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PubMedDate not supplied

Psychosocial factors and immunity in nonhuman primates: a review.

This review summarizes research from several laboratories that has assessed the influence of psychosocial factors on immune responses in nonhuman primates. These studies have demonstrated that the formation and disruption of social relationships should be viewed as significant psychobiological events with many immunologic sequelae, especially for the young monkey. Prolonged changes in leukocyte numbers, in vitro measures of lymphocyte function, and antibody responses to antigenic challenge have been reliably observed. There is also evidence in infant monkeys suggesting that normal maternal care may be important for the development and maintenance of the physiological set points for certain immune responses. Similarly, immune responses in adult monkeys can be affected by the level of aggression occurring within the group. Collectively, this research reiterates the important influence that psychosocial variables can have on basic physiological responses, particularly when social relationships are in the process of change.

Adrenal Cortex↗
PubMed2006

Modification of the trypsin-dependent cleavage activation site of the human metapneumovirus fusion protein to be trypsin independent does not increase replication or spread in rodents or nonhuman primates.

The contribution of cleavage activation of the fusion F protein of human metapneumovirus (HMPV) to replication and pathogenicity in rodents and nonhuman primates was investigated. Recombinant HMPVs were generated in which the naturally occurring trypsin-dependent cleavage sequence (R-Q-S-R downward arrow) was replaced by each of three sequences whose cleavage in vitro does not depend upon added trypsin. Two of these were multibasic sequences derived from avian metapneumovirus type A (R-R-R-R) or type C (R-K-A-R), with the former containing the consensus furin protease cleavage motif (R-X-R/K-R downward arrow). The third one (R-Q-P-R) was derived from a recently described trypsin independent HMPV isolate (J. H. Schickli, J. Kaur, N. Ulbrandt, R. R. Spaete, and R. S. Tang, J. Virol. 79:10678-10689, 2005). To preclude the possibility of conferring even greater virulence to this significant human pathogen, the modifications were done in an HMPV variant that was attenuated by the deletion of two of the three envelope glycoproteins, SH and G. Each of the introduced cleavage sequences conferred trypsin independent F cleavage and growth to HMPV in vitro. However, they differed in the efficiency of trypsin independent growth and plaque formation in vitro: R-R-R-R > R-K-A-R > R-Q-P-R > R-Q-S-R. The R-R-R-R mutant was the only one whose growth in vitro was not augmented by added trypsin, indicative of highly efficient trypsin independent cleavage. When inoculated intranasally into hamsters, there was essentially no difference in the magnitude of replication in the upper or lower respiratory tract between the mutants, and virus was not detected in organs outside of the respiratory tract. Evaluation of the most cleavage-efficient mutant, R-R-R-R, in African green monkeys showed that there was no detectable change in the magnitude of replication in the upper and lower respiratory tract or in immunogenicity and protective efficacy against HMPV challenge. These results suggest that cleavage activation is not a major determinant of HMPV virulence.

Amino Acid Sequence↗
PubMed2004

Frequent simian foamy virus infection in persons occupationally exposed to nonhuman primates.

The recognition that AIDS originated as a zoonosis heightens public health concerns associated with human infection by simian retroviruses endemic in nonhuman primates (NHPs). These retroviruses include simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus (STLV), simian type D retrovirus (SRV), and simian foamy virus (SFV). Although occasional infection with SIV, SRV, or SFV in persons occupationally exposed to NHPs has been reported, the characteristics and significance of these zoonotic infections are not fully defined. Surveillance for simian retroviruses at three research centers and two zoos identified no SIV, SRV, or STLV infection in 187 participants. However, 10 of 187 persons (5.3%) tested positive for SFV antibodies by Western blot (WB) analysis. Eight of the 10 were males, and 3 of the 10 worked at zoos. SFV integrase gene (int) and gag sequences were PCR amplified from the peripheral blood lymphocytes available from 9 of the 10 persons. Phylogenetic analysis showed SFV infection originating from chimpanzees (n = 8) and baboons (n = 1). SFV seropositivity for periods of 8 to 26 years (median, 22 years) was documented for six workers for whom archived serum samples were available, demonstrating long-standing SFV infection. All 10 persons reported general good health, and secondary transmission of SFV was not observed in three wives available for WB and PCR testing. Additional phylogenetic analysis of int and gag sequences provided the first direct evidence identifying the source chimpanzees of the SFV infection in two workers. This study documents more frequent infection with SFV than with other simian retroviruses in persons working with NHPs and provides important information on the natural history and species origin of these infections. Our data highlight the importance of studies to better define the public health implications of zoonotic SFV infections.

