Updated evidence of the effectiveness and safety of transanal drainage tube for the prevention of anastomotic leakage after rectal low anterior resection: a systematic review and meta-analysis.

BACKGROUNDS: Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy for AL prevention; however, its efficacy and safety remain contentious. METHODS: A systematic review and meta-analysis were used to evaluate the influence of TDT subsequent to LAR as part of the revision of the surgical site infection prevention guidelines of the Japanese Society of Surgical Infectious Diseases (PROSPERO registration; CRD42023476655). We searched each database, and included randomized controlled trials (RCTs) and observational studies (OBSs) comparing TDT and non-TDT outcomes. The main outcome was AL. Data were independently extracted by three authors and random-effects models were implemented. RESULTS: A total of three RCTs and 18 OBSs were included. RCTs reported no significant difference in AL rate between the TDT and non-TDT groups [relative risk (RR): 0.69, 95% confidence interval (CI) 0.42-1.15]. OBSs reported that TDT reduced AL risk [odds ratio (OR): 0.45, 95% CI 0.31-0.64]. In the subgroup excluding diverting stoma (DS), TDT significantly lowered the AL rate in RCTs (RR: 0.57, 95% CI 0.33-0.99) and OBSs (OR: 0.41, 95% CI 0.27-0.62). Reoperation rates were significantly lower in the TDT without DS groups in both RCTs (RR: 0.26, 95% CI 0.07-0.94) and OBSs (OR: 0.40, 95% CI 0.24-0.66). TDT groups exhibited a higher anastomotic bleeding rate only in RCTs (RR: 4.28, 95% CI 2.14-8.54), while shorter hospital stays were observed in RCTs [standard mean difference (SMD): -0.44, 95% CI -0.65 to -0.23] and OBSs (SMD: -0.54, 95% CI -0.97 to -0.11) compared with the non-TDT group. CONCLUSIONS: A universal TDT placement cannot be recommended for all rectal LAR patients. Some patients may benefit from TDT, such as patients without DS creation. Further investigation is necessary to identify the specific beneficiaries.

A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L.

BACKGROUND: Thymic carcinoma (TC) is an exceptionally rare tumor, which has a very poor prognosis differing from thymoma. Till date, there has been no report of any results of clinical trials focusing on TC. The role of non-anthracycline-based chemotherapy has not been elucidated since the previous studies included a relatively small number of TC patients. This single-arm study evaluated carboplatin and paclitaxel (CbP) in chemotherapy-naive patients with advanced TC. PATIENTS AND METHODS: The study treatment consisted of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point was objective response rate (ORR) by independent review. The secondary end points included overall survival (OS), progression-free survival (PFS), and safety. Based on the SWOG 2-stage design, the planned sample size of 40 patients was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05. RESULTS: Forty patients from 21 centers were enrolled for this study from May 2008 to November 2010. Of the 39 patients evaluable for analysis, 36 were pathologically diagnosed by independent review, and 97% patients were eventually TC. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval 21%-53%; P = 0.031). The median PFS was 7.5 (6.2-12.3) months, while OS did not reach the median value. Major adverse event was grade 3-4 neutropenia in 34 patients (87%). There was no treatment-related death. CONCLUSIONS: In this largest trial with TC, CbP showed promising efficacy in advanced TC when compared with anthracycline-based chemotherapy, which is the current standard treatment of thymic neoplasm. Our results established that CbP, one of the standard treatments for non-small-cell lung cancer, might be an option as a chemotherapy regimen for TC.

The effectiveness of fascial closure with antimicrobial-coated sutures in preventing incisional surgical site infections in gastrointestinal surgery: a systematic review and meta-analysis.

