Biomedical subjects

R Khanna

Publications and source records attributed to R Khanna.

At least 19 recordsLinked to original sources

PubMed1996

Recruitment during infectious mononucleosis of CD3+CD4+CD8+ virus-specific cytotoxic T cells which recognise Epstein-Barr virus lytic antigen BHRF1.

Epstein-Barr virus (EBV) is the aetiological agent of infectious mononucleosis (IM) which is a common sequel to primary EBV infection. Thereafter, the virus is maintained as a lifetime latent infection. Although the proteins expressed during the latent EBV infection provide a rich source of immunogenic epitopes, very little is known about cytotoxic T lymphocyte (CTL) control of primary EBV infection. The present report is based on an analysis of CTL clones derived from a patient suffering from acute IM. An intriguing feature of six CTL clones that displayed an HLA-restricted pattern of cell lysis was their initial coexpression of the T cell markers CD3, CD4, and CD8. Detailed analysis of one of these clones, which was restricted through the class II MHC antigen DR2, revealed reactivity with an epitope within the EBV lytic cycle early antigen, BHRF-1, which corresponds to the C-terminal region of the protein (AGLTLSLLVICSYLFISRG) (residues 171-189). There have been no previously published reports describing a CTL response during acute IM directed against an EBV lytic antigen. Interestingly, the coexpression of CD4 and CD8 by these CTLs during acute IM suggests that CD3+CD4+CD8+ cortical thymocytic precursor cells are recruited in order to overcome the EBV infection.

Acute Disease↗

PubMed1996

Four-year experience with swan neck presternal peritoneal dialysis catheter.

The swan neck presternal catheter is composed of two flexible (silicon rubber) tubes joined by a titanium connector at the time of implantation. The exit site is located in the presternal or parasternal area. The catheter located on the chest was designed to reduce the incidence of exit site infections compared with peritoneal dialysis catheters with abdominal exit sites. From August 1991 to May 1995, 24 swan neck presternal catheters have been implanted in 24 patients for the following reasons: obesity nine patients, ostomies three patients, a suprapubic catheter one patient, previous problems with abdominal catheters two patients, desire to use a bathtub five patients, need to use a whirlpool one patient, need to wear sweatpants with an elastic waistband one patient, and body image two patients. In the same period, 47 abdominal swan neck catheters were implanted in 44 patients who preferred catheters with the exit on the abdomen. Presternal catheters tended to perform better regarding exit and tunnel infections, even though they were implanted in several patients in whom regular catheters with the exit on the abdomen would be difficult or impossible to implant. Two-year survival probability of presternal catheters was 0.88 +/- 0.14 (+/- SE). Recurrent/refractory peritonitis was the only reason of catheter failure. The differences in results between presternal and abdominal catheters were statistically insignificant; only the use of antibiotics to treat exit site infection was significantly higher with abdominal catheters. Patient acceptance of the exit position was good; at least seven patients preferred presternal catheter for psychological or body image reasons. We conclude that the swan neck presternal catheters provide excellent results comparable to those achieved with swan neck abdominal catheters. The catheter seems suitable for any patient commencing peritoneal dialysis and is particularly useful in extremely obese patients (body mass index > 40 kg/m2) and those with ostomies. The catheter exit location in the chest may be preferred by some patients, both men and women, for psychological or body image reasons. No specific contraindications to the presternal catheter implantation have been identified.

Abdomen↗

PubMed1996

Unusually high frequency of Epstein-Barr virus genetic variants in Papua New Guinea that can escape cytotoxic T-cell recognition: implications for virus evolution.

Cytotoxic T lymphocytes (CTLs) which recognize viral antigens in association with human leukocyte antigens (HLAs) play an important role in controlling persistent virus infections. These viruses use several mechanisms to evade the immune response, including mutations that affect either T-cell receptor recognition or binding of viral epitopes to the HLA. It has recently been proposed that the distribution of HLA frequencies and the specific CTL response may influence the long-term evolution of Epstein-Barr virus (EBV) by selecting variants which lack immunodominant CTL epitopes. To test this hypothesis, we have studied EBV isolates from two genetically distinct Papua New Guinea (PNG) populations, residing in coastal and highland regions, for polymorphism within seven viral CTL epitope sequences restricted through several class I HLAs. Surprisingly, all EBV isolates analyzed displayed identical amino acid substitutions within HLA A11-, B35- and B8-restricted CTL epitope sequences which completely abrogated CTL recognition and binding of synthetic peptides to HLA molecules. Furthermore, these substitutions revealed no correlation with the contemporary distribution of HLAs in the different PNG populations, which argues for a minimal influence of immune pressure. The sequence homology between EBV isolates from coastal and highland PNG suggests that the virus may have had a single origin and, more importantly, that these isolates are genetically distinct from those present in a Caucasian population.

