A vaccine that is safe in a naive recipient may have negative effects in one with pre-existing immunologic memory (Doherty, 2005). Table 1

shows several tuberculosis vaccine candidates that are currently in advanced stages of clinical trials. Of these, subunit tuberculosis vaccines have received special attention because, in spite of their poor immunogenicity, Estrogen antagonist they exhibit a high degree of safety and their production can be standardized. Currently, such tuberculosis subunit vaccines are prepared from recombinant proteins, purified from bacterial expression vectors or formulated as naked DNA, consisting of recombinant plasmids encoding Mtb antigens under the control of eukaryotic promoters (Doherty & Andersen, 2005; Hoft, 2008; Carstens, 2009). They can stimulate T-cell responses against key subunit antigens and are

safe even in immunosuppressed individuals. Their main drawback is the limited availability of adjuvants approved for human use to boost their immunogenicity (Hogarth et al., 2003; Mills, 2009). Box 1 provides a short description of adjuvants Alvelestat solubility dmso for human use that have been the result of many years of research and development, including oils and aluminium adjuvants, synthetic adjuvants, second-generation delivery-depot systems and receptor-associated adjuvants (Ott & Van Nest, 2007). Many of these adjuvants have been tested for their efficacy in tuberculosis vaccines, mostly in mouse models in combination with different antigens or fusion proteins. When used alone or in conjunction with BCG in a ‘prime-boost’ strategy or coadjuvanted with cytokines or other molecules, many of these vaccines have been shown to confer Baricitinib protective immunity (Lindblad et al., 1997). Secreted proteins, HSP, lipoproteins and putative phosphate transport receptors (PstS)

have all been evaluated for subcutaneous, oral or intranasal priming vaccination, followed by intradermal or oral BCG vaccination (Doherty et al., 2002; Hogarth et al., 2003; Hoft, 2008). Likewise, emulsions (Haile et al., 2004, 2005), microspheres (Ajdary et al., 2007), toxin derivatives (Takahashi et al., 2006; Badell et al., 2009), cationic lipids (D’Souza et al., 2002) and oligodeoxynucleotides (Kamath et al., 2008) have demonstrated efficacy in inducing strong T-cell responses with high titres of IFN-γ and specific antibodies. Table 2 summarizes several studies evaluating the efficacy of different antigen/adjuvant combinations for tuberculosis vaccination.

Recognition of flagellin by NLRC4 is likely indirect and mediated through host cellular factors, which trigger inflammasome activation since there is no evidence to date for a direct interaction between NLRC4 and flagellin. NLRC4 RAD001 concentration can sense additional molecules besides flagellin as certain aflagellated bacteria including S. flexneri14 and Mycobacterium tuberculosis21 activate caspase-1 via NLRC4. The NLR protein Naip5 is also critical for the sensing

of a conserved C-terminal portion of flagellin from L. pneumophila and for NLRC4-dependent caspase-1 activation 22. Remarkably, Naip5 is not required for caspase-1 activation triggers by S. typhimurium or P. aeruginosa infection 22. The mechanism by which Naip5 regulates the NLRC4 inflammasome activated by L. pneumophila remains

unclear 23. Because caspase-1 is critical for restricting the replication of L. pneumophila in the host cytosol, these studies suggest that both Naip5 and NLRC4 control the susceptibility to L. pneumophila through the sensing of flagellin and caspase-1 activation. Alternatively, Naip5 may have additional NLRC4-independent roles check details that are important in restricting the growth of L. pneumophila in macrophages. Recent studies suggest that caspase-7 which is activated by the NLRC4 inflammasome is an important factor in restricting L. pneumophila replication, although the mechanism involved remains elusive Oxalosuccinic acid 24. While the NLRC4 inflammasome

is activated primarily by cytosolic flagellin, a plethora of microbial and non-microbial stimuli have been reported to activate caspase-1 via NLRP3. These include multiple TLR agonists and the Nod2 agonist, MDP 25, 26. In addition, large particles including urate crystals, silica, asbestos, β-amyloid and aluminum hydroxide activate the NLRP3 inflammasome in phagocytes pre-stimulated with microbial ligands such as LPS 6. Unlike TLR ligands, these particulate and crystalline molecules can activate the inflammasome in the absence of extracellular ATP 6. Although the critical cellular events remain poorly understood, disruption of the lysosomal membrane and/or production of ROS 27 have been suggested to be important for particulate matter-induced NLRP3 activation 28. The ability of multiple pathogen-associated molecular patterns to activate the NLRP3 inflammasome is puzzling because most of the molecules including TLR ligands are structurally unrelated. Recent findings suggest that most or all TLR agonists as well as MDP do not activate the NLRP3 inflammasome directly. Instead, they prime the inflammasome via NF-κB to promote caspase-1 activation 29, 30, which is consistent with previous results 31. Consistently, TNF-α and IL-1 are as effective as TLR agonists in promoting caspase-1 activation in response to ATP or silica 29.

