At the end of the study period (April 2012), all but one patient survived and all flaps remained viable. One patient expired due to local recurrence of angiosarcoma, 4 months after chemotherapy and radiotherapy. Table 1 is a summary of

all nine patients’ data. In July 2008, a 40-year-old male patient with a history of epilepsy presented with rupture of an intracranial arterio-venous malformation in the temporoparietal lobe, for which an emergent decompression buy GSI-IX craniectomy was performed. Four months later, the patient underwent cranioplasty using prosthesis for cranial vault resurfacing and a local advancement scalp flap for coverage. Prosthesis exposure developed subsequently and this problem persisted despite another two advancement procedures in the following year (Fig. 1). The patient was then referred for scalp reconstruction, for which a free ALT flap was used for the final defect, measuring 15 × 6 cm2 (Fig. 2). Microvascular end-to-end anastomosis was performed to the right superficial temporal artery and vena comitants using 9-0 nylon, while the thigh donor-site was closed primarily. At 1-month follow-up, the flap healed uneventfully, and the patient was discharged without complications (Fig. 3). This 36-year-old male was involved in multiple traumas and suffered from head

injury 10 years ago, during which he underwent craniectomy followed by cranioplasty using selleck prostheses. He presented in December of 2011 with an exposed and infected prosthesis at the left temporoparietal area. Following excisional debridement and removal of the prosthesis, a scalp defect measuring 30 × 7 cm2 was noted (Fig. 4). A free ALT flap was performed via end-to-end anastomosis to the left facial artery and vein. The Y-27632 molecular weight left thigh donor site was closed primarily.

At 1 week, the distal flap tip developed necrosis and required debridement of a 2.5 cm segment, followed by a small Z-plasty to close the defect. Subsequent healing proceeded uneventfully at 1-year follow-up (Fig. 5). For uncomplicated small- to moderate-sized defects, local flap coverage is the best option for reconstruction, typically involving a single or multiple transposition procedures depending on the defect size and location.[23, 24] However, local and regional flaps reach their limit when defects extend beyond 200 cm2, especially when compounded by complications such as infection, radiation therapy, multiple prior surgeries and composite tissue and bone loss. Although tissue expansion has been proven to be successful for resurfacing large scalp defects, its role is limited due to the requirement of prior planning, patient compliance, and absence of infection. In complex cases, only well-vascularized free-tissue transfer can meet both structural and protective requirements, albeit resulting in a hairless reconstruction.

The MyD88-dependent pathway involves the early-phase activation of NF-κB, all the TLRs except TLR3 have shown to activate this pathway. TLR3 and TLR4 act via MyD88-independent pathway with delayed kinetics

of NFκB activation [21]. MyD88 plays an important role during myeloid cell differentiation Protease Inhibitor Library mw and found to be essential for M. tb-induced macrophage activation [22]. Ligand binding leads to TLR dimerization and conformational change, which then associates with the adaptor MyD88 and interacts with the IRAK-4 via their respective death domains [23-26]. Once IRAK-4 binds to MyD88, it recruits and phosphorylates IRAK-1, which activates the kinase function of it. IRAK-1 then autophosphorylates itself, recruiting tumour necrosis factor receptor–associated factor-6 (TRAF6) to the MyD88/IRAK-4/IRAK-1 complex. Next, IRAK-1 and TRAF6 dissociate from the receptor complex and interact with additional molecules, resulting in c-Jun N-terminal kinase (JNK) and inhibitor of κB kinase (IKK) activation. These proteins then induce activator protein-1 (AP-1) and NF-κB (P50, P65) activation, ultimately leading NVP-BGJ398 in vitro to the transcription of genes encoding proinflammatory cytokines such as TNFα, IL-6, IL-8, IL-1β and chemokines [27](Fig 1). TIR

domain-containing adapter protein inducing IFN-β (TRIF, also known as TICAM1) was found to mediate the MyD88-independent pathway. The TRIF-related adapter molecule (TRAM, also known as TICAM2) specifically acts to bridge TLR4 with TRIF [28, 29]. TLR4 and TRAM get delivered to the endosome and subsequent recruitment of TRIF precedes the initiation [30], which involves the non-canonical IкB kinases Vildagliptin (IKKs), TANK binding kinase 1 (TBK-1) and IKKε/IKKi that induces interferon regulatory-3 (IRF-3) phosphorylation thus leading to the activation of IRF-3, and thereby induces IFN-β. It, in turn, activates Stat1, leading to the induction of several IFN-inducible

