Rather, it is possible that a

productive Seliciclib nmr infection of MPyV may be blocked at a step after the generation of viral DNA in the infected cells. Previous studies have indicated that viral proteins and particles could be produced in oligodendrocytes and other cell types in the brain tissues of MPyV-inoculated mice (15, 16). Thus, it is speculated that MPyV temporarily replicates in brain cells, such as oligodendrocytes, and progeny virions may be retained in the infected cells without being released into the extracellular spaces in the brains of BALB/c and KSN mice, thereby leading to the lack of viral spread to the adjacent cells. Further analyses, such as immunoblotting, immunohistochemistry and electron microscopy, need to be conducted to better understand the mechanism of MPyV replication in the mouse brain. Previous investigations suggested that the intracranial injection of MPyV into the cerebrum led selleckchem to demyelination of the brain stem and spinal cord, thereby

causing paralysis and wasting in adult nude mice bearing human tumors (15, 16). In the current study, KSN nude mice did not exhibit any clinical symptoms after MPyV inoculation. This discrepancy in results can be explained by the differences in the inoculation procedure. Because extremely small amounts of virus inoculum were stereotaxically microinfused into the striatum of KSN mice, it is thought that the brain stem and spinal cord were less affected or not affected by MPyV infection; however, in the preliminary

experiment, stereotaxic inoculation of MPyV into the brain stem did not lead to paralysis in KSN mice (Nakamichi K, 2010, unpublished data). Thus, a severe immunodeficient state and/or tumor products may be associated with the MPyV-mediated demyelination in nude mice following transplantation Mephenoxalone with human tumors. When examining the spatial and temporal patterns of MPyV infection in the brain, the low but significant levels of viral DNA were observed in regions away from the inoculation site in the perfused brains of KSN mice between 8 and 30 days p.i. The onsets of the increase in viral DNA in these brain areas coincided with those in the spleen, blood, and liver; thus, it is probable that MPyV may be transported from the inoculation site to other areas of the brain and peripheral organs. It is also of interest to note that detectable amounts of MPyV DNA were present in the brains not only of KSN nude mice but also of BALB/c mice even at 30 days p.i. These observations indicate that MPyV infects the brains of immunocompetent mice without being completely cleared by immune responses. The characterization of viruses retained in the brain needs to be conducted to clarify long-term MPyV infection. In conclusion, MPyV established an asymptomatic long-term infection in the mouse brain after stereotaxic inoculation into the brain tissue.

For NHD, dialysate concentrations need to be

adjusted especially increasing calcium and decreasing bicarbonate concentration, phosphate supplementation may be required and blood and dialysate flow rates can often be lowered. Treatment frequency and/or duration of HD regimens may also need to be adjusted to meet clearance targets and normalize blood pressure, extracellular fluid volume and serum parameters. The author gratefully acknowledges the expertise of Professor Peter Kerr (Monash Medical Centre, Clayton), Associate Professor John Agar (Barwon Health, Geelong) and the home haemodialysis nursing staff at Barwon Health (Geelong, Victoria) for their assistance in reviewing this manuscript. “
“The Australian and New Zealand Society AZD8055 of Nephrology gratefully acknowledges the support of the following companies: Sustaining Member/Education Partner/Research Partner Roche Products Pty Ltd Sustaining Members/Education Partners Baxter Healthcare Pty Ltd Janssen-Cilag Pty Ltd Novartis Pharmaceuticals Australia Pty Ltd Pfizer Australia Pty Ltd Sanofi Shire Australia Pty Ltd Sustaining Member/Research Partner Amgen Australia Pty Ltd Sustaining Members Romidepsin Fresenius Medical Care Australia Pty Ltd Gambro Pty Ltd Servier Laboratories Australia