The aim of this study was to conduct a systematic review and meta-analysis of the efficacy of fascial closure using antimicrobial-sutures specifically for the prevention of surgical site infections (SSIs) in gastrointestinal surgery, as part of the revision of the SSI prevention guidelines of the Japanese Society of Surgical Infectious Diseases (JSSI). We searched CENTRAL, PubMed and ICHUSHI-Web in May 2023, and included randomized controlled trials (RCTs) comparing antimicrobial-coated and non-coated sutures for fascial closure in gastrointestinal surgery (PROSPERO No. CRD42023430377). Three authors independently screened the RCTs. We assessed the risk of bias and the GRADE criteria for the extracted data. The primary outcome was incisional SSI and the secondary outcomes were abdominal wall dehiscence and the length of postoperative hospital stay. This study was supported partially by the JSSI. A total of 10 RCTs and 5396 patients were included. The use of antimicrobial-coated sutures significantly lowered the risk of incisional SSIs compared with non-coated suture (risk ratio: 0.79, 95% confidence intervals: 0.64-0.98). In subgroup analyses, antimicrobial-coated sutures reduced the risk of SSIs for open surgeries, and when monofilament sutures were used. Antimicrobial-coated sutures did not reduce the incidence of abdominal wall dehiscence and the length of hospital stay compared with non-coated sutures. The certainty of the evidence was rated as moderate according to the GRADE criteria, because of risk of bias. In conclusion, the use of antimicrobial-coated sutures for fascial closure in gastrointestinal surgery is associated with a significantly lower risk of SSI than non-coated sutures.

Excessive CD4+ T cells co-expressing interleukin-17 and interferon-γ in patients with Behçet's disease.

Excessive T helper type 1 (Th1) cell activity has been reported in Behçet's disease (BD). Recently, association of Th17 cells with certain autoimmune diseases was reported, and we thus investigated circulating Th17 cells in BD. CD4(+) CD45RO(-) (naive) T cells were cultured with Th0-, Th1-, Th2- and Th17-related cytokines and antibodies, and their mRNA was studied by real-time polymerase chain reaction (PCR). When naive CD4(+) T cells were cultured with Th1- and Th17-related cytokines, interferon (IFN)-γ mRNA and interleukin (IL)-17 mRNA were up-regulated, respectively, in BD patients. Naive CD4(+) T cells cultured in a Th17 cell-inducing condition expressed IL-23 receptor (IL-23R) mRNA excessively. IL-17 mRNA expression was induced only when naive CD4(+) T cells were cultured in the presence of IL-23. CD4(+) T cells cultured with Th17 cytokines expressed excessive RAR-related orphan receptor C (RORC) mRNA. Using intracellular cytokine staining, we found that CD45RO(+) (memory) CD4(+) T cells producing IL-17 and IFN-γ simultaneously were increased significantly. Memory CD4(+) T cells producing IFN-γ but not IL-17 decreased profoundly in BD patients. CD4(+) T cells producing IL-17 and IFN-γ simultaneously were found in BD skin lesions. Collectively, we found excessive CD4(+) T cells producing IL-17 and IFN-γ (Th1/Th17) cells in patients with BD, and possible involvement of IL-23/IL-23R pathway for the appearance of excessive Th1/Th17 cells.

Skewed TGFß/Smad signalling pathway in T cells in patients with Behçet's disease.

OBJECTIVES: Behçet's disease (BD) is a multi-systemic inflammatory disease, characterised by recurrent oral aphthosis, genital ulcers, skin lesions and uveitis. We have reported excessive Th1 cell activity in patients with BD. More recently, Th17 cells were suggested to associate with several autoimmune diseases. This study was designed to investigate the role of Th17 related cytokines and signalling molecules in patients with BD. METHODS: We examined mRNA expressions of Th1 and Th17 related cytokines and related signalling molecules in PBMC of 12 patients with BD and 14 normal controls (NC) using quantitative RT-PCR. We studied expressions of the Th17 related cytokines in other four BD patients' skin lesions by immunofluorescence. RESULTS: Major Th17 related cytokines were not detected in unstimulated PBMC in patients with BD. After stimulation, mRNA expressions of TGFß receptor type 1, IL-12 receptor ß2 and suppressor of cytokine signalling protein (SOCS) 1 on PBMC were significantly enhanced in patients with BD, as compared with NC (p<0.05). mRNA expression of RORC, a key transcription factor for Th17 cell differentiation, was comparable between BD and NC. CD4+ T cells infiltrating into BD skin lesion expressed TGFß1 much more than those infiltrating into non-Behçet's disease erythema nodosum. CONCLUSIONS: These findings suggest that TGFß/Smad signalling pathway of T cells is overactive in patients with BD.