Amino Acid Sequence↗

PubMed1995

Isolation of cytotoxic T lymphocytes from healthy seropositive individuals specific for peptide epitopes from Epstein-Barr virus nuclear antigen 1: implications for viral persistence and tumor surveillance.

The question of whether Epstein-Barr nuclear antigen 1 (EBNA1) includes cytotoxic T lymphocyte (CTL) epitopes has generated considerable scientific interest, primarily due to its important implications for the overall biology of Epstein-Barr virus (EBV). Earlier studies have suggested that EBV-associated malignancies that express only EBNA1 escape virus-specific immune surveillance since this antigen is not a target for CTL recognition. In the present report we have used a modified protocol to demonstrate that EBNA1 includes sequences which can be recognized by both polyclonal and clonal CTLs. CD4+ CTL clones were isolated from a healthy, seropositive donor that recognized the peptide epitope TSLYNLRRGTALA from EBNA1 in association with HLA DR1. Interestingly, these CTLs are unable to lyse EBV-infected B cells suggesting that EBNA1 may not be endogenously processed and/or presented to the host CTL response. Despite recent suggestions that glycine-alanine repeat sequences within EBNA1 can inhibit endogenous processing, target cells infected with recombinant vaccinia vectors encoding truncated EBNA1 proteins, without these repeat sequences, were not recognized by this CTL clone. Thus it seems that the presence of glycine-alanine repeats is not responsible for inhibiting the processing of the class II-restricted epitope defined in this study. These results substantiate the view that EBV-infected normal and malignant cells, where viral gene expression is limited to EBNA1, can resist CTL-mediated immune surveillance in vivo.

Amino Acid Sequence↗

PubMed1995

T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen.

Two unusual characteristics of the memory response to the immunodominant Epstein-Barr virus (EBV) epitope FLRGRAYGL, which associates with HLA B8, have provided an unique opportunity to investigate self tolerance and T cell receptor (TCR) plasticity in humans. First, the response is exceptionally restricted, dominated by cytotoxic T lymphocytes (CTL) with identical TCR protein sequences (Argaet, V. P., C. W. Schmidt, S. R. Burrows, S. L. Silins, M. G. Kurilla, D. L. Doolan, A. Suhrbier, D. J. Moss, E. Kieff, T. B. Sculley, and I. S. Misko. 1994. J. Exp. Med. 180:2335-2340). Second, CTL expressing this receptor are cross-reactive with the alloantigen HLA B* 4402 on uninfected cells (Burrows, S. R., R. Khanna, J. M. Burrows, and D. J. Moss. 1994. J. Exp. Med. 179:1155-1161). No CTL using this conserved public TCR could be reactivated from the peripheral blood of EBV exposed individuals expressing both HLA B8 and B*4402, demonstrating the clonal inactivation of potentially self-reactive T cells in humans. A significant FLRGRAYGL-specific response was still apparent, however, and TCR sequence analysis of multiple CTL clones revealed an oligoclonal TCR repertoire for this determinant within these individuals, using diverse V and J gene segments and CDR3 regions. In addition, a significant public TCR component was identified in which several distinct alpha/beta rearrangements are shared by CTL clones from a number of unrelated HLA B8+, B*4402+ donors. The striking dominance of public TCR in the response to this EBV epitope suggests a strong genetic bias in TCR gene recombination. Fine specificity analysis using peptide analogues showed that, of six different antigen receptors for FLRGRAYGL/HLA B8, none associate closely with the peptide's full array of potential TCR contact residues. Whereas the HLA B*4402-cross-reactive receptor binds amino acids toward the COOH terminus of the peptide, others preferentially favor an NH2-terminal determinant, presumably evading an area that mimics a structure presented on HLA B*4402. Thus, tolerance to a background major histocompatibility antigen can effectively diversify the TCR repertoire for a foreign epitope by deflecting the response away from an immunodominant combination of TCR-binding residues.

Amino Acid Sequence↗

PubMed1995

Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: implications for vaccine design.