Pty Ltd “
“Aim:  To determine the proportion of patients achieving tacrolimus whole-blood concentrations of ≥10 ng/mL within 3 days of kidney transplantation, after randomization either to standard dosing (control group) or post-transplantation dosing guided by a 2-hour (C2) level following a preoperative tacrolimus dose (T2 group). Methods:  The first postoperative tacrolimus dose was given either according to standard care (control group) or 0.15 mg/kg b.d. if the pre-transplant C2 level was ≤20 ng/mL, 0.1 mg/kg b.d. if the C2 level was 21–59 ng/mL or 0.05 mg/kg b.d. if the C2 level was ≥60 ng/mL (T2 group). Subsequent dosing in both groups was based upon tacrolimus trough level monitoring. Participants received concomitant mycophenolate mofetil and steroids. Results:  Ninety patients were recruited, of which 84 were included in the analysis (control group n = 43; T2 group n = 41). There was no

difference in the proportion of subjects achieving tacrolimus trough levels ≥10 ng/mL (82.9% Control vs Methamphetamine 93.0% T2; P = 0.19) or between 10 and 15 ng/mL (41.5% Control vs 41.9% T2; P = 0.97) at day 3 post transplant. The T2 group achieved tacrolimus trough levels of ≥10 ng/mL significantly faster than the control group (100% achievement in 14 days (Control) versus 4 days (T2); P = 0.01). Conclusion:  Performing a pre-transplant tacrolimus C2 does not significantly increase the high proportion of subjects achieving 10 ng/mL tacrolimus concentrations by day 3 using routine protocols. However, compared with standard care, performing a pre-transplant tacrolimus C2 does lead to patients achieving a whole-blood concentration of ≥10 ng/mL sooner.

48 Using a selective prostaglandin EP3 receptor antagonist selectively attenuated responses of mechanosensitive afferent nerves to urinary bladder distention and bladder

nociception either at central nervous system or at the peripheral level.49 High dose of protamine sulphate infused to rats intravesically for 2 weeks results in a loss of upper layer of urothelial cells, an increased of mast cells and PGE2 level, increase of urinary frequency,and decrease of voided volume.50 Urinary PGE2 levels were elevated in patients with UTI andsuccessful treatment for UTI lowers urinary PGE2 levels.51 In patients with OAB, urinary PGE2 level was also found to significantly increase and the PGE2 levels negatively correlated with

the maximum cystometric capacity.35 Recently, Yamaguchi et al. found that the urinary PGE2 level was significantly higher in patients with Inhibitor Library brain disease, with or without OAB symptoms, than in healthy controls. However, urinary see more NGF and substance P were not significantly associated with OAB as a result of brain disease.52 The role of urinary PGE2 on OAB needs further investigation. Adenosine triphosphate (ATP) and nitric oxide (NO) are released from the urothelium in the bladder. Munoz et al.53 reported that ATP release has a positive correlation, while NO release has a negative correlation with bladder contraction frequency in the rat. They suggested that urinary ATP/NO ratio may be a clinically relevant biomarker to characterize the extent of bladder dysfunction. Sugaya et al.54 further investigated whether the improvement of LUTS and urinary ATP level were related. Improvement of LUTS by treatment with alpha-1 receptor antagonist or

anti-muscarinic agent was related to decrease of urinary ATP/Cr ratio in patients with BPH or OAB. They suggested that measurement of urinary ATP can be used as a marker of pathologic bladder function. Tyagi and Chancellor proposed the hypothesis that local inflammation is a cause of and plays a central role in the etiology of the OAB. Tyagi et al.55 subjected urine from OAB patients through a test screen containing antibodies against 32 cytokines, chemokines, and growth factors to identify proteins with altered levels in their urine. A chronic feature of OAB makes it likely to be correlated with inflammation Exoribonuclease resulting from the body’s release of inflammatory cytokines as a result of irritation or injury.56 The physical signs of inflammation in OAB in the absence of UTI have been suggested by biopsy studies.57 Inflammation in the bladder typically involves lymphocytic mononuclear predominance restricted to the upper layers of the bladder wall, especially the sub-urothelium.58 Recent studies have shown that bladder inflammation induced by infiltrated immune cells can be further amplified by the resident cells of urothelium and detrusor through the release of chemoattractants called chemokines, such as MCP-1 and IL-8.