Heterogenous graft rejection pathways in class I major histocompatibility complex-disparate combinations and their differential susceptibility to immunomodulation induced by intravenous presensitization with relevant alloantigens.

The present study investigates the heterogeneity of graft rejection pathways in class I major histocompatibility complex (MHC)-disparate combinations and the susceptibility of each pathway to immunomodulation induced by intravenous presensitization with alloantigens. Depletion of CD8+ T cells was induced by repeated administration of anti-CD8 monoclonal antibody. CD8+ T cell-depleted mice failed to generate anti-allo class I MHC cytotoxic T cell (CTL) responses but exhibited anti-allo class I MHC T cell responses, such as mixed lymphocyte reaction (MLR)/IL-2 production, that were induced by CD4+ T cells. In contrast, donor-specific intravenous presensitization (DSP), as a model of donor-specific transfusion, induced almost complete elimination of CD4+ and CD8+ T cell-mediated MLR/IL-2 production, whereas this regimen did not affect the generation of CTL responses induced by DSP-resistant elements (CD8+ CTL precursors and CD4+ CTL helpers). Prolongation of skin graft survival was not induced by either of the above two regimens alone, but by the combination of these. Prolonged graft survival was obtained irrespective of whether the administration of anti-CD8 antibody capable of eliminating CTL was started before or after DSP. The combination of DSP with injection of anti-CD4 antibody also effectively prolonged graft survival. However, this was the case only when the injection of antibody was started before DSP, because such antibody administration was capable of inhibiting the generation of CTL responses by eliminating DSP-resistant CD4+ CTL helpers. These results indicate that (a) the graft rejection in class I-disparate combinations is induced by CD8+ CTL-involved and -independent pathways that are resistant and susceptible to DSP, respectively; (b) DSP contributes to, but is not sufficient for, the prolongation of graft survival; and (c) the suppression of graft rejection requires an additional treatment for reducing DSP-resistant CTL responses. The results are discussed in the context of potential clinical application in attempts to inhibit the generation of DSP-resistant CTL responses upon the prospective DSP.

Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4.

This report shows that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a key role in T cell-mediated dominant immunologic self-tolerance. In vivo blockade of CTLA-4 for a limited period in normal mice leads to spontaneous development of chronic organ-specific autoimmune diseases, which are immunopathologically similar to human counterparts. In normal naive mice, CTLA-4 is constitutively expressed on CD25(+)CD4(+) T cells, which constitute 5-10% of peripheral CD4(+) T cells. When the CD25(+)CD4(+) T cells are stimulated via the T cell receptor in vitro, they potently suppress antigen-specific and polyclonal activation and proliferation of other T cells, including CTLA-4-deficient T cells, and blockade of CTLA-4 abrogates the suppression. CD28-deficient CD25(+)CD4(+) T cells can also suppress normal T cells, indicating that CD28 is dispensable for activation of the regulatory T cells. Thus, the CD25(+)CD4(+) regulatory T cell population engaged in dominant self-tolerance may require CTLA-4 but not CD28 as a costimulatory molecule for its functional activation. Furthermore, interference with this role of CTLA-4 suffices to elicit autoimmune disease in otherwise normal animals, presumably through affecting CD25(+)CD4(+) T cell-mediated control of self-reactive T cells. This unique function of CTLA-4 could be exploited to potentiate T cell-mediated immunoregulation, and thereby to induce immunologic tolerance or to control autoimmunity.

Chondroprotective effect of the bioactive peptide prolyl-hydroxyproline in mouse articular cartilage in vitro and in vivo.