genes [31-33]. IRF-3 may also associate with canonical IKKs composed of IKKα and IKKβ, both of which phosphorylate Ser32 and Ser36 of IкBα, thereby inducing NF-кB activation [27] (Fig 1). SNPs are single-allele mutations in the genomic sequence of an organism, which are responsible for about 90% of all human DNA variation and play an important role in human evolution, drug sensitivity and disease susceptibility [34] Synonymous SNPs are those with different alleles encoding for the same amino acid (silent mutation). Non-synonymous SNPs (nSNPs) have different alleles that encode different amino acids. Both synonymous and non-synonymous SNPs influence promoter activity and pre-mRNA conformation (or stability). They also alter the ability of a protein to bind its substrate or inhibitors [35] and change the subcellular localization of proteins (nSNPs).

The haemolytic activity of several microorganisms is considered a factor that contributes to pathogenicity of the organism to humans and animals. This virulence factor was previously identified in several pathogenic fungi that cause systemic mycoses, such as Aspergillus and Candida. In this study, the haemolytic learn more activity of six major Malassezia species, including M. furfur, M. globosa, M. pachydermatis, M. restricta, M. slooffiae and M. sympodialis, was investigated. The haemolytic

activity of these species was tested on tryptone soya agar with 5% sheep blood. All the examined Malassezia species produced a halo zone of complete haemolysis. A quantitative analysis of the haemolytic activity was performed by incubating sheep erythrocytes with the extraction from culture of each Malassezia species. Interestingly, M. globosa and M. restricta showed significantly high haemolytic activity compared with the other Malassezia species. In addition, M. globosa also exhibited stable haemolytic activity after treatment at 100 °C and in the presence of some proteases, indicating that this haemolytic factor is different from those NVP-LDE225 chemical structure of other fungi. “
“Invasive mould infections (IMI) are associated with significant morbidity and mortality. In vitro studies have demonstrated that hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins)

have activity against several pathogenic moulds including Zygomycetes and Aspergillus spp. The aim of our study was to determine if statin use is a preventive factor for the development

of IMI. This was a retrospective case–control study of 10 United States Veterans Affairs Medical Centers that comprise the Veterans Integrated Service Network (VISN) 16. Cases with IMI and controls were identified from 2001 to 2008. Controls were matched by age, facility, history of transplantation, presence of chronic steroid use and presence of human immunodeficiency virus infection (HIV). Two hundred and thirty-eight patients were included. Independent variables associated with the development GPX6 of IMI were history of solid malignant tumours (OR 2.63, 1.41–4.87) and hypertension (OR 2.29, 1.13–4.68). Statin use within 3 months of index date was not an independent variable for prevention or development of IMI. No level of exposure to a statin drug appeared to influence the development of infection. This retrospective case–control study suggests that despite evidence of in vitro activity, statins may not decrease risk of IMI. Prospective, controlled trials may be necessary to investigate any potential clinical benefit. “
“Paracoccidioidomycosis (PCM) is the most important systemic mycosis in Latin America. It has been regarded as a multifocal disease, with oral lesions as the prominent feature.

Type 2 DM Mellitus was the commonest cause 53.3% (n = 8) of ESRD in patients with PAD.On univariate analysis, PAD was found to be significantly associated with age >40

years (p value = 0.003; OR = 14.8; CI = 1.75–125.27), Type 2 DM (p value = 0.009; OR = 5.4; CI = 1.44–21.14), parasthesia of lower limbs (p value = 0.001; OR = 10; CI-2.31-43.16), and intact PTH > 300 ng/ml (p value = 0.006; OR = 5.7; CI = 1.55–21.50). However on multivariate analysis only parasthesia of lower limbs and intact PTH >300 ng/ml were significantly and independently associated with PAD, while other variables were not significant. Conclusion: Peripheral arterial disease was common occurrence in ESRD patients on hemodialysis. ABI needs to be included as the a routine assessment in ESRD patients. SUFIUN ABU1, RAHMAN ASADUR1, KITADA KENTO1, FUJISAWA YOSHIHIDE2, selleck kinase inhibitor NAKANO DAISUKE1, RAFIQ KAZI1, NISHIYAMA AKIRA1 1Department of Pharmacology, Faculty of Medicine, Kagawa University; 2Life Science Research Center, Faculty of Medicine, Kagawa University, Japan Introduction: To test the hypothesis that high salt intake aggravates