Importantly, simulated LipCl2MDP depletes inflammatory DCs and tolerogenic DCs with equal potency, with sustained protection arising through the dynamic regulation of these DC subsets under conditions of reduced inflammation. The up-regulation of tolerogenic DCs also contribute to the simulated anti-CD3 mediated efficacy in diabetic NOD mice [102], which is again characterized by the return of an apparently benign cellular infiltrate Venetoclax manufacturer [103]. In the case of anti-CD3, other mechanisms (e.g. induction of regulatory T cells) also contribute to sustained remission. The decision to represent a tolerogenic

DC phenotype illustrates how the broader immunology state-of-knowledge was brought to bear in reconciling NOD mouse results with buy MLN0128 the reported underlying biology. Conversely, it illustrates a gap in understanding based on available NOD mouse data and an area where additional data on NOD DCs could clarify the mechanistic underpinnings of these therapies. By selecting internal validation experiments that targeted

different biological components, the virtual mouse was fine-tuned along multiple biological axes, yielding a single parameterization that reproduces a wide array of behaviours. By itself, this was a non-trivial and insightful exercise. Furthermore, external validation experiments were selected to assess the virtual mouse response to distinct stimuli, thereby indicating whether fine-tuning is a necessary prerequisite in the simulation of an appropriate response. The virtual mouse reproduced outcomes accurately for 21 of 24 experiments, representing five interventions. This generally positive result suggests that the virtual mouse could be a valuable Farnesyltransferase counterpart to experimental investigations into novel therapeutic strategies (assuming the main mechanisms of action are within the scope of the modelled biology). The mismatches highlighted disparities in the published anti-CD40L data set that we had not appreciated previously. However, the potential importance of dose and

timing to outcomes, which were observed in the simulations, is entirely consistent with their importance in the experimental data, as highlighted in our 2004 review [1]. The model could, plausibly, be used to design experiments to reconcile disparate data. Additionally, dose/timing sensitivity argues that research efforts should use virtual mice whose disease progression (e.g. timing of diabetes onset) is aligned with the experimental mice and should evaluate a range of doses/timing to account for variability inherent in the data (i.e. NOD mouse colonies with variability in rate of disease progression) used to generate the model. While this model is intended to broadly support research efforts in the field of type 1 diabetes, like any other model it has limitations.

We have demonstrated that Gas6 expression in macrophages was blocked by LPS, and that the down-regulation of Gas6 also contributed to the LPS inhibition of phagocytosis. This result is consistent with a previous observation that Gas6-deficient macrophages exhibit impaired phagocytosis of apoptotic cells.26 Gas6 has been reported to mediate specifically phagocytosis of apoptotic cells by phagocytes.27,28 Accordingly, selleckchem we demonstrated that LPS inhibition of phagocytosis is restricted to the uptake of apoptotic cells. One key signal for engulfment of apoptotic cells is an externalized phosphatidylserine (PS) on the apoptotic cell surface.29

Gas6 binds, through its gamma- carboxyglutamic (GLA) domains, to PS exposed on cell surfaces.30 As a common ligand, Gas6 activates the TAM receptors through its carboxy-terminal immunoglobulin-like domains. Of these, Mer is critical for initiating Selleck Romidepsin phagocytosis signalling.27,31

Notably, Gas6 is a potent inhibitor of the production of pro-inflammatory cytokines, including TNF-α.32 It is reasonable to speculate that Gas6 may also facilitate phagocytosis through suppressing TNF-α. We noted a significant latency of the maximal inhibitory effect of LPS on phagocytosis in comparison to TNF-α. The reduction in the Gas6 level was also delayed in comparison to the induction of TNF-α in the medium after treatment with LPS. Therefore, we speculate that LPS-induced TNF-α is responsible for the LPS inhibition of macrophage phagocytosis in the earlier time after LPS treatment, and that LPS

suppression of Gas6 production is responsible for the inhibition of phagocytosis at a later time after the challenge. LPS induces TNF-α production in macrophages by activating TLR4. However, we showed that Gas6 expression in macrophages was suppressed by LPS in a TLR4-independent manner, as LPS suppression of Gas6 expression and inhibition of phagocytosis also occurred in TLR4−/− macrophages. This finding suggests that TNF-α and Gas6 act independently of one another in regulating the phagocytosis of apoptotic cells by macrophages. Understanding the mechanism underlying the LPS inhibition of Gas6 expression may have clinical implications. In conclusion, this article demonstrated that Immune system LPS inhibits the engulfing of apoptotic neutrophils by mouse peritoneal macrophages through LPS-mediated induction of TNF-α in a TLR4-dependent manner and suppression of Gas6 in a TLR4-independent manner in macrophages. These findings provide new insights into the role of inflammatory modulators in regulating phagocytic removal of apoptotic cells, which may be helpful in developing therapeutic approaches to the resolution of inflammation. This work was supported by the Special Funds for Major State Basic Research Project of China (Grant No. 2007CB947504) and the National Natural Science Foundation of China (Grant No. 30971459). The authors indicated no potential conflicts of interest.