Animals↗
PubMed1984

Renal effects of volume expansion in the renal-denervated nonhuman primate.

Experiments were performed to determine the role of renal nerves in mediating the renal excretory effects of volume expansion in the nonhuman primate. Male Macaca fascicularis monkeys underwent chronic bilateral renal denervation or sham surgery. After a 1- to 2-wk recovery period, each animal was anesthetized with pentobarbital sodium and volume expanded 20% of estimated blood volume. Two types of volume expansion were used, a hemodilutional expansion using 6% dextran in isotonic saline and an isohemic expansion using each monkey's own blood that had previously been withdrawn in exchange for dextran. Renal denervation did not attenuate the excretory responses to volume expansion in that similar increases in urine flow, sodium excretion, filtered load of sodium excreted, osmolar and free water clearances occurred in both the renal-denervated and sham-operated groups. The onset of the responses was not delayed by renal denervation. Furthermore, the results were the same with both volume expansions. These results suggest that, in the monkey, decreases in renal nerve activity that occur with volume expansion are not necessary for eliciting the excretory responses to this hypervolemic stimulus or that other factors compensate if the kidneys are chronically denervated. In addition, the failure of renal denervation to attenuate the excretory effects of a cell-free volume expansion is not related to any dilutional characteristics of the expansion.

Animals↗
PubMed2003

Positive reinforcement training as a technique to alter nonhuman primate behavior: quantitative assessments of effectiveness.

Many suggest that operant conditioning techniques can be applied successfully to improve the behavioral management of nonhuman primates in research settings. However, relatively little empirical data exist to support this claim. This article is a review of several studies that discussed applied positive reinforcement training techniques (PRT) on breeding/research colonies of rhesus macaques (Macaca mulatta) and chimpanzees (Pan troglodytes) at The University of Texas M. D. Anderson Cancer Center and measured their effectiveness. Empirical analyses quantified the amount of time required to train rhesus monkeys to come up, station, target, and stay. Additionally, a study found that time spent affiliating by female rhesus was changed as a function of training low affiliators to affiliate more and high affiliators to affiliate less. Another study successfully trained chimpanzees to feed without fighting and to come inside on command. PRT is an important behavioral management tool that can improve the care and welfare of primates in captivity. Published empirical findings are essential for managers to assess objectively the utility of positive reinforcement training techniques in enhancing captive management and research procedures.

Animal Husbandry↗
PubMed1977

Measurement of hemolytic complement and the third component of complement in nonhuman primates.

Complement, determined by hemolytic assay, and the third component of complement (C3), determined by radial immunodiffusion assay, were measured in nine nonhuman primate species. The species studied were the titi (Callicebus mollach). The sooty mangabey (Cercocebus atys), the thick-tailed galago or bushbaby (Galago crassicaudatus panganiensis), the crab-eating monkey (Macaca fascicularis), the rhesus monkey (Macaca mulatta), the bonnet monkey (Macaca radiata), the stumptailed macaque (Macaca speciosa), the yellow baboon (Papio cynocephalus), and the black-and-red tamarin (Saguinus nigricollis). Both sheep and bovine erythrocytes were used in the hemolytic complement assays. With the sheep erythrocyte system, sera from four species (yellow baboon, sooty mangabey, bonnet monkey, black-and-red tamarin) had similar titers with both antibody sensitized and non-sensitized erythrocytes. In contrast, the titers obtained using sensitized bovine erythrocytes was always higher than the values obtained using non-sensitized bovine erythrocytes. In all species, the titers for non-sensitized sheep erythrocytes was higher than the titer for non-sensitized bovine erythrocytes. When the species were compared for cross reactivity using the radial immunodiffusion assay for human C3, the rhesus monkey showed the strongest cross reaction; the thick-tailed galago, a prosimian, showed no detectable cross reactivity; and the other species examined showed intermediate degrees of reactivity.

Animals↗
PubMed1982

Mycotic infections of the alimentary tract of nonhuman primates: a review.