The epitopes recognized by CD8+ cytotoxic T lymphocytes (CTL) are generated from cytosolic proteins by proteolytic processing. The nature of the influences exerted by the sequences flanking CTL epitopes on these processing events remains controversial. Here we show that each epitope within an artificial polyepitope protein containing nine minimal CD8+ CTL epitopes in sequence was processed and presented to appropriate CTL clones. Natural flanking sequences were thus not required to direct class I proteolytic processing. In addition, unnatural flanking sequences containing other CTL epitopes did not interfere with processing. The ability of every CTL epitope to be effectively processed from a protein containing only CTL epitopes is likely to find application in the construction of recombinant polyepitope CTL vaccines.

Amino Acid Sequence↗

PubMed1995

Epstein-Barr virus isolates with the major HLA B35.01-restricted cytotoxic T lymphocyte epitope are prevalent in a highly B35.01-positive African population.

An influence of cytotoxic T lymphocyte (CTL) response over Epstein-Barr virus (EBV) evolution was first suggested by the finding that virus isolates from highly HLA-A11-positive Oriental populations were specifically mutated in two immunodominant A11-restricted CTL epitopes. Here we turn to a second HLA allele, B35.01 and show that B35.01-restricted CTL responses in Caucasian donors reproducibly map to a single peptide epitope, YPLHEQHGM, representing residues 458-466 of the type 1 EBV nuclear antigen 3A protein (B95.8 strain). In this case, however, most EBV isolates from a highly B35.01-positive population (in The Gambia) either retained the CTL epitope sequence or carried a mutation (P-->S at position 2) which conserved antigenicity; changes leading to reduced antigenicity (Y-->N at position 1) were found in only a minority of cases. Furthermore, CTL recognizing the YPLHEQHGM epitope could be reactivated from the blood of some B35.01-positive Gambian donors by in vitro stimulation with the synthetic peptide, indicating that epitope-specific immunity does exist in this population. Possible differences between the A11-based and B35.01-based studies are discussed.

Amino Acid Sequence↗

PubMed1995

Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression.

Group I Burkitt lymphoma (BL) lines retaining the original BL tumor cell phenotype are unable to present endogenously expressed antigens to HLA class I-restricted cytotoxic T cells (CTL) but can be recognized if the relevant HLA class I/peptide epitope complex is reconstituted at the cell surface by exogenous addition of synthetic target peptide. Endogenous antigen-processing function is restored in BL lines that have undergone Epstein-Barr virus (EBV)-induced drift in culture to the group III phenotype typically displayed by EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin. We compared group I versus group III cells for their expression of proteasome components, transporter proteins and HLA-class I antigens, all of which are thought to be involved in the endogenous antigen processing pathway. By Western blot analysis, there were not consistent differences in the low molecular mass protein subunits of proteasomes (lmp)-2, lmp-7 and delta, although the mb-1 proteasome subunit was regularly present at higher levels in group I BL lines relative to group III lines or LCL. By contrast there were marked differences in the expression of peptide transporter-associated proteins (Tap), with down-regulation of Tap-1 and Tap-2 in 8/8 and 7/8 group I BL lines, respectively. Surface levels of HLA class I antigens were also consistently lower in group I cells; this was not associated with an intracellular accumulation of free HLA heavy chains, such as is seen in the Tap-deficient T2 processing-mutant line, but instead reflected a reduced rate of HLA class I synthesis in group I cells. Analysis of EBV gene transfectants of the B lymphoma lines BJAB and BL41 showed that the virus-encoded latent membrane protein-1 (LMP1), which is one of several EBV antigens expressed in group III but not in group I cells, was uniquely able to up-regulate expression both of the Tap proteins and HLA class I. Furthermore, this was accompanied by a restoration of antigen-processing function as measured by the ability of these cells to present an endogenously expressed viral antigen to CTL. These effects of LMP1 were similar to those induced in the same cell lines by interferon-gamma treatment. The results implicate both Tap and HLA class I expression as factors limiting the antigen-processing function of BL cells, and suggest that the accessibility of other EBV-associated malignancies to CTL surveillance may be critically dependent upon their LMP1 status.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Posttraumatic cerebral arterial spasm.