The doses of raloxifene and oestradiol were chosen for their equipotent effects on BMD, and therefore it is possible that a higher dose of raloxifene could have activated the ERE to the same extent as oestradiol. The present study is the first to analyse the effects of CAIA on BMD and cartilage and bone remodelling. Sham-operated mice with CAIA, non-arthritic Ferroptosis phosphorylation OVX mice and OVX mice with CAIA displayed the same trabecular BMD. These results were unexpected, as

both OVX and CIA have been shown to induce bone loss separately and additively [9]. All mice had received an intraperitoneal injection of LPS 1 week prior to termination. LPS is well known to induce osteoporosis quickly [38,39]. Because we did not find any difference in BMD between the vehicle-treated mice that had received collagen-antibodies and the non-arthritic controls, osteoporosis may have been induced by the administration of LPS. Also, the duration of the experiment was 2 weeks after administration of antibodies, and this short observation time may conceal pro-osteoporotic properties of CAIA. This issue needs to be studied further. Interestingly, raloxifene treatment resulted in increased BMD, although it did not affect the severity of the arthritic disease, suggesting anti-osteoporotic properties by raloxifene during LPS-induced inflammation. In addition, raloxifene increased bone FK228 formation

as measured by serum levels of osteocalcin. This is in accordance with our previous results [6]. The histological Molecular motor destruction found in paw sections was not as severe as in some previous studies [10,12], and this was due most probably to the short experiment protocol (2 weeks of disease). Serum levels of COMP reflect the degree of cartilage destruction during arthritic disease [27–29]. To our knowledge, this has not been investigated previously in CAIA. The arthritic disease resulted in a significant increase in COMP levels in OVX mice compared to non-arthritic controls

(P < 0·001). As both groups had received an injection of LPS, administration of anti-CII antibodies contributed to the cartilage destruction. Indeed, it has been shown previously in vitro that anti-collagen II antibodies are pathogenic to chondrocytes, affecting both cartilage formation [40] and cartilage explants [41]. Administration of oestradiol and sham operation lowered the COMP levels compared to arthritic OVX controls, indicating protection of cartilage by both exogenous and endogenous oestradiol. In contrast, raloxifene did not influence the serum levels of COMP or the destruction of cartilage. It has been reported previously that raloxifene does not hamper granulocyte-mediated inflammation, whereas oestradiol does [19]. This could explain the difference between raloxifene and oestradiol treatment, as CII antibodies have been shown to mediate cartilage destruction even in the absence of inflammation [42,43].

2a,b). When we analysed VLA-5, we found that the relative numbers of cells expressing this receptor were not changed, as compared with controls. However, thymocytes from infected mice presented decrease VLA-5 density, particularly GSK126 ic50 in the CD4+ and CD8+ SP subpopulations (Fig. 2c,d). Both, DN and DP thymocyte subsets from P. berghei-infected mice exhibited a decrease in the relative numbers

of VLA-6+ cells, as compared with control animals. Membrane expression levels were also altered because DN, DP and CD8+ SP thymocytes showed a decreased density of VLA-6, as evaluated by the mean of fluorescence intensity (Fig. 2e,f). Overall, these data indicate that cell migration-related ECM integrin-type receptors are down-regulated in thymocyte subpopulations from P. berghei-infected mice. We also evaluated two selected chemokines produced by the thymic microenvironment, CCL25 and CXCL12,

as well as their corresponding receptors, CCR9 and CXCR4, expressed in thymocyte subsets. At 14 days post-infection, the thymi from P. berghei-infected mice showed a statistically significant increase in CXCL12 expression when compared with control thymi, as ascertained by quantitative PCR (Fig. 3a). Concomitantly with such increased CXCL12 relative gene expression, all thymocyte subpopulations from infected mice exhibited an increase BGJ398 in vitro in the relative numbers of cells expressing CXCR4 (Fig. 3b). Membrane expression levels were also higher in thymocytes from infected mice (except in CD8+ SP thymocytes), when compared with controls (Fig. 3c). In contrast, the analysis of CCL25 relative gene expression in the thymi from P. berghei-infected mice revealed decreased levels of mesenger RNA, when compared with controls (Fig. 3d). Moreover, the relative numbers of thymocytes expressing CCR9 were decreased in DN and CD8+ SP subsets, and increased in DP thymocytes (Fig. 3e). Nevertheless, membrane density of CCR9 Adenosine was higher in all thymocyte subpopulations from infected mice, when compared with control mice (Fig. 3f). To investigate a possible functional impact on thymocytes triggered by interactions mediated by selected ECM and chemokines, we analysed the migratory

