mHD. These finding show that iron metabolism and inflammation might affect arterial stiffness, which could link to CVD in mHD.
Presentation of usage of new digital technologies in order to advance scientific research in biochemistry and medicine
KURIC L
Beckground: The modern science mainly treats the biochemical basis of sequencing in bio-macromolecules and processes in biochemistry. One can ask weather the language of biochemistry is the adequate scientific language to explain the phenomenon in that science. Is there maybe some other language, out of biochemistry, that determines how the biochemical processes will function and what the structure and organization of life systems will be? The research results provide some answers to these questions. They reveal to us that the process of sequencing in bio-macromolecules is conditioned and determined not only through biochemical, but also through cybernetic and information principles.
Methods: What we did is the following: We translated the physical and chemical parameters from the language of biochemistry into the digital language of programmatic, cybernetic and information principles. This we did by using the adequate mathematical algorithms. By using chemical-information procedures, we calculated the numerical value for the information content of molecules. What we got this way is the digital picture of the phenomenon of biochemistry. These digital pictures reveal to us a whole new dimension of this science.
Results: Within the digital pictures in biochemistry, the physical and chemical parameters are in a strict compliance with programmatic, cybernetic and information principles. As an example, we will here give you the mathematical gravity forces. These forces determine the positioning of aminoacids in their molecules. Each bar in the protein chain attracts only the corresponding aminoacid, and only the relevant aminoacid can be positioned at certain place in the chain. Each peptide chain can have the exact number of aminoacids necessary to meet the strictly determined mathematical conditioning. It can have as many atoms as necessary to meet the mathematical balance of the biochemical phenomenon at certain mathematical level, etc
Conclusion(s): 1)The process of sequencing in bio-macromolecules is conditioned and determined not only through biochemical, but also through cybernetic and information principles. 2)The digital pictures of biochemistry provide us with cybernetic and information interpretation of the scientific facts. 3)Now we have the exact scientific proofs that there is a genetic language that can be described by the theory of systems, and which functions in accordance with certain principles.
Acridine orange found in Ehrlich’s era could become a “Magic Bullet” against cancer under photon energy KUSUZAKI K1, MURATA H3, MATSUBARA T2, SATONAKA H2, NAKAMURA T2, MATSUMINE A2, UCHIDA A2 1Odai Kosei Hospital, Taki Mie Japan, 2Mie University Faculty of Medicine, Tsu, Mie, Japan, 3Kyoto Prefectural University of Medicine, Kyoto, Japan.
Background: Acridine orange (AO) was extracted as a dye from coal tar over a hundred year ago and used for saining of cells or micro-organisms when Paul Ehrlich actively worked. It has various unique biological activities and has been shown to be a useful fluorescent dye specific for DNA and RNA, a pH indicator, photosensitizer, anti-tumor and anti-malarial drug, and detector of bacteria and parasites. We recently found that AO accumulates in musculoskeletal sarcomas and that after illumination of the tumors with visible light or irradiation with low-dose X-rays, the dye rapidly exerts selective cytocidal effect against the sarcoma cells.
Methods: We have been applying surgery combined with photo- (PDT) or radiodynamic therapy (RDT) with AO (AO-PDT & RDT) to patients with musculoskeletal sarcomas after reduction surgery, to maintain an excellent limb function.
Results: The results of a clinical study on the outcome of this therapeutic strategy revealed that it yielded better local control and remarkably better limb function than wide resectional surgery.
Discussions: Based on our experimental studies, it was clarified that AO accumulates in acidic organelles or structures, especially lysosomes, depending on the acidity. An enormous number of protons are produced in cancer from lactate or CO2 under hypoxic conditions, which are move into the extracellular fluid or lysosomes to maintain the intracellular fluid pH. Therefore, AO shows marked accumulation in the acidic lysosomes of cancer cells. Photon energy from visible light or X-rays excites the AO accumulated in lysosomes; the excited AO emits fluorescence and forms activated oxygen from intracytoplasmic oxygen. The activated oxygen destroys lysosomes, with the released lysosomal enzymes causing rapid death of the cancer cells. On the other hand, normal cells can exclude AO quickly because they are not acidic. Thus, AO-PDT and AO-RDT exhibit strong and selective cytocidal effect against malignant tumors.