hypertension and alters dipping pattern of blood pressure through renal sympathetic nerve activation in chronic kidney disease (CKD), effects of high salt and renal denervation on blood pressure in adenine-induced renal injury model rats. Methods: Four-week-old Wistar rats

were underwent uninephrectomy followed Autophagy signaling inhibitors by renal sympathetic denervation (RDX) and implantation of telemetry device at 5 weeks of age. After one week recovery, adenine (200 mg/kg/day, p.o.) was administered for 2 weeks. Then, high salt diet (8% NaCl) and low-salt diet (0.3% NaCl) were treated for 1 week, respectively. Results: High salt diet increased mean arterial pressure (MAP) (from 106 ± 4 to 158 ± 5 mmHg, P < 0.01) in adenine-treated rats, but RDX did not affect high salt-induced increases RG7420 purchase in MAP. Interestingly, after switching from high salt to low salt diet, MAP returned to respective pre-treatment level within 2 days in both RDX and non-RDX adenine-treated rats. Adenine-treated rats showed normal dipping pattern; however, high salt feeding for 1 week resulted in non-dipper pattern of MAP. In these animals, dipping pattern was normalized after switching to low salt diet. On the other hand, RDX did not show any changes in dipping pattern during high or low salt intake. Conclusions: These data support the hypothesis that high salt intake aggravates hypertension and alters dipping pattern of blood pressure in CKD. However, our data suggest that renal sympathetic nerve does not play a predominant role in this pathological process.

Mizoribine (MZR) is a selective inhibitor of the inosine monophosphate dehydrogenase – a key enzyme in the de novo pathway of guanine nucleotides – that was developed in Japan.[1] Clinically, MZR has been successfully used without any serious adverse effects

for the long-term treatment of young patients with lupus nephritis.[1-3] Besides its immunosuppressive effects, MZR has recently been reported to suppress the progression of histologic chronicity in selected patients with lupus nephritis and immunoglobulin A (IgA) nephropathy.[1-4] Moreover, some experimental reports described that MZR attenuates tubulointerstitial fibrosis in Z-VAD-FMK rat models of unilateral ureteral obstruction, non-insulin-dependent diabetes and peritoneal fibrosis via suppression of macrophage infiltration of the interstitium.[5-7] Also, we recently confirmed a significant suppression of intraglomerular macrophage infiltration accompanied with significant suppression of the chronicity indices following MZR treatment in a patient with proliferative lupus nephritis.[8] These laboratory

and clinical observations suggest another beneficial mechanism of action of MZR from the histologic standpoint in the treatment of lupus nephritis. Since most of the oral dose of MZR is excreted unchanged in urine,[9] the Ixazomib drug is thought to expose directly to residual renal cells. Thus, it is important to examine the direct effects of MZR against inflamed residual renal cells.[10] Glomerular mesangial cells (MCs) have been reported to produce a wide variety of proinflammatory molecules that play an important role in immune and inflammatory reactions in the kidney, and MCs itself are thought to play a pivotal role in the pathogenesis of renal diseases.[11]

Interestingly, it has been reported that the implication of ‘psuedoviral’ immunity as a novel disease concept of lupus PLEK2 nephritis, that is, the detection of self-nucleic acid particles resembling viral particles by toll-like receptors (TLRs) results in the activations of the downstream signalling cascades and subsequent type I interferons (IFNs) production.[12] In this context, we have examined the TLR3 signalling cascades treated with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of viral dsRNA, that makes ‘pseudoviral’ infection in cultured human MCs, and found that the activation of mesangial TLR3 upregulated the expression of functional molecules including monocyte/macrophage chemoattractants: CC chemokine ligand (CCL) 2 (or monocyte chemoattractant protein-1 [MCP-1]), CCL5 (or regulated on activation, normal T-cell expression and secretion [RANTES]), CXC ligand 10 (CXCL10) (or IFN-γ-induced protein 10 [IP-10]), fractalkine (or CX3CL1), and neutrophil chemoattractant: interleukin (IL)-8 (or CXCL8), in cultured human MCs.