OBJECTIVE: To investigate the direct effect of prolyl-hydroxyproline (Pro-Hyp) on chondrocytes under in vivo and in vitro conditions in an attempt to identify Pro-Hyp as the bioactive peptide in collagen hydrolysate (CH). METHODS: The in vivo effects of CH and Pro-Hyp intake on articular cartilage were studied by microscopic examination of sections of dissected articular cartilage from treated C57BL/6J mice. In this study, mice that were fed diets containing excess phosphorus were used as an in vivo model. This mouse line showed loss of chondrocytes and reduced thickness of articular cartilage, with abnormality of the subchondral bone. The in vitro effects of CH, Pro-Hyp, amino acids and other peptides on proliferation, differentiation, glycosaminoglycan content and mineralization of chondrocytes were determined by MTT activity and staining with alkaline phosphatase, alcian blue and alizarin red. Expression of chondrogenesis-specific genes in ATDC5 cells was determined by semiquantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). RESULTS: In vivo, CH and Pro-Hyp inhibited the loss of chondrocytes and thinning of the articular cartilage layer caused by phosphorus-induced degradation. In the in vitro study, CH and Pro-Hyp did not affect chondrocyte proliferation but inhibited their differentiation into mineralized chondrocytes. A combination of amino acids such as proline, hydroxyproline and prolyl-hydroxyprolyl-glycine did not affect chondrocyte proliferation or differentiation. Moreover, CH and Pro-Hyp caused two and threefold increases, respectively, in the staining area of glycosaminoglycan in the extracellular matrix of ATDC5 cells. RT-PCR indicated that Pro-Hyp increased the aggrecan mRNA level approximately twofold and decreased the Runx1 and osteocalcin mRNA levels by two-thirds and one-tenth, respectively. CONCLUSION: Pro-Hyp is the first bioactive edible peptide derived from CH to be shown to affect chondrocyte differentiation under pathological conditions.

Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells.

We report here that all trans-retinoic acid (RA), a classical morphogen, induces apoptosis during the neural differentiation of the embryonic stem cell line P19. The apoptotic cells showed, in addition to DNA cleavage, typical morphological changes including chromatin condensation, nuclear fragmentation, and cytoplasmic vacuolation. These apoptotic changes became obvious by 12 h after the addition of RA. The endogenous expression of bcl-2 in surviving cells was down-regulated during this process, and the compelled expression of bcl-2 by retroviral vectors reduced the number of apoptotic cells. Apoptosis was partially inhibited by adding antisense oligonucleotides against RA receptors (RARs) simultaneously or by transfecting a plasmid vector flanked with a RA-responsive element. Antisense oligonucleotides against retinoid X receptors (RXRs), the receptors for 9 cis-RA, did not inhibit apoptosis induced by all trans-RA. Cycloheximide and actinomycin D, inhibitors of protein and RNA syntheses, respectively, suppressed apoptosis. No changes were seen in the expression of tumor necrosis factors, their receptors, Fas, FasL, p53, or c-myc, molecules which have been suggested to participate in the apoptotic process. Addition of neurotrophins to the culture medium did not affect apoptosis. These findings suggest that the signals themselves, promote expression of molecules essential for apoptosis. Furthermore, we observed that RA induced apoptosis of cerebral neurons from murine embryos in primary culture, which suggests that RA might participate in cell death which occurs during neural development.

Comparison of the diagnosis of intervertebral disc herniation in dogs by CT before and after contrast enhancement of the subarachnoid space.

Eleven miniature dachshunds with a herniated intervertebral disc were examined by CT, first before and then after contrast enhancement of the subarachnoid space. The images were classified into three grades by three veterinarians. In four cases, lesions observed on the scans obtained after contrast enhancement had not been observed on the preliminary scans and in one case a lesion observed on the preliminary scan was not observed on the scan obtained after contrast enhancement. Hemilaminectomies were performed on the basis of the enhanced CT results, and a clinical improvement was observed in each of the dogs. Calcification was detected in all the samples of herniated intervertebral disc material.

Clinical experience of using multidetector-row CT for the diagnosis of disorders in cattle.

