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TRANSPLANTATION OF BONE MARROW STROMAL CELLS INTO AN INJURED CNS K. Glogarov, P. Jendelov, V. Herynek1, M. Hjek1, E. Sykov Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University and 1Institute for Clinical and Experimental Medicine, Prague, Czech Republic Bone marrow stromal cells MSC ; are pluripotent progenitor cells that have the capability to migrate towards lesions and induce or facilitate sitedependent differentiation in response to environmental signals 1 ; . Using in vivo MR imaging, we studied MSC transplantated into adult rats with a cortical photochemical lesion 2 ; . MSC were isolated from rat bone marrow by adherence to plastic. After in vitro expansion, the cells were co-labeled with superparamagnetic iron-oxide nanoparticles Endorem, Guerbert Laboratories, France ; and BrdU 5 M ; 48 hours prior to transplantation and administered either intracerebrally into the contralateral hemisphere 0.3 million cells in 3 l PBS; n 12 ; or i.v. into the femoral vein 2 million cells in 0.5 ml PBS; n 8 ; . A photochemical lesion was induced by rose bengal light beam interaction 24 hours prior to transplantation. MR images were taken weekly using a 4.7 T Bruker spectrometer. Rats were sacrificed 4 weeks following transplantation, and the fate of transplanted cells in the CNS was analyzed immunohistochemically. The cells preferentially migrated into the lesion, and subsequently some of the cells that entered the lesion expressed the neuronal marker NeuN. In animals without a lesion, the majority of intracerebrally injected cells remained in the close vicinity of the needle track. Starting 7 days after transplantation and persisting for 4 weeks, MR images showed a hypointense signal in the lesion, indicating the migration of cells to the lesion. Hypointensity was also found in the lesion after i.v. injection of labeled cells. Prussian blue staining confirmed the presence of iron-oxide-labeled cells in the lesion site. The study demonstrates that iron-oxide nanoparticles can be used to track implanted stem cells in the CNS.

The Africa OR TA Project II, in collaboration with other consortium members, has developed a methodology for conducting case studies of programs and projects that have developed an integrated approach to providing STI, HIV, AIDS and MCH-FP services. This methodology was used to carry out this case study of the Mkomani Clinic Society. The cost analysis component of the study was carried out under the auspices of the USAID REDSO Networking Program. Review of available data and reports: The KDHS reports, MOH Annual Reports, Census reports, and various reports and strategic plans prepared by the MCS were reviewed. The review was used to establish the characteristics of the catchment area and population, fertility indices, contraceptive practices and statistics of STIs, HIV and AIDS. The review was also used to trace the evolution of the MCS services to the time of the case study and to identify future plans. In-depth interview with Program Director: The MCS Program Director was interviewed using a semi-structured interview guide. The interview guide covered the Director's understanding of the integration process, the historical evolution of the integration process why, how and when did the process start ; , the type of integration model and its components, activities carried out to facilitate the process, resource mobilization and budgeting, monitoring and evaluation activities, policy commitment, experiences to date and future plans. Situation Analysis: Using a modified Situation Analysis approach based on the approach developed and used by the Population Council to study family planning programs in the region ; , data were collected on the status of clinic facilities, management information systems, personnel, client experiences at the clinics, the non clinic-based service delivery systems, and service statistics. With this approach, data are collected using a clinic inventory, interviews with staff, and exit interviews with FP and MCH clients. The modification involved an expansion of the existing data collection instruments to include questions on staff and client knowledge of STIs, HIV and AIDS, staff use of STI management