tuberculosis (Gioffréet al., 2005; Senaratne et al., 2008). Like mce3 mutants of M. tuberculosis, mice infected with RD1 mutants had increased survival with reduced virulence and pathogenesis, as compared with wild-type M. tuberculosis (Hsu et al., 2003; Lewis et al., 2003). Furthermore, immunological characterization of RD1 proteins in humans using overlapping synthetic peptides in cell-mediated immunity (CMI) assays has identified three major proteins (ESAT-6, CFP10 and PPE68) with potentials for the diagnosis and development of new vaccines against TB (Okkels et al., 2003; Mustafa,

2005a, b; Hanif et al., 2008; Mustafa et al., 2008). However, mce3 operon containing RD15 region has not yet been characterized Cabozantinib supplier for identification ZD1839 molecular weight of antigens useful in diagnostic or vaccine applications. It has been suggested that CMI responses are responsible for both protection and pathogenesis

in TB (Dietrich et al., 2006; Mustafa, 2009c). Protective CMI primarily involves interferon (IFN)-γ release by antigen-activated CD4+ T-helper (Th) type 1 cells, which activates macrophages to destroy intracellular mycobacteria (Flynn, 2004). The central role of IFN-γ in the protection against TB has been suggested by many studies in both animals and humans (Flynn, 2004; Al-Attiyah et al., 2006a; Dietrich et al., 2006; Mustafa et al., 2006). On the other hand, the Th2 responses, characterized by the secretion of interleukin (IL)-4, IL-5 and anti-inflammatory cytokine IL-10, are associated with a lack of protection (Bai et al., 2004; Flynn, 2004). In particular, IL-10 is associated with reduced resistance and chronic progressive TB in the murine model (Turner et al., 2002). Furthermore, IFN-γ : IL-10 ratios provide a useful objective marker of disease activity in TB and can be important in disease management (Salina from & Morozova,

2004; Jamil et al., 2007). In response to mycobacterial antigens, high IFN-γ : IL-10 ratios correlate strongly with protection and TB cure, whereas low ratios correlate with disease severity and pathology (Salina & Morozova, 2004; Jamil et al., 2007). Therefore, the ability to stimulate strong IFN-γ release and higher IFN-γ : IL-10 ratios were used in this study as criteria for the identification of M. tuberculosis-specific protective antigens encoded by genes in RD15. In this study we have characterized the proteins of RD15 for CMI responses by determining their Th1 (antigen-induced proliferation and IFN-γ secretion) and anti-inflammatory (IL-10 secretion) reactivity using peripheral blood mononuclear cells (PBMC) obtained from TB patients and healthy subjects. Furthermore, IFN-γ : IL-10 ratios were calculated to determine the Th1 vs. anti-inflammatory bias of the responses.

2d). When we performed correlation analysis to find the relationship between this population and disease activity, it did not reach statistical significance because the number of patients with active SLE was not great enough (data not shown). However, linear regression analysis showed that the proportion of CS1-positive B cells increases linearly with increased SLEDAI score (P = 0·035, R2 = 11·4%; Fig. 2e). Because the proportion of cells can be affected by a relative lymphopenia in patients Selleck X-396 with SLE, we also determined the mean fluorescence intensity ratio (MFIR),

which represents the density of receptors at the single-cell level (Table 2). MFIR of CS1+ cells in total PBMCs was not significantly different between healthy controls and SLE patients. However, CD3+ CS1+ T cells up-regulated CS1 expression significantly at the single-cell level. In contrast, all NK cells down-regulated CS1 expression significantly compared to healthy controls. For analysis of B cells, we gated total B cells including both CS1-positive and CS1-negative

B cells, because percentages of CS1-positive B cells are very low in healthy controls. Despite the significant percentage increase of CS1-positive B cells, MFIR Selleck Nivolumab shift in CS1+ cells gated within total B cells did not reach significant levels compared to healthy controls. Collectively, these data suggest that CS1-expression is regulated dynamically at the cellular and molecular levels in SLE. Recently, a number of different subsets of circulating B cells were reported in SLE, including naive B cells, memory B cells, plasma cells and plasmablasts. These cells can be identified by surface markers such as surface immunoglobulins (IgM and IgD), CD19, CD20, CD21, CD27, CD38, CD95 and human leucocyte antigen D-related (HLA-DR). Interestingly, we found that CS1 expression can also identify different subsets of SLE B cells.