To determine the clinical usefulness of multidetector-row CT for the diagnosis of disorders in cattle, images were obtained from 27 cattle, which were then subjected to postmortem and histopathological examinations. The cattle were divided into three categories of disorder: neurological (18 cases), skeletal (four cases) and other (five cases). In five cattle, which were suspected to have brain diseases, no abnormalities were identified by either CT or histopathological examination. Eight types of lesions were detected by CT in the cattle with neurological and vestibular disorders. The diseases diagnosed included hydrocephalus (three cases), intracranial arachnoid cysts (three cases), otitis media (five cases), cerebral abscess (one case), meningoencephalocele (one case), porencephaly (one case), bicephalus (one case) and rupture of the spinal cord (one case). Lesions were identified in all the cattle with skeletal disorders, including luxation (two cases), fracture (two cases), spondylosis (one case) and congenital disorders of the skeletal system (one case). Morphological disorders in the eyes (one case), nasal cavity (two cases), frontal sinuses (one case), thyroid glands (two cases), lung fields (two cases) and abdominal organs (two cases) were diagnosed by CT.

Hyperkalemia in familial mitochondrial cytopathy.

AIM: To contribute to understanding the pathogenesis of hyperkalemia that often occurs in patients with diabetes. MATERIALS AND METHODS: We describe 3 familial cases of mitochondrial diabetes mellitus. The mitochondrial A3243G point mutation was confirmed in a mother and her 2 children. We examined their clinical features and pathological findings, and assessed heteroplasmy of mutant mitochondria DNA (mtDNA) by molecular analysis. RESULTS: The second son had spontaneous hyperkalemia and hyporeninemic hypoaldosteronism. Histopathological examination revealed severe tubulointerstitial and vascular changes around the juxtaglomerular apparatus. The mother only showed intermittent hyperkalemia concurrently with the aggravation of heart failure, and the pathological changes in her kidneys were mild. Heteroplasmy was more severe in the second son than in the mother. CONCLUSION: Heteroplasmy of mitochondrial cytopathy combined with diabetes mellitus led to abnormalities resembling those seen in Type IV renal tubular acidosis.

Nodular fasciitis involving the palm.

Nodular fasciitis (NF) is a self-limiting fibrous neoplasm that can be mistaken for a soft tissue sarcoma. It is characterised by rapid growth, slight pain and local tenderness. Although it is frequently found in the forearm, a lesion distal to the wrist is quite rare. We present two unusual cases of NF involving the palm, supported by detecting ubiquitin specific protease 6 gene rearrangement. The first patient had non-intraneural NF presenting as peripheral neuropathy affecting the digital nerve while the second patient suffered from painless, non-tender NF in the palm, which had not regressed spontaneously during the five months prior to surgery.

Vascularised fibular grafts for reconstruction of extremity bone defects after resection of bone and soft-tissue tumours : a single institutional study of 49 patients.

AIMS: The aims of this study were to analyse the long-term outcome of vascularised fibular graft (VFG) reconstruction after tumour resection and to evaluate the usefulness of the method. PATIENTS AND METHODS: We retrospectively reviewed 49 patients who had undergone resection of a sarcoma and reconstruction using a VFG between 1988 and 2015. Their mean follow-up was 98 months (5 to 317). Reconstruction was with an osteochondral graft (n = 13), intercalary graft (n = 12), inlay graft (n = 4), or resection arthrodesis (n = 20). We analysed the oncological and functional outcome, and the rate of bony union and complications. RESULTS: Five- and ten-year overall survival rates were 89% and 86%, respectively. Local recurrence occurred in two patients. Eight patients developed pulmonary metastases. Bone union was achieved in 44 patients (90%). Fracture occurred in six patients (12%), infection in three (6%), and nonunion in five (10%). The mean Musculoskeletal Tumor Society (MSTS) scores were as follows: osteochondral graft 70%; intercalary graft 73%; inlay graft 89%; and resection arthrodesis 83%. CONCLUSION: Although associated with a relatively high rate of complications, each reconstruction method is useful, with a high rate of successful limb salvage and a good long-term functional outcome. Cite this article: Bone Joint J 2017;99-B:1237-43.

Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody.