procedures risk assessment, diagnosis, treatment, counseling, IEC and referral ; , and the actual and potential mechanisms for integration of STI HIV AIDS services with MCH-FP services. An inventory was prepared for each of the two MCS clinics using a modified inventory data collection instrument. Information on accessability, publicity, physical infrastructure, supplies, equipment, commodities and service statistics was obtained for each facility. All professional staff who provide MCH-FP services at the two MCS clinics were interviewed. This included five doctors, five nurses, one CSW coordinator and two laboratory technicians. With the exception of the two laboratory technicians, all the other staff were interviewed using the modified staff interview guide. Interviews were held with 14 of the 30 CSWs working with the MCS services. All the 14 CSWs interviewed were providing the basic MCH-FP services that include: motivation and counseling for all MCH-FP services, distribution of non prescription methods of family planning including oral contraceptives, referral for prescription methods and follow up of MCH-FP clients. A total of 36 women who received MCH-FP services at the two clinics were interviewed about their interactions with the MCH-FP clinic staff. The majority, 19, had attended the clinic 8 and proscar, for example, vaginal cream. TEVA Pharmaceuticals USA Teva Pharmaceutical Industries Ltd. GATE Pharmaceuticals. 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It was found that only 12% of those interviewed reported that obesity or physical inactivity were causally related to diabetes.6 The findings of CURES strongly indicated that measures to raise awareness of diabetes and control the condition are still grossly inadequate in India and that largescale diabetes awareness and control programmes are urgently needed. Large-scale awareness and control programmes are urgently needed. Objectives The principal objectives of the PACE programme include the following: the implementation of a massive public diabetes awareness programme aimed at over one million people the realization of large-scale screening for diabetes and impaired glucose tolerance higher than normal blood glucose levels, but below the level of a person with diabetes, and increased risk for developing type 2 diabetes ; in at least 200 000 people the implementation of a community-based diabetes prevention programme to promote therapeutic lifestyle changes. 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10. Kankirawatana P, Raksadawan N. Neuroleptic malignant syndrome. Siriraj Hosp Gaz 1995; 47: 130-33. Keck PE, Jr., Pope HG, Jr., Cohen BM, McElroy SL, Nierenberg AA. Risk factors for neuroleptic malignant syndrome. A casecontrol study. Arch Gen Psychiatry 1989; 46: 914-8. Richard IH. Acute, drug-induced, lifethreatening neurological syndromes. The Neurologist 1998; 4: 196-210. Smego RA, Jr., Durack DT. The neuroleptic malignant syndrome. Arch Intern Med 1982; 142: 1183-5. Trollor JN, Sachdev PS. Electroconvulsive treatment of neuroleptic malignant syndrome: a review and report of cases. Aust N Z J Psychiatry 1999; 33: 650-9.

PHLS and NHS laboratories in England and Wales process clinical specimens for the diagnosis of mycobacterial infections, and send isolates for species identification and drug sensitivity testing to a mycobacterial reference centre PHLS Mycobacterium Reference Unit Dulwich, PHLS Regional Centres for Mycobacteriology Birmingham, Cardiff, and Newcastle, and Royal Brompton Hospital ; . The source laboratories are asked to report, on a voluntary basis, clinically significant mycobacterial infections to the PHLS Communicable Disease Surveillance Centre CDSC ; . Reports are collated by the Tuberculosis Section at CDSC. Information on reported mycobacterial infections has previously been published in the form of summary tables in the CDR Weekly every 8 weeks. Guidelines for reporting were last published in 19951. With the development of an improved laboratory reporting system LabBase2 ; , and the evolution of the CDR Weekly as an electronic journal, a revision of the reporting guidelines is timely. This guidance has been drafted on the basis of advice received from the PHLS Mycobacteriology Forum and ramipril.