Other than NLRP3, NLRP1 is the only inflammasome NLR protein reported in the context of EAE for its Panobinostat mw intra-axonal accumulation,[47] but involvement of the NLRP1 inflammasome in EAE is not yet known. A major function of the NLRP3 inflammasome is the maturation and secretion of IL-1β and IL-18. It is known that IL-1β plays a role in demyelination,[48] breakdown of blood–brain barrier (BBB),[48, 49] microglia activation[49] and promotion of IL-17 expression both by CD4+ T and γδT cells.[50, 51]

The outcome from these responses is the enhancement of EAE progression. Interleukin-18 is also known to promote IL-17 production by CD4 T+ cells, as well as γδT cells,[52] and exacerbates demyelination.[42] Attenuated Th17 (and Th1) responses were originally considered to be a major underlying mechanism for the resistance of NLRP3 inflammasome-deficient mice against EAE.[41,

52] However, it now appears that the lack of the NLRP3 inflammasome (in APCs) disables T helper cells and APCs in migrating to the CNS. This Kinase Inhibitor Library inability to migrate cells to the CNS is a major cause of resistance against EAE in Asc−/− and Nlrp3−/− mice.[43] Interestingly, T cells primed by NLRP3 inflammasome-deficient APCs do not migrate into the CNS, but are encephalitogenic, only lacking chemotactic ability.[43] Therefore, when directly transferred into the CNS, transfer of T cells primed by NLRP3 inflammasome-deficient APCs is able to induce EAE.[43] This result strongly suggests that cell migration 3-oxoacyl-(acyl-carrier-protein) reductase is one of the most critical factors for the NLRP3 inflammasome in exerting an effect on EAE progression. The cell migration mechanism was explained with IL-1β and

IL-18, which are processed by the NLRP3 inflammasome and up-regulate expression of chemokines and their receptors both in T helper cells and APCs. Total T helper cells (as well as Th17 and Th1 cells) from immunized Asc−/− and Nlrp3−/− mice express low levels of CCR2, CXCR6 and osteopontin, which are critical to MS and EAE progression.[53-62] Without the NLRP3 inflammasome, APCs also reduce expression of chemokines and their receptors, such as CCL7/MCP3 (CCR2 ligand), CCL8/MCP2 (CCR2 ligand), CXCL16 (CXCR6 ligand) and α4β1 integrin (osteopontin receptor).[43] The NLRP3 inflammasome induces expression of molecules that enhance cell migration by providing IL-1β and IL-18. Intriguingly, those molecules are matching pairs of chemokines and their receptors between T cells and APCs (Fig. 1). Type 1 interferons (IFN-I), such as IFN-α and IFN-β, are involved in various aspects of immune responses. IFN-β has been used for more than 15 years as a first-line treatment for MS, and also markedly attenuates EAE development. Previous studies have shown that IFN-β suppresses the production of IL-1β through reduction of pro-IL-1β via the autocrine effect of IL-10.

Thereafter the posterior thighs APO866 purchase were dissected from medial to lateral, distinguishing the perforators at the level of the superficial fascia. The perforators were localized and origin, source, length and diameter of the perforators were documented. Analysis occurred using ANOVA and the two proportion Z test. The distribution of musculocutaneous and septocutaneous perforators was respectively 69.1% and 30.9% (P = 0.002). The PTR was divided in thirds. Most perforators (53.2%) were found in de middle third of the PTR. The deep femoral artery (DFA) was the main origin of perforators (61.7%), followed by the superficial femoral artery (SFA) (27.7%) and the popliteal

artery (PA) (10.6%). The DFA Veliparib nmr perforators were the longest with a mean length of 13.7 ± 4,69 cm, the SFA perforators were 9.79 ± 3.76 cm and the PA perforators were 8.6 ± 3.37 cm. The PTR offers a sufficient number of suitable perforators to serve as an adequate donorsite for pedicled and free flaps. © 2013 Wiley Periodicals, Inc. Microsurgery 33:376–382, 2013. “
“Defects of the Achilles tendon and the overlying soft tissue are challenging to reconstruct. The lateral-arm flap has our preference in this region as it provides thin pliable skin, in addition, the fascia and tendon can be included in the flap