Posttraumatic cerebral arterial spasm (vasospasm) has been demonstrated in the past by angiography, and recently by transcranial Doppler ultrasonography. Posttraumatic vasospasm is a delayed complication that involves the large basal intracranial arteries (e.g., internal carotid, middle cerebral, basilar) and occurs in 25-40% of head trauma patient. The time course of posttraumatic vasospasm resembles that of vasospasm associated with aneurysmal subarachnoid hemorrhage with onset occurring 2 or more days after injury. A study of the relationship of admission CT scan findings to the incidence of vasospasm suggests that intradural bleeding, which extends into the CSF (subarachnoid, intraventricular, and subdural hemorrhage), plays a role in the pathogenesis of posttraumatic arterial spasm. The preliminary results of a large prospective study of head trauma patients suggest that vasospasm may be an important determinant of outcome from severe head injury.

Brain Injuries↗

PubMed1995

Immune regulation in Epstein-Barr virus-associated diseases.

Epstein-Barr virus (EBV) is a member of the human herpesvirus family and, like many other herpesviruses, maintains a lifelong latent association with B lymphocytes and a permissive association with stratified epithelium in the oropharynx. Clinical manifestations of primary EBV infection range from acute infectious mononucleosis to an asymptomatic persistent infection. EBV is also associated with a number of malignancies in humans. This review discusses features of the biology of the virus, both in cell culture systems and in the natural host, before turning to the role of the immune system in controlling EBV infection in healthy individuals and in individuals with EBV-associated diseases. Cytotoxic T cells that recognize virally determined epitopes on infected cells make up the major effector arm and control the persistent infection. In contrast, the options for immune control of EBV-associated malignancies are more restricted. Not only is antigen expression restricted to a single nuclear antigen, EBNA1, but also these tumor cells are unable to process EBV latent antigens, presumably because of a transcriptional defect in antigen-processing genes (such as TAP1 and TAP2). The likelihood of producing a vaccine capable of controlling the acute viral infection and EBV-associated malignancies is also discussed.

Antibody Formation↗

PubMed1995

Trichotillomania: symptom or syndrome? A need for revision.

A 40-year-old religious Hindu male presented with his fourth episode of mania along with repetitive plucking of hair. This unusual behaviour was explained by him as a way to 'attain divinity by discarding the impure demoniac hair'. He had not shown this symptom in the previous episodes. With treatment of the mood disorder the hair plucking also disappeared. Hair removal has an important religious-cultural meaning in eastern India. Possible implication of the symptom is discussed. A case is made for reporting hair plucking as a symptom rather than a syndrome and it may at times represent a culture-specific symptom.

Adult↗

PubMed1995

Expected white blood cell counts and differentials in a rat model of peritoneal dialysis.

OBJECTIVE: The purpose of this study was to establish baseline dialysate white blood cell (WBC) counts and differentials in noninfected rats on peritoneal dialysis (PD). DESIGN: Sixteen male Sprague-Dawley rats underwent PD in the first protocol, and eight from the 16 continued PD in the second through fourth protocols. At the beginning of the experiments, all animals had a PD catheter implanted and were initiated on PD with 1.5% dextrose dialysis solution twice daily. In the first protocol, WBC counts and differentials were assessed from day 4 to day 15 of dialysis in noninfected animals to establish "normal values" for such a rat model. In protocol 2, WBC counts and solute concentrations in small aliquots of dialysate obtained from the catheter were compared to values in well-mixed total drainage. Protocol 3 was designed to assess effects of dwell time on WBC counts. Protocol 4 examined the effect of glucose concentration of dialysis solution on WBC counts. RESULTS: In the first protocol, the mean dialysate WBC counts were significantly higher on the fourth day of dialysis, but stabilized below 2500 cells/mm3 by the eighth day. The percentage of neutrophils was stable around 20%-25%. In the second protocol, we found aliquots < 1 mL might underestimate the dialysate WBC count compared to the complete drainage. In the third protocol, WBC counts increased as cycle time became longer, but the percentage of neutrophils remained below 50%. In the fourth protocol, we did not find any effects of glucose concentration of instilled solutions on WBC counts and differentials. CONCLUSION: This study of WBC counts and differentials in noninfected rats on peritoneal dialysis establishes the range above which infection should be suspected. WBC counts increase with cycle time. Small dialysate aliquots may underestimate WBC counts. Glucose concentration does not effect WBC counts.

Animals↗

PubMed1995

Predicted and measured daily creatinine production in CAPD: identifying noncompliance.