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Kaune WT, Feychting M, Ahlbom A, Ulrich RM and Savitz DA 1998 ; . Temporal characteristics of transmission-line loadings in the Swedish Childhood Cancer Study. Bioelectromagnetics, 19, 35465. Kaune WT, Miller MC, Linet MS, Hatch EE, Kleinerman RA, Wacholder S, Mohr AH, Tarone RH and Haines C 2000a ; . Children's exposure to magnetic fields produced by US television sets used for viewing programs and playing video games. Bioelectromagnetics, 21, 21427. Kaune WT, Bracken TD, Senior RS, Rankin RK, Niple JC and Kavet R 2000b ; . Rate of occurrence of transient magnetic field events in US residences. Bioelectromagnetics, 21, 197213. Kaune WT, Davis S, Stevens RG, Mirick DK and Kheifets L 2001 ; . Measuring temporal variability in residential magnetic field exposures. Bioelectromagnetics, 22, 23245. Kaune WT, Miller MC, Linet MS, Hatch EE, Kleinerman RA, Wacholder S, Mohr AH, Tarone RE and Haines C 2002 ; . Magnetic fields produced by hand-held hair dryers, stereo headsets, home sewing machines and electric clocks. Bioelectromagnetics, 23, 1425. Kavet R 1998 ; . ELF magnetic fields, transients and TWA metrics. In Exposure Metrics and Dosimetry for EMF Epidemiology AF McKinlay and MH Repacholi, eds ; . Radiat Prot Dosim, 83, 2940. Kavet R, Silva JM and Thornton D 1992 ; . Magnetic field exposure assessment for adult residents of Main who live near and far away from overhead transmission lines. Bioelectromagnetics, 13, 3555. Kelsh MA, Kheifets L and Smith R 2000 ; . The impact of work environment, utility and sampling design on occupational magnetic field exposure summaries. Ind Hyg Assoc J, 61, 17482. Kelsh MA, Bracken TD, Sahl JD, Shum M and Ebi KL 2003 ; . Occupational magnetic field exposures of garment workers: results of personal and survey measurements. Bioelectromagnetics, 24, 31626. Kheifets LI, London SJ and Peters JM 1997 ; . Leukaemia risk and occupational electric field exposure in Los Angeles County, California. J Epidemiol, 146 1 ; , 8790. Mader DL and Peralta SB 1986 ; . Residential exposure to 60 Hz magnetic fields from appliances. Health Phys, 51 2 ; , 21525. Maslanyj MP 1996 ; . Power-frequency electromagnetic fields associated with local area substations. Chilton, NRPB-M751. Maslanyj MP and Allen SG 1998 ; . A review of electromagnetic fields associated with motorised appliances. London, HSE Contract Research Report 172. Maslanyj MP, Mee TJ and Allen SG 2005 ; . Investigation and identification of sources of residential magnetic field exposures in the United Kingdom Childhood Cancer Study UKCCS ; . Chilton, HPA-RPD-005. Merchant CJ, Renew DC and Swanson J 1994 ; . Exposures to power frequency magnetic fields in the home. J Radiol Prot, 14, 7787. Mezei G, Kheifets LI, Nelson LM, Mills KM, Iriye R and Kelsey JL 2001 ; . Household appliance use and residential exposure to 60 Hz magnetic fields. J Exp Anal Environ Epidemiol, 11, 419. NRC National Research Council ; 1996 ; . Possible health effects of exposure to residential electric and magnetic fields. Washington DC, National Academy Press. NRPB 2004 ; . Review of the scientific evidence for limiting exposure to electromagnetic fields 0300 GHz ; . Doc NRPB, 15 3 ; , 1224. Polk C 1974 ; . Propagation, amplitude and temporal variation of extremely low frequency 0100 Hz ; electromagnetic fields. In Biologic and Clinical Effects of Low-frequency Magnetic and Electric Fields JG Llaurao et al, eds ; . Springfield, Thomas. Preece AW, Grainger P, Golding J and Kaune W 1997 ; . Magnetic fields from domestic appliances in the UK. Phys Med Biol, 42, 6776. Silva M, Hummon N, Rutter D and Hooper C 1989 ; . Power frequency magnetic fields in the home. IEEE Trans Power Deliv, 4, 46577. Swanson J 1996 ; . Net currents in underground distribution circuits in the UK: implications for assessing magnetic field exposures. J Radiol Prot, 16 4 ; , 27586. Swanson J 1999 ; . Residential power-frequency electric and magnetic fields: sources and exposures. Radiat Prot Dosim, 83 12 ; , 914 and rimonabant. Dosing Range 5-10 mg kg q8 200-800 mg 5x day 0.5-1 mg kg q24 250-500 mg q8 250-500 mg q8 1-2 gm q4-6 1.5 to 3 gm q6h 500 mg on day 1 then 250 mg on days 2-5 500 mg q24 1-2 gm q8 1-2 gm q8 1-2 gm q12 200 mg q12 1-2 gm q8 1 gm q24 see footnote ; 750 mg q8 250-500 mg q6 200-400 mg q12 500-750 mg q12 600-900 mg q8 150-450 mg q6 10-20 ml q12 10 ml 1 double strength tablet ; 1 double strength q12 100mg q12-24 200-400 mg q24 5mg kg q12 500 mg q24 750 mg q24 d 1 gm.