as well. The aim of this report is to share the experience the authors gained with this type of reconstruction. The authors report the largest series in the published reports today. Patients and methods: A retrospective review was performed of all patients treated between January 2000 and January 2009 with a lateral-arm flap for a soft-tissue defect overlying the Achilles tendon. Results: In the reviewed period, 16 soft-tissue defects overlying the Achilles tendon were reconstructed, with a mean follow-up of 63 months. In three cases, tendon was included into the flap and in two, a sensory nerve was coapted. Fifteen cases (94%) were successful, one failed. In seven cases, a secondary procedure Orotic acid was necessary for thinning of the flap. Conclusion: The lateral-arm flap

is a good and safe option for the reconstruction of defects overlying the Achilles tendon. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012. “
“Severe injuries at foot and ankle level with loss of soft tissues and bone are often treated by means of amputation. The transfer of composite free flaps from various donor sites may provide anatomical reconstruction of the foot and ankle and function. Ten patients who sustained severe combined tissue injuries of the foot requiring reconstruction with composite free flaps were studied with a mean follow-up of 3.4 years. A thorough clinical examination was performed, and gait analysis was carried out with kinetic and kinematic parameters. Bone integration and healing was observed with satisfactory foot morphology.

Immature MoDCs were incubated in PIC-A549 CM or PIC-DU CM for different times and STAT1 phosphorylation was analyzed by Western blotting (Fig. 2A). To rule out the possibility of activation of STAT1 by residual amounts of poly I:C present in PIC-A549 CM, all CMs were treated, before addition to MoDCs, with soluble human recombinant TLR3 that neutralizes the poly I:C activity [25]. As control, MoDCs were stimulated with only

poly I:C. Interestingly, STAT1 phosphorylation was detected neither in MoDC incubated with fresh media nor in nonstimulated A549 or DU145 supernatants (A549 and DU-CM, respectively) (Fig. 2A). In contrast, MoDC incubated with PIC-A549 and PIC-DU CM showed strong STAT1 phosphorylation as early as

15 min post addition of the CM. Stimulation of MoDCs with poly Y-27632 chemical structure I:C alone did not induce STAT1 phosphorylation at the time periods assayed. Similarly, only murine BMDCs cultured with PAU-B16 CM showed STAT1 phosphorylation after 30 min of incubation LDK378 datasheet (Supporting Information Fig. 1A). Given that IFN-β-induced STAT1 phosphorylation is responsible for the CXCL10 production by DCs [12], we also evaluated whether PIC-A549 CM was capable of inducing CXCL10 mRNA expression in MoDCs. As expected, a strong induction of CXCL10 mRNA expression was detected only in Mo-CD incubated with PIC-A549 CM (Fig. 2B). These results suggest that MoDCs can be targets of IFN-β present in PIC-A549 or PIC-DU145 CM. Tumor-derived factors significantly inhibit the generation as well as the maturation of DCs [22, 23]. Since type I IFNs and pro-inflammatory cytokines are positive modulators of both phenomena, we hypothesized Bacterial neuraminidase that IFN-β present in PIC-A549 CM or PIC-DU CM could act as a positive modulator of DC maturation and participate in reversing this inhibited state. To

address this hypothesis, MoDCs were first incubated with A549-CM or PIC-A549 CM for 48 h and classical activation markers of DC maturation (CD86 and CD40) were evaluated (Fig. 3). The same experiment was performed using DU-CM and PIC-DU CM. The results obtained using both cell lines were similar: interestingly, PIC-A549 CM and PIC-DU CM are capable per se of significantly enhancing the expression of CD86 and CD40 markers (Fig. 3A and B). When MoDCs were matured with LPS in the presence of A549-CM or DU-CM, the increment of CD86 expression showed a significant drop compared to the increment observed when MoDCs were matured with LPS alone. This inhibitory effect of A549-CM or DU-CM on MoDC maturation was abolished when the CM was originated from PIC-A549 CM or PIC-DU CM. Similar results were observed when a different maturing stimulus, such as the TLR7/8 ligand, R848, was used (Supporting Information Fig. 2A and B).