OBJECTIVE: To evaluate the ratio of measured creatinine (Cr) production to predicted creatinine production as an index of noncompliance in patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A cross-sectional analysis. PATIENTS: One hundred and twenty-one patients on CAPD. MEASUREMENTS: We have calculated Cr production from measured Cr outputs in 24-hour collections of urine and dialysate. Predicted Cr productions were calculated from standard tables. Weekly KT/V urea and weekly Cr clearances were determined from the same 24-hour urine and dialysate collections. Lean body mass (LBM) was calculated from the Cr production. Serum albumin concentration was measured. RESULTS: The ratio of measured/predicted Cr production correlated positively and significantly with weekly KT/V urea, the protein equivalent of nitrogen appearance (PNA), weekly Cr clearance, and LBM. There was a decline in serum albumin concentration at ratios greater than 1.24, supporting the opinions of previous authors who have suggested that ratios greater than 1.24 are highly suggestive of noncompliance with the dialysis prescription. Defining noncompliance as a ratio greater than 1.24 implied that at least 5% of the female and 17% of the male patients were noncompliant. CONCLUSIONS: Declining serum albumin concentrations at higher ratios of measured/predicted Cr production support the opinion that this is an index of noncompliance. However, not all noncompliant patients necessarily have a ratio greater than 1.24. Weekly KT/V urea, weekly Ccr and LBM are all artifactually increased by "washout effects" if all exchanges are done only or mainly on the collection day.

Body Mass Index↗

PubMed1995

Continuous ambulatory peritoneal dialysis and the heart.

OBJECTIVE: To review clinical research pertaining to continuous ambulatory peritoneal dialysis (CAPD) and the heart. DATA SOURCES: A Medline computer search was employed to identify appropriate references from 1970 - 1994. Indexing terms were: continuous ambulatory peritoneal dialysis, hemodialysis, heart or cardiac, left ventricle, coronary artery disease, and survival. English and non-English language abstracts were scrutinized. STUDY SELECTION: Forty-six studies were reviewed and utilized. Numerical data extracted are reported in this review as they were reported in the original article. RESULTS: This review provides a broad-based survey of studies pertaining to CAPD and the heart. Most of the studies relate to CAPD and left ventricular structure or function. Little information exists concerning CAPD and coronary artery disease, valvular disease, pericardial disease, and cardiac arrhythmias. Studies pertaining to patient survival on CAPD identify coronary artery disease and congestive heart failure as major risk factors, but in-depth quantification of these cardiovascular disorders is lacking in the literature. CONCLUSIONS: CAPD is capable of decreasing left ventricular (LV) volume and improving LV systolic function in patients with LV enlargement and those with LV systolic dysfunction. The effect of CAPD on left ventricular hypertrophy (LVH) and LV diastolic function is variable. CAPD produces symptomatic improvement in patients with refractory congestive heart failure, but its effect on survival in such patients is uncertain. Atherogenic lipid abnormalities occur in CAPD patients. The clinical significance of these abnormalities is uncertain. Coronary artery bypass surgery can be performed safely and effectively on CAPD patients. CAPD is not arrhythmogenic. Survival of CAPD patients is similar to that of hemodialysis patients except in elderly diabetics for whom it is slightly lower.

Arrhythmias, Cardiac↗

PubMed1995

Preliminary evaluation of silver-coated peritoneal catheters in rats.

Silver is known to have powerful antibacterial properties against a variety of micro-organisms and has a low toxicity and a favorable biocompatibility profile. This study was designed to evaluate the effectiveness of silver-coated catheters in preventing early exit-site infection and to assess tunnel morphology. Seven male Sprague-Dawley rats underwent simultaneous implantation of two double-cuffed, silver-coated silicone rubber and standard silicone rubber catheters. Weekly observations and photographs documented exit-site characteristics. The animals were sacrificed and catheters removed and processed for histopathology of the external tunnel at 5 weeks. Exit sites of silver-coated catheters tended to have less inflammation and infection and healed better than those of uncoated catheters; however, these data did not achieve significance using the Wilcoxon signed-rank test. Sections of the external tunnel of well-healing exit sites showed an epithelialized tract with granulation tissue near the cuff and significant invasion of the external cuff by collagen with a mild neutrophilic inflammatory response. In contrast, the histology of the external tunnel of infected exists revealed exudate overlying inflammatory granulation tissue and a variable degree of fibrosis of the cuff. When the exit sites appeared similar, no significant histopathological differences in sinus tract and cuff morphology were noted with either silver or standard catheters. In conclusion, these findings suggest that silver coating of catheters may decrease the incidence of early exit-site infections and allow better ingrowth of the catheter.