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Chemicals [5-3H]uridine 23.6 Ci mmol ; , [8-3H]guanosine 14.7 Ci mmol ; , and [methyl-3H]thymidine 20 Ci mmol ; were purchased from Moravek Biochemicals, Brea, CA ; . Nucleoside analogs valinomycin and phloridzin were obtained from Sigma Chemical St. Louis, MO ; . All other chemicals were of the highest analytical grade available. Procurement of Human Intestines This study was approved by the institutional review board of the University of Washington. Fetal intestines. Human fetal small intestines of various gestational ages 918 wk old ; were collected from normal abortuses of both sexes, immediately snap frozen in liquid nitrogen, and then stored at 70C until use. Five to twentyone fetal intestines of similar gestational age within an age range of 14 days ; were pooled for each transport experiment. Except for longitudinal activity studies, in which fetal intestines from duodenum to cecum ; were divided into two equal segments, proximal and distal, brush-border membrane vesicles BBMV ; were isolated from whole fetal intestines. Adult intestines. Human intestines from the ligament of Treitz to the cecum ; were obtained from breathing adult organ donors victims of vehicular or cerebrovascular accidents in otherwise good health ; of both sexes. After the duodenum the first foot ; was separated, the small intestines were divided into two equal segments, with the proximal half representing the jejunum and the distal half the ileum. The jejunal and ileal segments were subdivided into 1-foot segments, each of which was rinsed with ice-cold saline solution to remove luminal debris. The last 23 feet of the intestine was defined as the distal ileum, and the last foot was defined as the terminal ileum. The tissues were stored at 70C until use. For longitudinal activity studies, BBMV were prepared separately from the duodenum 1st foot ; , proximal jejunum 3rd foot ; , midpoint of the small intestine usually 7th9th foot ; , and distal ileum last 23 feet ; of each subject total of 5 subjects ; on the same day. Preparation of BBMV Fetal and adult intestines were thawed on ice, and BBMV were purified by the Mg2 precipitation method as described previously 17 ; . Membrane potential was clamped using the K ionophore valinomycin 3 M ; . The purity of these preparations was routinely determined by assaying enzyme. AVENZOR FOR PHARMACEUTICAL INDUSTRIES S.A. AVES AVIACOR AVIN OIL ANSTALT AVK INTERNATIONAL A S AVRASYA TECHNOLOGY ENGINEERING & CONS. INC and sildenafil.