Recently, antibodies to myelin oligodendrocyte

glycoprotein (MOG) have been identified in a subset of patients with seronegative NMOSD [194-197]; the pathogenic, prognostic selleck and therapeutic relevance of these antibodies is currently being investigated. Moreover, anti-CV2/CRMP5 and, possibly, NMDA receptor autoimmunity have been shown to mimic NMO in single patients [198, 199]. In addition, connective tissue disorders (CTD), in particular systemic lupus erythematosus and Sjögren’s syndrome, have been implicated in the pathogenesis of NMOSD in some patients [64, 65, 67]. A broad summary of the differential diagnosis of NMO is provided in the reference list [200-202]. It should be kept in mind that a lack of NMO-IgG/AQP4-antibody seropositivity does not rule out a diagnosis of NMO, according to the currently most widely adopted

diagnostic criteria [84]. As will be discussed in the following sections, CSF analysis and spinal cord and brain imaging can facilitate the differential diagnosis of seronegative NMO and MS. CSF findings in NMO and MS differ markedly. CSF-restricted oligoclonal bands (OCB), a diagnostic mainstay in MS, are present in only approximately 18% of AQP4-antibody-positive cases and frequently disappear during remission [1, 165]. Similarly, quantitative evidence for intrathecal IgG synthesis, i.e. an elevated IgG CSF/serum ratio, is only present in approximately 8% of CSF samples and exclusively during relapse [165]. By contrast, OCB www.selleckchem.com/products/ITF2357(Givinostat).html are present in far more than 90% of cases in classical MS [203, 204] and can be detected over the entire course of the disease [205]. A positive, polyspecific, intrathecal immune reaction to measles, rubella and varicella zoster virus (also termed MRZ reaction Aspartate [206-208]) – as defined by at least two out of three positive antibody indices – is present in 60–80% of MS patients, but absent in approximately 97% of NMO patients [1, 209].

CSF white cell counts (WCC) are often normal or only mildly elevated in NMO (median 19/μl during acute disease, 3/μl during remission [165]). However, cell counts >100/μl are possible [1, 165], especially during relapse [165]. In addition to lymphocytes and monocytes, cytology often reveals neutrophilic and eosinophilic granulocytes [1, 36, 165], cell types which are usually absent in MS. An elevated albumin CSF/serum ratio, indicating blood–CSF barrier (BCB) disruption, and an increase in total protein is present in approximately 50% of cases, more often during acute attacks. CSF lactate levels are elevated during acute myelitis in approximately 40%, but normal during remission [165, 210].

The secretion of cytokines after PBMC challenge was related to the number of months that the patient had experienced symptoms before performing the PBCM challenge. There were significant relationships between the IL-12 secretion induced LY2835219 by P-glucan, chitin and LPS (correlation coefficient 0·783, P < 0·001, 0·656, P = 0·002 and 0·835, P < 0·001, respectively) but not for S-glucan. There was also a relation between the duration of the symptoms and the spontaneous secretion of TNF-α (0·323, P = 0·015) and the LPS-induced secretion of TNF-α (0·490, P =0·020). The relationship between duration of symptoms and the P-glucan-induced

secretion of IL-12 is illustrated in Fig. 1. The serum values of cytokines were higher among subjects with sarcoidosis (data not shown) with significant differences for IL-6 and IL-12 (P < 0·001 and 0·003, respectively). The significant relationships between the in vitro production of cytokines and serum levels of IL-2R and IL-12 in the whole material are reported in Table 3. The serum level of IL-12 was related consistently to the secretion of different cytokines induced

by P-glucan. The relationship to IL-2R was less marked. There was also a relation between the P-glucan-stimulated release of IL-12 and the serum level of TNF-α. There were no significant relationships for Selleck Poziotinib the chitin-induced secretions and serum cytokines. The average level of NAHA in the homes of controls was 12·9 (1·5) U/m3 and among subjects with sarcoidosis 30·9 (6·1) (P = 0·046). Among controls there were no relations between NAHA levels at home and the in vitro secretion of different cytokines. In subjects with sarcoidosis there were significant relationships between NAHA levels and the spontaneous secretion of IL-6, IL-10 and IL-12 (correlation coefficient 0·507, P = 0·027, correlation coefficient 0·725, P < 0·001 and correlation coefficient 0·567, P = 0·011, respectively). There was also an inverse relationship between the chitin-induced secretion of IL-12 and the NAHA levels in the homes and between NAHA and the LPS induced secretion of IL-6 and IL-10 (correlation