Figure 3 shows that co-staining with CD19 and CS1 distinguishes three distinct subsets of B cells: CD19-middle, CS1-negative B cells; CD19-high, CS1-low B cells; and CD19-low, CS1-high B cells (best illustrated by Fig. 3d). As shown in Fig. 3a–c, healthy individuals had CD19-middle, CS1-negative B cells as a major B cell population. In contrast, most SLE patients had all three B cell populations, and all patients exhibiting a high proportion of Cediranib (AZD2171) CS1-positive B cells essentially had CD19-high and CD19-low B cell populations. As shown in Fig. 3e,f, some SLE patients displayed CD19-low, CS1-high B cells as their major B cell populations. Notably, as seen in Fig. 3f, one patient with active SLE (patient 1, SLEDAI = 15) displaying the highest percentage of CD19-low, CS1-high B cells had a very low number of CD19+ B cells, probably affected by lymphopenia. Next, we analysed the proportion of 2B4-expressing cells in total PBMCs, CD3+ T cells, CD56+ NK cells and CD14+ monocytes in patients with SLE and healthy controls. As shown in Fig.

Despite being immortalized, HTR-8/SVneo cells have retained all the phenotypic and functional characteristics

of the parental selleck chemical mortal HTR-8 cells. The expressing markers of EVCT in situ are cytokeratins 18 and 8, human placental lactogen (hPL), human chorionic gonadotropin (hCG), human leukocyte antigen G (HLA-G) and type IV collagenase. Meanwhile, another immortalized primary cell clone (HPT-8) exhibited cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, oestradiol, progesterone and hCG and were positive for HLA-G, a marker of extravillous trophoblasts.[14] These cells are permissive for the full replication cycle of human cytomegalovirus.[15, 16] These features make HTR-8/SVneo and HPT-8 cells as an ideal in vitro model for studying the biology of normal trophoblasts. Between October 2005 and January 2009, we recruited women who underwent induced abortion or experienced spontaneous abortion at Nanjing Maternity and Child Health Care Hospital. All of the women were asked about the number of previous FDA approved Drug Library ic50 miscarriages, the number of stillbirths and the total number of previous pregnancies, and had placental villi and blood samples drawn. The same questionnaire was translated into the native

languages of the women and was used with participants from Nanjing Maternity and Child Health Care Hospital. The study included participants born in the same country who were all over 18 years of age. Women (n = 30) who had a previous history of spontaneous abortion, that is, (i) a history of two or more consecutive spontaneous abortions in the first trimester and (ii) an unexplained aetiology of spontaneous abortion with unexplained vaginal bleeding at 6-8 weeks of gestation, and for whom pregnancy

loss was confirmed by ultrasound scan were considered part of the spontaneous abortion group. Their average age was 28.8 years, and the average gestational age was 56.4 days. These subjects were age- and sex-matched Proteases inhibitor with 30 apparently healthy pregnant women who had no abnormal gynaecological history at 6–8 weeks of gestation and who wanted to have an induced abortion (control group). Their average age was 27.8 years, and the average gestational age was 56.6 days. These women voluntarily sought abortions for family planning purposes. Live pregnancy was confirmed by ultrasound scan. All of the women had regular menstrual cycles, and the gestational age estimates based on the last menstrual period was confirmed by the ultrasound scan. Termination of pregnancy was surgically achieved by vacuum suction as approved by the Ethical Committee of the Chinese Academy of Sciences and Nanjing Maternity and Child Health Care Hospital in Nanjing.