Conclusions: We believe that AO-PDT and AO-RDT exhibit selective anti-cancer cell activity and that AO excited by photon energy has excellent potential as an anti-cancer agent like Magic Bullets which Paul Ehrlich suggested.
Extremely High Natriuretic Effect of 1-Desamino-8-homoarginine Vasotocin in Rats KUTINA AV, NATOCHIN JuV
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science, Saint-Petersburg, Russia.
Background: Mammalian kidney retains sodium and therefore maintains extracellular fluid volume. Recently we have shown that vasotocin (VT) induces sharp increase in renal sodium excretion in rats (Gao, Natochin, 2004). It was important to synthesize new analogues of this hormone and to study their effect on renal functions in attempt to create a more effective and selective natriuretic peptide. In this work we studied a new VT analogue - 1-desamino-8-homoarginine vasotocin (1d-hAVT).
Methods: This study included 73 female Wistar rats: 43 rats were given the single intramuscular injection of 0.001 - 1 nmol/kg 1d-hAVT, 15 rats – 3 µmol/kg furosemide and 15 rats served as control. During the experiment the rats were kept in individual cages and urine samples were collected during 3 h. Urinary osmolality and electrolytes (Na, K) were measured by micro-osmometry and flame photometry, respectively. 1d-hAVT was synthesized by MI Titov, II Eliseev. ANOVA and Dunn post-hoc tests were used for statistical analysis.
Results: 1d-hAVT injection (1 or 0.5 nmol/kg) increased diuresis, sodium and potassium excretion (table), its action lasted approximately 2 h. Enhancement of natriuresis coincided with a high solute-free water reabsorption, which indicates preserved antidiuretic action of 1d-hAVT. It had the approximately 1.8-fold greater effect on sodium excretion than VT. 1d-hAVT and the loop diuretic furosemide have comparable natriuretic effect (p>0.05).
Conclusions: 1) The new VT analogue (1d-hAVT) has a high natriuretic effect and stimulates solute-free water reabsorption in the rat kidney. 2) Findings that 1d-hAVT at nanomolar doses induced natriuresis suggest existence of an intracellular cascade of signal enhancement through V-receptors. 3) Effectiveness of 1d-hAVT was 25000 times greater as compared with equimolar doses of furosemide. Using Ehrlich’s term, 1d-hAVT act as the selective natriuretic “Magic Bullet”.
Dynamics Based Design of Anti-Prion Compounds Uncovered the Hot Spots for Prion‘s Pathogenic Conversion Reaction KUWATA K, MATSUMOTO T, KAMATARI YO, MUTO JH, NAKAMURA HK
Center for Emerging Infectious Diseases, Gifu Univ., Gifu City, Japan
Background: Prion proteins are key molecules in transmissible spongiform encephalopathies (TSEs). Although the precise mechanism of the conformational conversion process from the cellular form (PrPC) to the scrapie form (PrPSc) is still unknown, we demonstrated that it is totally feasible to design a chemical chaperon which can stabilize the PrPC conformation, and regulate the converison reaction. In oredr to design the chaperon, we utilized the slow dynamical information of a prion protein, and concomittantly identified the hots spots for pathogenic conversion reaction.
Methods: We conducted in silico screening to find compounds that fitted into a ‘pocket’ created by residues undergoing the conformational rearrangements between the native- and the sparsely populated high energy states (PrP*) elucidated by Carr-Purcell Meiboom-Gill relaxation dispersion method (NMR), and directly bind to those residues. Hit compounds were tested by ex vivo and in vivo screening, and if effective, they were subjected to determination of the complex structure and further lead optimization processes. The cyclic process between (1) structure determination, (2) in silico design, (3) organic synthesis, and (4) bioassay, termed Dynamics Based Drug Design (DBDD), was repeated recursively.