Lesions of candidiasis, mucormycosis (phycomycosis), entomophthoramycosis, geotrichosis, cryptococcosis, paracoccidioidomycosis and coccidioidomycosis have been reported in the alimentary tract of nonhuman primates. Candidiasis and mucormycosis were reported most often. Both Old and New World monkeys and great apes are susceptible; infection is rare in prosimians. Ulcers and necrosis of the mucosa of the alimentary tract are the principal gross lesions. A granulomatous inflammatory process occurs in which the fungi are visible histologically on hematoxylin and eosin (HE)-stained sections, but they are seen and characterized better when stained with periodic acid-Schiff (PAS) or Gomori methenamine silver (GMS) techniques. Cultural or immunofluorescence studies, or both, are necessary for specific identification of the fungi. Immunosuppression is suggested as a predisposing factor in certain mycotic diseases.

Animals↗
PubMed1982

Hypersensitivity pneumonitis in nonhuman primates. I. Studies on the relationship of immunoregulation and disease activity.

We investigated the relationship of immunoregulation to disease activity in a nonhuman primate model of pigeon breeder's disease. Two Macaca arctoides monkeys developed classical symptoms of hypersensitivity pneumonitis after sensitization and prolonged bronchial challenge, whereas 2 other monkeys remained asymptomatic after in vivo challenge. There were no differences in the percentages of T cells, B cells, monocytes, or FC gamma-bearing T cells between symptomatic and asymptomatic animals. Nonetheless, we found a population of concanavalin A-induced, pigeon serum- (PS) induced, and spontaneous T cells that functioned as suppressor cells in autologous in vitro co-cultures in asymptomatic animals that were missing or nonfunctional in symptomatic animals. Monocyte suppressors functioned in both groups. We used low-dose total body irradiation (TBI) to inactivate T suppressor cells. Fifteen radiation units of TBI caused no change in the physical activity, routine chemistries, or blood counts of the 4 animals. After TBI, however, the previously asymptomatic animals developed fever, tachypnea, and signs of pulmonary congestion after in vivo challenge with PS. There was no change in the response to challenge in the symptomatic group. This altered response to in vivo challenge in the previously asymptomatic group persisted for 2 wk after TBI. During this period the difference in vitro immunoregulatory activity between Con A-induced, PS-induced, and spontaneous T cells in symptomatic and asymptomatic animals disappeared. Monocyte suppressors, however, continued to function in both groups after TBI. These data suggest that the monkey is an appropriate model for studies of human HP and that T cell immunoregulation may be an important element in the pathogenesis and disease activity of HP.

Alveolitis, Extrinsic Allergic↗
PubMed1983

Cerebrospinal fluid and plasma pharmacokinetics of high doses of 1-beta-D-arabinofuranosylcytosine in nonhuman primates.

The pharmacokinetics of 1-beta-D-arabinofuranosylcytosine (ara-C) in plasma, cerebrospinal fluid (CSF), and urine was studied in nonhuman primates. Conventional and high-dose schedules of ara-C were administered i.v. and intraventricularly through indwelling Ommaya reservoirs. ara-C and its metabolite 1-beta-D-arabinofuranosyluracil (ara-U) were measured by high-pressure liquid chromatography. Due to rapid peripheral deamination (230 nm ara-C/hr/ml plasma), the half-life of ara-C in plasma after a 140-mg/kg i.v. 1-hr infusion was short (3.7 min). Peak plasma concentrations of ara-C, ranging between less than 0.1 and 49 micrograms/ml, were dose dependent (ara-C, 15 to 140 mg/kg). Under these conditions, ara-C was undetectable in CSF. About 53% of the administered dose (140 mg/kg) was excreted in urine during the first 5 hr mostly as ara-U. Intraventricular administration of 50 and 250 mg of ara-C resulted in peak lumbar CSF levels of 435 and 2235 micrograms/ml, respectively, at about 155 and 80 min postinjection. Concomitant ara-U levels were one-tenth of those of ara-C and increased progressively, suggesting deamination of the drug in the central nervous system. The half-life of ara-C in CSF ranged between 50 and 60 min. Administration of 50 mg of ara-U intraventricularly resulted in peak lumbar ara-U levels of 595 micrograms/ml at about 180 min with a prolonged clearance. Concomitant plasma levels throughout the study were less than 0.1 micrograms/ml, suggesting slower equilibrium. No hematological or nervous system toxicity was observed during these studies. The clinical implications of these findings are discussed.