Thus, TRO19622 appears to be able to partly compensate for the multifactorial nature of the disease and is currently undergoing clinical trials

in ALS. Aberrant mitochondrial fragmentation and rounding up are observed in ALS [115,116]. A small molecule has been identified that regulates mitochondrial dynamics Cilomilast by interacting with Drp1 and inhibiting mitochondrial fission in vitro and in vivo[143]. It is possible that other approaches can be developed that will modulate mitochondrial fission and fusion, which can be used to block the mitochondrial fragmentation observed in ALS. Furthermore, drugs that modulate the intracellular calcium cycle might be beneficial in light of alterations in calcium handling in models of

ALS. It is appreciated that ALS is a complex and multifactorial disease, with multiple interacting pathogenic processes exacerbating the dysfunction and consequent degeneration of the motor neurone. A wealth of evidence has now implicated mitochondria as having a critical role in motor neurone degeneration, with perturbations including oxidative stress, excitotoxicity, apoptosis and aberrant trafficking of the organelle. As discussed, it is currently unclear whether this mitochondrial dysfunction is causal, contributory or a consequence of the motor neurone Stem Cell Compound Library cell assay degeneration. It is evident that upon initiation of mitochondrial dysfunction, the aforementioned pathogenic processes become self-sustaining and self-propagating, and diminish the potential efficacy of therapeutic interventions. Therefore, it is imperative to elucidate the pathogenic chain of events in ALS in order to effectively target therapeutic intervention to the primary and secondary events in the degenerative process. The notion of ALS as a multifactorial

disease BCKDHA necessitates the identification of therapeutic agents capable of targeting several pathways simultaneously. This may perhaps explain the relative clinical shortcomings of Riluzole, which only targets the glutamatergic pathway. Thus, in the future, the focus of the search for ALS therapeutic compounds is likely to be on identifying effective cocktails of therapeutic agents, or a novel compound targeting several of the pathogenic pathways known in ALS. Work in the authors’ laboratories is supported by grants from the MRC, Wellcome Trust, National Institute for Health Research, Motor Neurone Disease Association, BBSRC, NC3Rs, European Union under the seventh Framework Programme for RTD – Project MitoTarget, and Alzheimer’s Research Trust. “
“Angiomatous meningiomas are rare meningioma subtypes, which are characterized by abundant, well-formed vessels. We encountered two cases of newly diagnosed angiomatous meningiomas exhibiting tumor cells with brown pigments, which were histochemically proven to be iron.

In general, mammals act as apex predators in tapeworm life cycles, playing host to adult, enteric stages. In the unique case of taeniid cyclophyllideans, in which

mammals also act as intermediate hosts (24), they are the primary prey items of larger mammals, such as in the rodent/fox cycles of Echinococcus, Mesocestoides and some Taenia species (25). With regard to human infection with tapeworms, there is at least some evidence that the Taenia species infecting humans evolved before the development of agriculture, animal husbandry and the domestication of cattle and swine (24,26), indicating that humans were responsible for introducing Taenia solium and T. saginata BMS-354825 to contemporary agricultural cycles. Moreover, phylogenetic analysis showed that these species evolved in humans independently (26): T. solium associated with the tapeworms of hyenas and T. saginata with those of lions.

This unsettling scenario suggests that in prehistoric times, food webs selected a role for ourselves not only as definitive hosts, but also as intermediate hosts, in transmission cycles including larger carnivores as the apex predators. Table 1 summarizes the general characteristics of tapeworm genomes as represented by three taeniid and one hymenolepidid cyclophyllidean species. At present, the only published flatworm genomes are those of the human bloodflukes Schistosoma mansoni (27) and S. japonicum (28), but available draft data for the planarian model Schmidtea mTOR inhibitor Rebamipide mediterranea (29) and the ‘turbellarian’Macrostomum lignano (30) provide important reference genomes of free-living flatworms. By comparing parasitic and free-living species, identification of both loss and expansion of gene families will provide the most comprehensive picture to date of the effects of evolving obligate parasitism, allowing its signature to be compared with that in other animal groups, such as the nematodes (31). Much of this signature will surely relate factors evolved to counter host immune defences, and comparative genomics thus hold great promise for advancing the

immunology of parasitic flatworms. Tapeworm genomes are small in size at ∼110 Mb, compared with 363 Mb in Schistosoma (27), 700 Mb in Schmidtea and ∼330–1100 Mb in Macrostomum (http://www.genomesize.com/index.php). Differences may be due to the fact that tapeworm genomes contain fewer mobile genetic elements and retroposons than trematodes or planarians, in which they are common (32,33). However, it is clear that there has also been significant gene loss. For example, the components for de novo synthesis of cholesterol are missing, as is ornithine decarboxylase (a key enzyme in spermidine/putrescine biosynthesis), and these essential components must therefore be acquired from the host. Indeed, the complete loss of a gut has presumably resulted in the loss of many enzymes.