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Holscher, C. and Rose, S.P.R. 1994. Inhibitors of phospholipase A2 produce amnesia for a passive avoidance task in the chick. Behav. Neural Biol. 61: 225232. Holscher, C., Canevari, L., and Richter-Levin, G. 1995. Inhibitors of PLA2 and NO synthase cooperate in producing amnesia of a spatial task. Neuroreport 6: 730732. Izquierdo, I., Fin, C., Schmitz, P.K., Da Silva, R., Jerusalinsky, D., Quillfeldt, J.A., Ferreiara, M.B.C., Medina, J.H., and Bazan, N.G. 1995. Memory enhancement by intrahippocampal, intraamygdala, or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance task. Proc. Natl. Acad. Sci. 92: 50475051. Jerusalinsky, D., Fin, C., Quillfeldt, J.A., Ferreiara, M.B.C., Schmitz, P.K., Da Silva, R., Walz, R., Bazan, N.G., Medina, J.H., and Izquierdo, I. 1994. Effect of antagonists of platelet-activating factor receptors on memory of inhibitory avoidance in rats. Behav. Neural Biol. 62: 13. Kaufmann, W.E., Worley, P.F., Pegg, J., Bremer, M., and Isakson, P. 1996. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Proc. Natl. Acad. Sci. 93: 23172321. Kimura, H., Okamoto, K., and Sakai, Y. 1985. Modulatory effects of prostaglandin D2, E2, and F2 on the postsynaptic actions of inhibitory and excitatory amino acids in cerebellar Purkinje cell dendrites in vitro. Brain Res. 330: 235244. Kujubu, D.A., Bradley, S., Fletcher, B.S., Varnum, B.C., Lim, R.W., and Herschman, H.R. 1991. TIS10, a phorbol ester tumor promotor-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase cyclooxygenase homologue. J. Biol. Chem. 266: 1286612872. Laneuville, O., Breuer, D.K., Dewitt, D.L., Hla, T., Funk, C.D., and Smith, W.L. 1994. Differential inhibition of human prostaglandin endoperoxide H synthases-1 and -2 by nonsteroidal anti-inflammatory drugs. J. Pharmacol. Exp. Ther. 271: 927934. Lazarewicz, R. and Salinska, E. 1995. N-methyl-D-aspartate-evoked release of cyclo-oxygenase products in rabbit hippocampus: An in vivo microdialysis study. J. Neuorsci. Res. 40: 660666. Masferrer, J.L., Zweifel, B.S., Manning, P.T., Hauser, S.D., Leahy, K.M., Smith, W.G., Isakson, P.C., and Seibert, K. 1994. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc. Natl. Acad. Sci. 91: 32283232. McDonald, R.J. and White, N.M. 1993. A triple dissociation of memory systems: Hippocampus, amygdala, and dorsal striatum. Behav. Neurosci. 107: 322 1994. Parallel information processing in the water maze: Evidence for independent memory systems involving the dorsal striatum and hippocampus. Behav. Neural Biol. 61: 260270. McGaugh, J.L. 1966. Time-dependent processes in memory storage. Science 153: 13511358 1973. Drug facilitation of learning and memory storage. Science 153: 229240 1989. Dissociating learning and performance: Drug and hormone enhancement of memory storage. Brain Res. Bull. 23: 339345. Mishkin, M. and Petri, H.L. 1984. Memories and habits: Some implications for the analysis of learning and retention. In Neuropsychology of memory L.R. Squire and N. Butters, eds. ; , pp. 287296. Guilford, New York, NY. Mitchell, J.A., Akarasereenot, P., Thiemermann, C., Flower, R.J., and Vane, J.R. 1993. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc. Natl. Acad. Sci. 90: 1169311697. Mondadori, C., Weiskrantz, L., Buerki, H., Petschke, F., and Fagg, G.E. 1989. NMDA receptor antagonists can enhance or impair learning performance in animals. Exp. Brain Res. 75: 449456. Morris, R.G.M., Garrud, P., Rawlins, J.N.P., and O'Keefe, J. 1982. Place navigation impaired in rats with hippocampal lesions. Nature 297: 681683. Morris, R.G.M., Davis, S., and Butcher, S.P. 1990. Hippocampal synaptic plasticity and NMDA receptors: A role in information storage? Philos. Trans. R. Soc. London 329: 187204.
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