Results: More than hundred compounds were tested in a TSE-infected cell culture model, and more than twenty compounds including, 2-pyrrolidin-1-yl-N-[4-[4-(2- pyrrolidin-1-yl-acetylamino)-benzyl]-phenyl]-acetamide, termed GN8, efficiently reduced PrPSc.Subsequently, administration of GN8 was found to prolong the survival of TSE-infected mice. Heteronucler NMR and computer simulation showed that the specific binding sites are the A-S2 loop (N159) and the region from helix B (V189, T192 and K194) to B-C loop (E196), indicating that the intercalation of these distant regions termed ‘Hot Spots’ hampers the pathogenic conversion process.
Conclusions: Dynamics Based Drug Discovery (DBDD) strategy demonstrated here focusing on the hot spot of PrPc will open the way to the development of novel anti-prion drugs.
Polymyxins: Differences & Similarities between Polymyxin B and Polymyxin E (Colistin), and their recent developments KWA AL1, KASIAKOU SK3, TAM VH2, FALAGAS ME 3,4 1. Department of Pharmacy, Singapore General Hospital, Singapore, 2. Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, Texas, USA, 3. Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece, 4. Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.
Hospital-acquired infections due to multidrug-resistant Gram-negative bacteria constitute major health problems, since the medical community is continuously running out of available effective antibiotics and no new agents are in the pipeline. Polymyxins, a group of antibacterials that was discovered during the late 1940s represent last treatment options for these infections. Commercially only two polymyxins are available, polymyxin E (colistin) and polymyxin B. Although several reviews have been recently published about colistin, no review has focused on the similarities and differences between polymyxin B and colistin. These two medications have many similarities with respect to mechanism of action, antimicrobial spectrum, clinical uses, and toxicity. However, they also differ in several points including chemical structure, formulation, potency, dosage, and pharmacokinetic properties. These differences will be described, with elucidation of their most recent developments
Oral Tolerance as a Method of Suppression of Immunological Response in Experimental Autoimmune Encephalomyelitis
1Medical Research Center, Polish Academy of Sciences, Warsaw, Poland, 2Children’s Memorial Health Institute, Warsaw, Poland, 3Industrial Chemistry Research Institute Warsaw, Poland.
Background: Recently has been proposed to apply a method of oral tolerance to ameliorate auto-immune reactions. The aim of this study was to use the hydrolysate of pig spinal cord proteins (mixture of neuroantigens) to induce oral tolerance in the animal model of sclerosis multiplex (SM) - experimental allergic encephalomyelitis (EAE).
Methods: The female Lewis rats were fed with pig spinal cord hydrolysate in two doses for one week before immunization, which was induced by injection of guinea pig spinal cord homogenate. The clinical course was observed and evaluated in a five grade scale. At the peak of clinical symptoms (the 13th day post immunization) the rats were sacrificed and the spleen removed. Splenocytes were suspended in a culture medium and placed in microculture plates. The cells were stimulated with homogenate alone, hydrolysate alone, mixture of homogenate + hydrolysate, and medium alone. The cells were cultured for seven days. Subsequently, proliferation of splenocytes was estimated by means of {3H}thymidine incorporation and expressed in cpm (average of triplicate samples). In supernatants of cultures of splenocytes the level of cytokines interferon gamma (IFN-γ), interleukin (IL)-10, IL-4, and tumor growth factor (TGF)-α was measured.
Results: It was demonstrated that homogenate-induced splenocytes of hydrolysate-fed rats gave rise to low proliferation as compared to the controls used. The IFN-γ was inhibited in hydrolysate-fed animals as well as in hydrolysate-stimulated samples.
Conclusion: The results show that the hydrolysate of pig spinal cord proteins has a modulatory effect on the immune reaction, particularly on the orally-induced antigen-specific modulation of autoimmune response. It might have a clinical implication in SM treatment.