Animals↗
PubMed1982

Mycotic infections of the alimentary tract of nonhuman primates: a review.

Lesions of candidiasis, mucormycosis (phycomycosis), entomophthoramycosis, geotrichosis, cryptococcosis, paracoccidioidomycosis and coccidioidomycosis have been reported in the alimentary tract of nonhuman primates. Candidiasis and mucormycosis were reported most often. Both Old and New World monkeys and great apes are susceptible; infection is rare in prosimians. Ulcers and necrosis of the mucosa of the alimentary tract are the principal gross lesions. A granulomatous inflammatory process occurs in which the fungi are visible histologically on hematoxylin and eosin (HE)-stained sections, but they are seen and characterized better when stained with periodic acid-Schiff (PAS) or Gomori methenamine silver (GMS) techniques. Cultural or immunofluorescence studies, or both, are necessary for specific identification of the fungi. Immunosuppression is suggested as a predisposing factor in certain mycotic diseases.

Animals↗
PubMed1981

Computer-based animal record system in a nonhuman primate colony.

A relatively inexpensive microcomputer system was developed to store and manipulate clinical and pathologic data from a large colony of nonhuman primates. The programming for the system was designed so that the computer instructs users, who may have no knowledge of programming, how to enter data of all kinds and how to to command it to answer any ad hoc queries about the data. Minimum input from a professional programmer is required. As many as 4 investigators may use the system simultaneously by means of satellite terminals located in several areas throughout the facility. Most alphabetic data are coded, using 2- or 3-digit codes. More complex diagnostic data are coded, using the numeric codes of the Systematized Nomenclature of Medicine. presently, 17 record types encompasses all data entered into the computer. The system is functionally designed and about 50% operational at this time. This is the first description of an animal medical data system designed to exploit the lower costs and increased power of commercially available microcomputer packages.

Animals↗
PubMedDate not supplied

Trace level determination of doxylamine in nonhuman primate plasma and urine by GC/NPD and HPLC.

Bendectin contains doxylamine succinate and is used for the treatment of nausea and vomiting in pregnant women. Trace level analytical chemical procedures for analysis of doxylamine in primate urine and plasma were required before toxicological tests with the drug in three species of nonhuman primates could be performed. A gas chromatographic procedure using a nitrogen phosphorus detector was developed to quantitate doxylamine in primate plasma at levels as low as 100 ppb. A high-pressure liquid chromatographic procedure was also developed to assay the drug in primate urine at levels as low as 250 ppb. Data from stability studies with the drug in plasma at -5 degrees and -20 degrees C, and recovery of the drug from Bendectin tablets, plasma, and urine are also presented.

Animals↗
PubMed1998

Plasma and cerebrospinal fluid pharmacokinetics of 9-aminocamptothecin (9-AC), irinotecan (CPT-11), and SN-38 in nonhuman primates.

PURPOSE: The plasma and cerebrospinal fluid (CSF) pharmacokinetics of the camptothecin analogs, 9-aminocamptothecin (9-AC) and irinotecan, were studied in a nonhuman primate model to determine their CSF penetration. METHODS: 9-AC, 0.2 mg/kg (4 mg/m2) or 0.5 mg/kg (10 mg/m2), was infused intravenously over 15 min and irinotecan, 4.8 mg/kg (96 mg/m2) or 11.6 mg/kg (225 mg/m2), was infused over 30 min. Plasma and CSF samples were obtained at frequent intervals over 24 h. Lactone and total drug forms of 9-AC, irinotecan, and the active metabolite of irinotecan, SN-38, were quantified by reverse-phase HPLC. RESULTS: 9-AC lactone had a clearance (CL) of 2.1 +/- 0.9 l/kg per h, a volume of distribution at steady state (Vd[ss]) of 1.6 +/- 0.7 l/kg and a half-life (t1/2) of 3.2 +/- 0.8 h. The lactone form of 9-AC accounted for 26 +/- 7% of the total drug in plasma. The CSF penetration of 9-AC lactone was limited. CSF 9-AC lactone concentration peaked 30 to 45 min after the dose at 11 to 21 nM (0.5 mg/kg dose), and the ratio of the areas under the CSF and plasma concentration-time curves (AUC(CSF):AUC[P]) was only 3.5 +/- 2.1%. For irinotecan, the CL was 3.4 +/- 0.4 l/kg per h, the Vd(ss) was 7.1 +/- 1.3 l/kg, and the t1/2 was 4.9 +/- 2.2 h. Plasma AUCs of the lactone form of SN-38 were only 2.0% to 2.4% of the AUCs of irinotecan lactone. The lactone form of irinotecan accounted for 26 +/- 5% of the total drug in plasma, and the lactone form of SN-38 accounted for 55 +/- 6% of the total SN-38 in plasma. The AUC(CSF):AUC(P) ratio for irinotecan lactone was 14 +/- 3%. SN-38 lactone and carboxylate could not be measured (< 1.0 nM) in CSF. The AUC(CSF):AUC(P) ratio for SN-38 lactone was estimated to be < or = 8%. CONCLUSION: Despite their structural similarity, the CSF penetration of 9-AC and SN-38 is substantially less than that of topotecan which we previously found to have an AUC(CSF):AUC(P) ratio of 32%.