coefficient 0·621, P = 0·005 and correlation coefficient 0·457, P = 0·049, respectively). Figure 2 illustrates Farnesyltransferase the relation between the amount of NAHA in the homes of subjects with sarcoidosis and the spontaneous secretion of IL-12. Subjects with a high fungal exposure at home also had a higher spontaneous secretion of IL-12 from their PBMC. The relations between chest X-ray scores and the secretion of all cytokines after stimulation with P-glucan and LPS for the whole material are shown in Table 4. There were significant relationships between chest X-ray scores and the secretion of all cytokines after stimulation with LPS or P-glucan. The major findings from the study stem from the relation between reactions induced by FCWA in vitro, in vivo and the environment.

aeruginosa–S. aureus NVP-LDE225 purchase co-culture biofilms, we used the P. aeruginosa pilH mutant in our study. The P. aeruginosa pilH in-frame deletion

mutant showed an increased level of surface piliation and slightly reduced twitching zones in an agar stab plate assay (Barken et al., 2008). In co-culture biofilms, the size of the P. aeruginosa pilH–S. aureus MN8 mixed-species microcolonies was increased compared with the size of the P. aeruginosa PAO1–S. aureus MN8 mixed-species microcolonies (Fig. 3c). These results suggest that the level of P. aeruginosa surface piliation has an important impact on microcolony formation in the P. aeruginosa–S. aureus co-culture biofilms. Previous reports have shown that P. aeruginosa type IV pili are able to bind DNA, which is a key component of the biofilm EPS (Whitchurch et al., 2002; van Schaik et al., 2005). We stained the P. aeruginosa–S. aureus co-culture biofilms

with Live/Dead viability stain and observed populations of dead cells accumulated inside the mixed-species microcolonies in the P. aeruginosa PAO1–S. aureus MN8 biofilm (Fig. 4a and b). We observed the same pattern of localization FK866 of dead cells in the P. aeruginosa pqsA–S. aureus MN8 co-culture biofilms (Fig. 4c and d). These results indicate that S. aureus dead cells might be a major source of eDNA of co-culture biofilms, because the pqs gene operon was shown to be required for eDNA release of P. aeruginosa biofilms (Allesen-Holm et al., 2006; Yang et al., 2007). We then grew co-culture biofilms of P. aeruginosa PAO1 and an S. aureus atl mutant (Toledo-Arana et al., 2005) defective in producing a major autolysin of S. aureus. We observed the same pattern of mixed-species microcolony formation in P. aeruginosa PAO1–S. aureus atl co-culture biofilms U0126 as in the other P. aeruginosa PAO1–S. aureus co-culture biofilms (Fig. S2). This indicated that the dead cells we observed from the mixed-species microcolony structures of co-culture biofilms were not

due to the activity of atl autolysin of S. aureus. To test the hypothesis that eDNA is involved in the type IV pili-mediated interactions in P. aeruginosa–S. aureus co-culture biofilms, we challenged the P. aeruginosa–S. aureus co-culture biofilms with low concentrations of bovine DNase I. When DNase was added to the medium, the P. aeruginosa PAO1–S. aureus MN8 co-culture biofilms showed a significant reduction in the biomass and sizes of mixed-species microcolonies (Fig. 5). Only very small and thin microcolonies were formed in P. aeruginosa PAO1–S. aureus MN8 co-culture biofilms in the presence of DNase in the biofilm medium (Fig. 5). These results suggest that type IV pili–eDNA interactions might be involved in mixed-species microcolony formation of P. aeruginosa–S. aureus co-culture biofilms. We used a D. discoideum phagocytosis model to investigate phagocytosis resistance of the monospecies biofilm and co-culture biofilms. Monospecies biofilms formed by P. aeruginosa PAO1, rpoN, S. aureus MN8 and P.

The aim of this study is to report the results of treatment using a free flap procedure followed by ipsilateral vascularized fibular transposition (IVFT) for reconstruction of composite tibial defects. Ten patients underwent a free flap procedure followed by IVFT and plating. The mean size of the flaps was 12.1 × 6 cm2. The mean length of bone defect was 5.35 cm. IVFT were performed 4.3 months following the free flap.