response through fibronectin or laminin, or towards CXCL12 or CCL25, as well as the combined effect of each chemokine with one given ECM element. Overall, when we evaluated the bulk of migrating thymocytes, we found an enhanced higher migratory response of thymocytes from infected mice compared with controls (Fig. 4). This was seen in respect to laminin, CXCL12 and CCL25 applied alone, as well as to the combined stimuli of laminin with a given chemokine. The only exception was seen when fibronectin was applied alone: in this case the migration pattern was similar in both control and infected groups. Nevertheless, thymocytes from infected mice migrated significantly more than the control ones when fibronectin was combined with CXCL12 or CCL25.

“
“Aim:  Interleukin-6 (IL-6) is secreted from adipose tissue and thought to contribute to obesity-related disorders. The aim of this study

was to assess if IL-6-knockout (IL-6-/-) mice would develop obesity-induced renal impairment. Methods:  Wild-type (WT) and IL-6-/- mice were high-fat fed (HFF) for 16 weeks to induce obesity. At the end of the study, renal function was measured via albumin/creatinine ratio and serum creatinine levels, using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Glomerulosclerotic index (GSI) was scored in periodic acid Schiff-stained sections and collagen IV accumulation was assessed by immunohistochemistry. Renal cortical Rapamycin solubility dmso tumour growth factor beta (TGF-β1) activity and monocyte chemotactic protein-1 (MCP-1) levels were

measured via ELISA. Results:  Renal IL-6 concentrations were increased with obesity. Although both WT HFF and IL-6-/- HFF mice exhibited renal impairment as measured by increased serum creatinine and urinary albumin/creatinine ratios, this was exacerbated in IL-6-/- mice. Obese mice had renal activation of cortical TGF-β1, which was also higher in IL-6-/- mice. Collagen IV staining was not affected by obesity. GSI was increased with obesity in both LY2606368 price WT and IL-6-/- mice. Conclusion:  Obese IL-6-/- mice demonstrated renal functional and structural abnormalities above that seen in obese WT mice. We suggest that absence or low IL-6 levels may be an important accelerating factor implicated in the development and progression of obesity-induced

Elongation factor 2 kinase renal disease. “
“IgA nephropathy (IgAN) is recurrent after transplantation; however, its time of recurrence is unpredictable. To date, factors influencing IgAN recurrence have not been elucidated. We present a case of a 23-year-old man with end-stage renal disease (ESRD) who underwent living-related ABO-identical pre-emptive kidney transplantation (PEKT) using his 57-year-old mother as a donor. IgAN started when the patient was 19 years old, and renal biopsy revealed the usual pathological findings of IgAN. In spite of steroid therapy including steroid pulse and tonsillectomy, the patient developed nephrotic syndrome and progressed to ESRD in 4 years. Protocol biopsy on day 19 following PEKT revealed active recurrent IgAN. Nephrotic-range proteinuria and mild deterioration of kidney function developed regardless of strong immunosuppressive therapy such as steroid pulse, double filtration plasmapheresis and rituximab. We report a case of refractory IgAN that recurred 19 days after transplantation. This case is considered of value to elucidate factors leading to active IgAN recurrence. IgA nephropathy (IgAN) is the most common primary glomerulonephritis that causes end-stage renal disease (ESRD) in 20–40% of patients.[1] The success rate of kidney transplantation for patients with IgAN-induced ESRD was believed to be good.

Tunica vaginalis testis (pars parietal) is another tissue donor site that has the capability of being used both as flap and free graft.