Animals↗

PubMed1995

Rat model of peritoneal fibrosis: preliminary observations.

The aim of this study was to establish a rat model of peritoneal fibrosis. After insertion of peritoneal catheters into 18 rats, the rats were divided into three groups. All animals were dialyzed twice a day with 4.25% Dianeal containing heparin. Group 1 rats (control) received antibiotics (vancomycin and gentamicin) in each exchange: group 2 rats were inoculated with Escherichia coli (5 x 10(6) in 5 mL of saline) at the beginning of the study; group 3 rats were treated with antibiotics after Escherichia coli inoculation; they also received a second inoculation of Escherichia coli after the second week of the study. By the end of the second week, group 2 rats were sacrificed because of catheter problems. Group 1 and 3 rats were sacrificed after 4 weeks of dialysis. A weekly peritoneal equilibration test (PET) was performed in each rat. The comparison of the PET results from the beginning and end of the study showed an increased permeability to glucose (p < 0.05) and total protein (p < 0.05) in group 3, which was not noted in group 1. In histology samples there was only delicate fibrosis with cellular infiltration in the peritoneum in group 1 rats. These changes were much more prominent in group 3 rats. This study suggests that E. coli peritonitis causes peritoneal fibrosis in rats, but to have a sclerosing encapsulating peritonitis (SEP) model this experiment must be carried out for a longer time.

Animals↗

PubMed1995

Spontaneous peritonitis and peritoneal fibrosis in rats on peritoneal dialysis for 9 weeks.

To investigate characteristics of peritonitis in rats on peritoneal dialysis (PD), we retrospectively studied 36 cases of peritonitis in 23 rats. After breakin dialysis postcatheter insertion, the animals were dialyzed twice daily with 1.5% or 4.25% Dianeal for 8 weeks. White blood cell (WBC) count with differentials and microbiological culture of the dialysate were examined twice weekly. Peritonitis was treated with cefazolin and tobramycin until the tenth day after the dialysate became clear. The peritoneal equilibration test (PET) was performed at weeks 2, 6, and 10. The dialysate was obtained at 0, 2, and 4 hours for glucose assay. The peritoneal cavity was inspected, and peritoneal tissue specimens were taken. There were 10 single episodes of peritonitis, 7 recurrences, and 6 reinfections. The organisms isolated were Staphylococcus aureus in 24 cases of peritonitis and Escherichia coli in 6 cases of peritonitis. The average treatment period was 16 days. The glucose absorption ratio became higher over time in single episodes of peritonitis, but was unchanged in recurrences and reinfections. Sixteen adhesions, 1 abscess, and 12 sclerotic retractions of the mesentery were observed. Fibrotic thickening of the peritoneum was found histologically in all animals. In spontaneous peritonitis in rats, we often found complicated clinical courses, catheter closure, intraperitoneal adhesion, and fibrotic thickening of the peritoneum.

Animals↗

PubMed1995

Absorption of iron dextran from the peritoneal cavity of rats.

We investigated the absorption rate and acute toxicities of intraperitoneal iron dextran in rats. Eighteen Sprague-Dawley rats were divided into three groups (n = 6). The animals were given standard 1.5% Dianeal (group 1) or 1.5% Dianeal containing iron in a concentration of 2 mg/L (group 2) or 10 mg/L (group 3) as iron dextran. First, a predialysis blood sample was obtained, and 25 mL of the designated dialysis solution was instilled into the peritoneal cavity. After a 6-hour cycle the dialysate was drained, and a postdialysis blood sample and specimen of the peritoneum were obtained. The iron concentrations of the dialysis solution, the dialysate, and both serum samples were determined. Histological samples were processed by hematoxylin and eosin and Prussian blue stain. Results of the iron concentration (mg/L) of the dialysis solution, the dialysate, and the percent of the absorbed iron were as follows: group 1: 0.00, 0.20 +/- 0.15, N/A; group 2: 2.24, 0.66 +/- 2.8, 73.8 +/- 11.0; group 3: 9.84, 2.12 +/- 0.62, 80.8 +/- 5.7. The serum iron concentration did not change. No abnormal findings were found histologically. More than 70% of the iron dextran was absorbed from the peritoneal cavity of the rats during a 6-hour peritoneal dialysis exchange. Intraperitoneal iron dextran may be an alternative route of iron delivery.

Absorption↗