Animals↗
PubMed1983

Bladder and ureteral pressure relationships in nonhuman primates.

Bladder pressures during filling are precisely paralleled by ureteral resistance to perfusion. The pressure relationships are identical in normal, spinal and decentralized nonhuman primates, none of which had vesicoureteral reflux. Intravesical and thus intraureteral pressures are higher in animals with neurological lesions, particularly decentralization.

Animals↗
PubMed1997

Effect of enalapril therapy on glomerular accumulation of immune complexes and mesangial matrix in experimental glomerulonephritis in the nonhuman primate.

The present study is a prospective, controlled, blinded trial of enalapril therapy in experimental immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate (cynomolgus monkey [CYN]). Two groups of CYNs were studied: those with established GN (study A) and those in which GN was being induced (study B). In study A, 12 CYNs had GN established by 8 or 10 weeks of daily intravenous infusion of bovine gamma-globulin (BGG). These CYNs were then assigned to either 4 weeks of daily oral enalapril therapy (n = 6) or daily oral placebo therapy (n = 6). The daily BGG infusions were continued during the 4 weeks of enalapril or placebo therapy. At the start of the enalapril/placebo protocol, the two groups were similar with respect to proteinuria and level of precipitating antibody to BGG, which determined the daily BGG dose. Renal biopsy was performed in each CYN at the start and end of the 4-week period of enalapril/placebo protocol. In study B, 15 normal CYNs were immunized to BGG over a period of 4 weeks. The CYNs were then assigned to daily oral enalapril therapy (n = 8) or placebo therapy (n = 7) based on level of precipitating antibody to BGG. At this point, daily intravenous BGG was begun along with daily enalapril or placebo for 8 weeks. Renal biopsy was performed in each CYN before and at the end of this 8-week period. In study A, enalapril therapy was associated with a significant decrease in mesangial matrix volume (mean change, -27.7%; P = 0.031) and a trend toward decreased mesangial matrix deposits (mean change, -34.1%; P = 0.188). By contrast, in CYNs receiving placebo therapy, mesangial matrix volume increased compared with the enalapril group (P = 0.002) and mesangial deposits were unchanged. In study B, both the enalapril and placebo groups showed significant increases in mesangial matrix volume, mesangial deposits, mesangial cell volume, and capillary wall deposits during the 8 weeks of daily BGG infusion. However, none of the differences between the groups achieved statistical significance. Changes in mesangial cell volume and capillary wall deposits were also evaluated in study A and study B, but were not found to be different between the enalapril and placebo groups. In both study A and study B, blood pressure was lower in the enalapril groups. In conclusion, in the initial phase of IC-GN induction (0 to 8 weeks), enalapril therapy does not significantly influence the glomerular accumulation of mesangial matrix or immune deposits. However, in established IC-GN (after 8 weeks of GN induction), enalapril therapy significantly decreases the further accumulation of mesangial matrix and may decrease the further accumulation of mesangial deposits. Whether this benefit of enalapril therapy was related to lower blood pressure or to other effects of angiotensin-converting enzyme (ACE) inhibition was not determined in this study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Effects of abciximab on the acute pathology of blood vessels after arterial stenting in nonhuman primates.