Patients were followed for an average of 3.4 years. All flaps survived. The average time to union of the proximal and distal ends was 5.2 and 6.7 months, respectively. There were neither stress fractures of the transferred fibula nor recurrent infections. One patient demonstrated a medial angulation of 8° in the reconstructed tibia but experienced no difficulties in activities of daily living. At the last follow-up time point, all patients were able to walk without an assist device and were satisfied with the preservation of the injured DAPT mw lower extremity. Free flap procedures followed by IVFT for the treatment of composite tibial defects may reduce complications at the recipient site and infections, such as osteomyelitis. The plating technique combined

with IVFT allowed bone union without additional operations or stress fractures in our series. We suggest that staged free flap and IVFT is useful for the treatment of composite segmental tibial defects. © 2011 Wiley-Liss, Inc. Microsurgery, 2011. “
“The three commonly used free flaps for circumferential pharyngeal reconstruction after total pharyngo-laryngectomy are the radial forearm flap (RFF), the anterolateral thigh (ALT) flap, and the jejunum Selleckchem Caspase inhibitor flap. This Phospholipase D1 study was to objectively compare three different flaps for pharyngeal reconstruction during the past 10 years. Stricture and fistula were assessed using esophagogram and esophagoscopy. Forty-five patients with pharyngeal reconstructions had esophagram and esophagoscopy

done postoperatively to assess for strictures and fistulas. These patients were divided into three groups based on pharyngeal reconstruction by ALT, RFF, and jejunal flaps. From the results of the esophagogram and esophagoscope, the presence of a fistula or stricture was compared and analyzed. There was only one ALT flap failure. The rate of fistula was 33%, 50%, and 30% in the ALT, RFF, and jejunal flap group respectively. The fistula rate revealed no significant difference between ALT, RFF, jejunal flap groups (P = 0.63). The rate of stricture was 38.1%, 57.1%, and 0% in the ALT, RFA, jejunal flap groups respectively. The stricture rate in jejunal flap group revealed significant decrease (P = 0.0093). Jejunal flap has a significantly lower rate of stricture for reconstruction of circumferential pharyngeal defects when compared with RFF or ALT flaps. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“Purpose of the article is to present the use of the scapular tip free flap (STFF) for the reconstruction of oromandibular defects.

The renal graft survival was significantly decreased in our obese transplant recipients, no matter whether it was death-censored or death-uncensored. Among obese recipients, the association with worse graft survival is likely multifactorial. Changes common in the native kidneys of obese patients may explain the deleterious effects of obesity on transplant outcomes, although this has not been validated. selleck chemicals llc Associated comorbidities such as hypertension, DM and hyperlipidaemia

may predispose obese subjects to chronic allograft nephropathy.24 Recurrence of glomerulonephritis, especially FSGS, is common in renal transplant recipients and the association between FSGS and obesity is well documented in the published work. In our study, there is a RXDX-106 solubility dmso higher incidence of recurrence of glomerulonephritis in obese patients. In addition, we demonstrated that obesity was associated with significantly lower GFR at 6 months post-transplant. In fact, our findings

are in agreement with the results of an earlier study.10 Hence, our result supports the use of a BMI cut-off value of 25 kg/m2 at the time of transplant for risk stratification in Asian renal transplant recipients. However, recent evidence showed that overweight, with a lower BMI cut-off value than obesity, is already associated with an increased risk of comorbidities in our general population.9 As a result, we re-analyzed our data using a BMI cut-off value of 23 kg/m2. In this case, we could not demonstrate any significant difference in patient and graft survival between the normal and overweight groups. However, the renal graft function was significantly better in patients within the normal group. It remains to be seen whether we should

aim at a lower BMI for our renal transplant recipients. Thiamet G There has been hypothesis that inadequate nephron dose may influence graft outcome, especially when a smaller kidney is transplanted. Kim et al. showed that KW/BW ratio is an important index for estimating the donor/recipient size mismatch, and found that recipients with a high ratio showed a better graft function.13 Brenner et al. also showed that recipients with a ratio of less than 2 g/kg are at particular risk of reduced renal graft survival.25 However, this hypothesis remains controversial. Paediatric donor kidneys have been successfully transplanted into adult recipients with favourable outcome in different centres.26 In our study, donor kidney weight was measured and KW/BW ratio was estimated. Although we found that those patients with graft failure had a lower KW/BW ratio, the difference was not statistically significant. In fact, some researchers failed to prove the nephron under-dosing effects.27 A recent study showed that higher BMI was found to be independently associated with a higher GFR and filtration fraction (FF) in renal transplant recipients.