Immune regulation has been shown to be involved in the progressive growth of some murine tumors. In this study, we demonstrated that a single in vivo administration of an amount less than 0.125 mg of anti-CD25 interleukin 2 receptor alpha monoclonal antibody (mAb; PC61) caused the regression of tumors that grew progressively in syngeneic mice. The tumors used were five leukemias, a myeloma, and two sarcomas derived from four different inbred mouse strains. Anti-CD25 mAb (PC61) showed an effect in six of the eight tumors. Administration of anti-CD25 mAb (PC61) caused a reduction in the number of CD4+ CD25+ cells in the peripheral lymphoid tissues. The findings suggested that CD4+ CD25+ immunoregulatory cells were involved in the growth of those tumors. Kinetic analysis showed that the administration of anti-CD25 mAb (PC61) later than day 2 after tumor inoculation caused no tumor regression, irrespective of depletion of CD4+ CD25+ immunoregulatory cells. Two leukemias, on which the PC61-treatment had no effect, seemed to be incapable of eliciting effective rejection responses in the recipient mice because of low or no antigenicity.

Cytosolic and mitochondrial phosphoenolpyruvate carboxykinase of the bullfrog, Rana catesbeiana, liver.

The mitochondrial and cytosolic phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase(transphosphorylating), EC 4.1.1.32) occurring in the bullfrog (Rana catesbeiana) liver were studied. The enzymes in th two intracellular compartments of both tadpole and adult frog liver were immunologically identical. Both radioactively-labelled forms of the mitochondrial and cytosolic phosphoenolpyruvate carboxykinase from bullfrog liver were imported at the same rate into intact mitochondria in vitro. The mitochondrial and cytosolic enzyme activities did not respond to the administration of glucagon, glucocorticoid, quinolinate and D-mannoheptulose which are known as enhancers of phosphoenolpyruvate carboxykinase, but were found to increase during natural metamorphosis. The former activity was markedly increased in the tadpoles treated with 3,5,3'-triiodothyronine. It was supposed that in the bullfrog liver the phosphoenolpyruvate carboxykinase localized in the mitochondria is of central importance in phosphoenolpyruvate synthesis from oxaloacetate.

An exploration of the binding site of aldolase using alkanediol monoglycolate bisphosphoric esters.

Alkanediol monoglycolate bisphosphoric esters (P-O-CH2-CO-O-(CH2)n-O-P), which are analogues of the aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) substrate fructose 1,6-bisphosphate, were synthesized and used for probing its active site. The Ki value was lowest when the maximum distance between the phosphorus atoms of the bisphosphate was brought close to that of fructose 1,6-bisphosphate. The binding constants estimated from difference spectra correlate well with Ki values for the substrate analogues. Propanediol monoglycolate bisphosphoric ester protected aldolase from inactivation by 1,2-cyclohexanedione, which preferentially attacks arginine-55. However, propanol phosphate had little protective effect. The synthesized phosphate compounds protected the enzyme against inactivation by trypsin, and also against spontaneous denaturation. These results suggest that the synthesized phosphate compounds bind to aldolase at the active site, which tends to keep the distance constant between the two phosphate-binding sites for the open-chain form of fructose 1,6-bisphosphate, and stabilize the natural conformation of the enzyme. Both arginine-55 and lysine-146 are shown to participate in the phosphate-binding site for the C-1-phosphate of fructose 1,6-bisphosphate.

Effects of dietary docosahexaenoic acid on surface molecules involved in T cell proliferation.

It is known that n-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) suppress immunity as compared with n-6 PUFA such as linoleic acid (LA), but the mechanism involved in this phenomenon is still unclear. The present study was designed to assess the effect of dietary DHA on the surface molecules involved in T cell proliferation. Weanling male C57BL/6 mice were divided into four dietary groups that were fed a 10% fat diet for 4 weeks varying in amounts of DHA and LA. As the dietary DHA concentration increased, the surface expression of CD4 and CD8 on splenic T cells decreased, while that of CD28 increased. The surface expression of CD3, however, was invariable in all dietary groups. DNA synthesis of splenic T cells, induced by CD3 crosslinkage with anti-CD3 epsilon monoclonal antibody in the presence of CD28-mediated costimulation, increased as the DHA concentration was elevated. These observations suggest that diets rich in DHA exert some of their immunomodulatory effects by a downregulation of surface expression of CD4 and CD8 and by an upregulation of CD28-mediated costimulatory signal.