OBJECTIVES: This study was designed to assess the effect of abciximab on platelet and leukocyte deposition 60 min after stent insertion in nonhuman primates. BACKGROUND: Although it is well established that abciximab improves both short- and long-term clinical outcomes after stent placement, there have been no studies assessing its effect on early platelet and leukocyte deposition. METHODS: Cynomolgus monkeys were pretreated with aspirin and either saline or a 0.4 mg/kg bolus of abciximab, and then subjected to angioplasty and Palmaz-Schatz stent placement in the common iliac artery or abdominal aorta. After 60 min, animals were euthanized and the stented artery was evaluated by immunohistochemistry and morphometry. RESULTS: Complete occlusion of the stented vessel with a thin fibrin(ogen) meshwork and trapped blood occurred in two saline-treated and two abciximab-treated animals. In the four remaining saline-treated animals, a layer of erythrocytes trapped in a network of fibrin(ogen) was noted close to the vessel wall, and this was covered by a layer of large, irregular platelet thrombi. Leukocytes formed a monolayer on top of the platelets and near stent struts. In the four remaining abciximab-treated animals, the mean erythrocyte area was 65% smaller (p = 0.070), the platelet aggregate area was 89% smaller (p = 0.049) and the luminal area was 59% larger (p = 0.004). A monolayer of leukocytes also formed on top of the platelets and near stent struts. CONCLUSIONS: In control stented blood vessels in this study, platelet thrombi formed not at the vessel wall, but on top of an erythrocyte-rich layer, and platelets recruited leukocytes. Abciximab decreased the size of platelet thrombi, but did not prevent leukocyte recruitment.

Abciximab↗
PubMed2005

Failure of remyelination in the nonhuman primate optic nerve.

The mechanisms limiting myelin repair in human central nervous system (CNS) remain unknown. Models of induced-demyelination in the nonhuman primate CNS may provide the necessary grounds to unravel these mechanisms and to investigate the development of strategies to promote myelin repair. To address this issue, we developed a model of focal demyelination in the adult Macaca fascicularis CNS. Lesions were induced by microinjection of lysolecithin in the optic nerve and the profile of remyelination was compared to that of lysolecithin-induced lesions of the spinal cord. In both structures, the time-course of demyelination as well as the onset of remyelination were found to be similar to that in the rodent CNS. While spinal cord lesions were remyelinated within 6 weeks, optic nerve lesions remained demyelinated for up to 3 months post-injection. The failure of remyelination in the optic nerve correlated with a reduced density of NG2+ oligodendrocyte progenitor cells, the presence of oligodendrocytes that fail to ensheath naked axons in the lesion and the absence of astrocyte recruitment in the lesion compared with spinal cord lesions. Our present data suggest that the reduced oligodendrocyte progenitor population, the improper activation of oligodendrocytes at the onset of remyelination in the optic nerve, and possibly, the involvement of astrocytes contribute to the chronicity of the optic nerve lesion. This model of chronic demyelination in the macaque optic nerve stresses its pertinence to unraveling the mechanisms limiting remyelination in multiple sclerosis.

Animals↗
PubMed2002

Pancreatic islet transplantation using the nonhuman primate (rhesus) model predicts that the portal vein is superior to the celiac artery as the islet infusion site.

We've established a nonhuman primate islet allotransplant model to address questions such as whether transplanting islets into the gut's arterial system would more safely and as effectively support long-term islet allograft survival compared with the traditional portal vein approach. We reasoned that islets make up <2% of pancreatic cell mass but consume an estimated 20% of arterial blood flow, suggesting an advantage for the arterial site. Access to the arterial system is also easier and safer than the portal system. Pancreatectomized rhesus macaques were transplanted with allogeneic islets infused into either the portal vein (n = 6) or the celiac artery (n = 4). To prevent rejection, primates were given daclizumab, tacrolimus, and rapamycin. In five of six portal vein experiments, animals achieved normoglycemia without exogenous insulin. In contrast, none of the animals given intra-arterial islets showed even transient insulin independence (P = 0.048). Two of the latter animals received a second islet transplant, this time to the portal system, and both achieved insulin independence. Thus, intraportal islet transplantation under conventional immunosuppression is feasible in primates and can result in long-term insulin independence when adequate immunosuppression is maintained. Arterial islet injection, however, does not appear to be a viable islet transplantation technique.

Animals↗