In clinical practice, it has usually been used as a second layer for augmentation in a tabularized incision plate (TIP) in order to prevent subsequent urethrocutaneous fistula formation.[5] Also it has been used for correction of penile cuvature (chordee)[6] and surgical treatment of Peyronie’s disease.[7] Many experimental studies[8-12] and a few clinical studies[13, 14] have reported the feasibility and usefulness of using tunica vaginalis for definitive urethroplasty in anterior urethral strictures. The majority of those experimental studies Ipilimumab mw have revealed that tunica vaginalis mesothelium was gradually replaced by a more stratified epithelial lining similar to the urethral lining of the native urethra. In the current study, we retrospectively evaluated the clinical efficacy and feasibility of tunica vaginalis (TV) pedicle flap for reconstruction of anterior urethral stricture by comparing some clinical

parameters including the urinary flow rate (Qmax), international prostate symptom score (IPSS), patients quality of life (QoL) and residual urine (RU). The pre-operative result was compared 3 and 12 months postoperatively. selleck screening library After obtaining institutional ethical review board approval, 15 male patients who had undergone Tunica vaginalis pedicle flap urethroplasty between January 2006 and January 2011, were retrospectively assessed. The procedure was allocated for patients who had not enough penile skin, including those who had previous

failed attempts of urethroplasty and those who had already underwent circumcision. Before surgery, the length of stricture was determined according to radiology reports and conventional retrograde urethrography plus voiding cystourethrography. During surgery, it was measured, using centimeter ruler. The urethroplasty had been done with two different techniques: TV pedicle flap ventral on lay urethroplasty (nine patients), and TV pedicle flap tubularized ID-8 substitution urethroplasty (six patients). In order to assess the clinical efficacy and success rate of the surgical technique, the pre-operative Q(max), IPSS, QoL, RU were compared with them 3 and 12 months postoperatively. In order to know if there was change in caliber of urethra over time, the comparison was done between them at 3 and 12 months postoperatively. The t-test was used for statistical analysis. Moreover, pre-operative and postoperative retrograde urethrography was compared (Figs 1, 2). Van Buren urethral sounds (16–18 Fr) were used for checking and dilating the reconstructed part at 3 month intervals after surgery. Finally, Fisher’s exact test was used to find any difference between success rates of two aforementioned surgical techniques. Under epidural anesthesia the patient was placed in the lithotomy position.

Vaccine development remains an elusive and coveted breakthrough. Several strategies have been tried over the past 40 years, addressing all stages selleck chemical of the life cycle in both whole-organism and recombinant subunit models. The use of radiation-attenuated sporozoites 21 is the only model that has consistently generated reproducible sterilizing immunity in humans and describing it as the “gold standard” of malaria vaccines has become an oft-repeated and

tired but nonetheless accurate phrase in the literature. In this model, sporozoites are subjected to gamma-radiation to cause random genetic mutations, and when injected into mouse and man, accumulate in the host liver, causing resistance to subsequent infections with wild-type parasites; however, despite the similar outcomes of genetically-modified parasite lines, it is debatable whether such whole-organism vaccines can be conceivably manufactured en masse to the market or pass the rigors of safety regulators. Nonethless, people are trying, and Sanaria Inc’s endeavours are ongoing to produce sterile, purified

and cryopreserved radiation-attenuated sporozoites; however, doubts as to the viability of the whole-organism model have paved the way for recombinant subunit vaccines based on immunodominant malarial antigens. One example of this, RTS, S/AS02A, the vaccine based BMS-777607 nmr on the Plasmodium falciparum circumsporozoite protein, developed by GlaxoSmithKline, has elicited

efficacies ranging from 40 to 60% in Phase III clinical trials and, this is, by all accounts, the best we have so far. Thus in immunology the connection between Plasmodium as a science and malaria as a disease is most apparent, and in the field of vaccinology the link between malaria disease and its impact on the human condition are clearest of all. But can we as basic researchers reconcile the yearly million-fold deaths to the exciting data from our FACS stains and ELISPOTs that will surely ensure that the next paper O-methylated flavonoid is accepted by a high-ranking journal? Perhaps some can, some cannot, and for others it does not even matter. All I know is that these two worlds collided quite symbolically for me last December outside the lab, in the form of that unfortunate gentleman in the corridor. The explanation for his condition was that he was presenting himself to the Tropical Medicine clinic of the University Hospital, with whom the research staff share lab and corridor space. Having just returned from a business trip to the Sudan, he was feeling under the weather, feverish, weak and not himself, and decided the best option would be to return to the clinic that had originally given him advice before his travels. Some 15 minutes later, this man was being maneuvered onto a stretcher and treated immediately with intravenous administration of artesunate. We learned later that he had P. falciparum infection with a blood parasitemia of 16%.