The up-regulation of TLR-2 and/or TLR-4 has been shown in macrophages and gingival fibroblasts of inflamed periodontal tissue [15], which suggests that innate immune responses involving the TLRs as signalling receptors contribute to the inflammatory or immune response of periodontal tissue. Sirtuin 1 (SIRT1) is the human orthologue of the yeast Sir2 protein, the prototypic class III histone deacetylase. SIRT1 has been shown to play a central role in a variety of cellular processes such as stress resistance, metabolism, differentiation and ageing [16]. We have demonstrated previously that SIRT1 exerts anti-inflammatory

effects through R788 manufacturer the modulation of osteoclastogenic cytokine levels in human PDL cells [17]. Furthermore, SIRT1 has been implicated in the regulation of immune function, as it is expressed at high levels in the thymus, GSK-3 beta phosphorylation including in CD4+ and CD8+ thymocytes, and knocking out SIRT1 increases sensitivity to ionizing radiation-induced apoptosis [18]. Moreover, treatment of T cells with resveratrol, a SIRT1 activator, suppresses proliferation and cytokine production

in vitro[19]. Resveratrol also suppresses immune functions by inducing lymphocyte apoptosis [20]. These results suggest that SIRT1 may be involved in the production of immune defence genes in MS-stimulated PDL cells. We have reported previously that MS induces inflammatory cytokines including IL-1β, TNF-α and IL-6, as well as defence genes such as haem oxygenase-1 (HO-1), in human dental pulp cells [21]. Recently, we demonstrated that MS modulates odontoblastic/osteoblastic differentiation via modulation of the HO-1 pathway in dental pulp and PDL cells [22,23]. Although the activation of TLRs and production of anti-microbial peptides, cytokines and chemokines, as well as their receptors, are implicated in innate and adaptive immunity [24], there is little information on the involvement of SIRT1 in MS-induced immune genes of PDL cells. The aim of the present study was to investigate

the role of SIRT1 in the effects of MS on the expression Ureohydrolase of immune response genes in human PDL cells and to identify the underlying mechanisms involved. Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS) and other tissue culture reagents were purchased from Gibco BRL (Grand Island, NY, USA). Resveratrol and sirtinol were purchased from Sigma-Aldrich (St Louis, MO, USA). Affinity purified polyclonal antibodies against mouse TLR-2, TLR-4, I-κBα, nuclear factor (NF)-κB p65 and β-actin monoclonal antibodies were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Antibodies against phospho-extracellular-regulated kinase (p-ERK), ERK, phospho-p38 (p-p38), p38, phospho- c-Jun N-terminal kinase (p-JNK) and JNK were purchased from Cell Signaling Inc. (Beverly, MA, USA).

Eravani and S. Alizadeh (Pasteur Institute of Iran). Special thanks to Dr Nariman Aghaei Bandbon Balenga (Medical University of Graz) for helpful

discussion on neutrophil isolation. Financial support was Pirfenidone order provided by Iran Ministry of Health and Pasteur Institute of Iran. “
“Recurrent miscarriage (RM) is the occurrence of three or more consecutive miscarriages before gestational week 20 and is a condition that affects 1–3% of women [1]. RM can be classified into two categories: primary RM (no prior live birth) or secondary RM (three or more consecutive miscarriages following a live birth). In addition to genetic and anatomical factors causing RM, many studies have suggested that signs of autoimmunity and dysregulation of natural killer (NK) cell immunity characterize women with RM. Approximately 25 years ago, the first pilot studies on the use of intravenous immunoglobulin (IVIg) for the treatment of RM were conducted and reported a live birth rate of 80–82% [2, 3], which provided support to warrant further investigation in placebo-controlled trials. In 2006, a Cochrane review Selleck Panobinostat of IVIg treatment for RM in

eight placebo-controlled trials with 303 RM patients was conducted, concluding that IVIg did not increase live birth rates when compared to placebo [odds ratio (OR) = 0·98; 95% confidence interval (CI) = 0·61–1·58] [4]. However, this review did not differentiate between primary and secondary RM patients. Separate analysis of these two subsets of RM patients may be necessary, as several studies have observed that secondary RM is a condition dominated by immunological risk factors when compared to primary RM, suggesting large heterogeneity between these two subgroups. Tumour necrosis factor (TNF)-α is a cytokine involved in the immune system’s inflammatory response. Piosik et al. analysed peripheral blood samples of RM patients taken at gestational week 5, and found that TNF-α levels were increased significantly in secondary RM patients compared to primary RM patients (P = 0·042) [1]. This indicates that Nintedanib (BIBF 1120) secondary RM is a condition with an increased proinflammatory

response in early pregnancy. More evidence of the role of immunological factors in secondary RM has been reported in studies that have shown associations between secondary RM patients with specific maternal human leucocyte antigen (HLA) polymorphisms. Kruse et al. found that there was a significantly higher prevalence of the HLA-DRB1*03 allele in secondary RM patients compared with controls (OR = 1·8; 95% CI = 1·3–2·5) [5], whereas the allele was not increased in patients with primary RM. A previous pregnancy with a boy can be a risk factor for secondary RM. In general, maternal immune recognition of male-specific minor histocompatibility (HY) antigens expressed in male fetal and trophoblast cells is well tolerated, resulting in a live birth. However, pregnancy with a boy may prime the mother’s HY immunity.

Plasmacytoid DC (pDC) are bone marrow-derived leukocytes that secrete type I IFN (IFN-I) 1, 2. pDC detect selleck products RNA and DNA from viruses and RNA/DNA/immunocomplexes through two endosomal sensors, TLR7

and TLR9, respectively, both of which induce secretion of IFN-I through the MyD88-IRF7 signaling pathway 3–5. pDC were first identified in humans as CD4+, CD68+ and IL-3R+ (CD123) plasma cell-like cells 6. Initially, it was unclear what functions these cells perform in vivo; however, pDC’s prominent endoplasmic reticulum suggested a role in cytokine secretion. Later, it was demonstrated that this unique subset could differentiate into Ag-presenting cells 7, 8 and specialize in the secretion of IFN-I, thus corresponding to the human natural IFN-producing cells 9, 10. In 2001, cells that resembled human pDC were finally identified in the mouse 11. pDC originate in the bone marrow from common lymphoid/myeloid progenitors and are dependent on Flt3L, STAT3 and the transcription factor E2-2 for development 12. pDC, similar to committed precursors of classical DC, enter lymphoid organs directly from the blood through the high endothelial venules 13–15. Under homeostatic R788 order conditions, pDC also inhabit mucosal tissues and organs, albeit at low numbers. pDC accumulation in lymphoid tissues, mucosa and organs occurs during several human pathologies, particularly in LN of patients affected by

sarcoidosis, Mycobacterium tuberculosis infection 16, Kikuchi’s disease 17, and in the skin of patients affected by psoriasis 18, 19, systemic lupus erythematosus (SLE) 20 and lichen planus 21, 22. pDC accumulation has also been observed in brain lesions of patients with multiple sclerosis 23, in the salivary glands of patients with

Sjogren’s syndrome 24 and the synovia or inflamed muscle tissue/skin of people afflicted with rheumatoid arthritis 25, 26 or dermatomyositis 27, 28, respectively. pDC are over-represented in 3-oxoacyl-(acyl-carrier-protein) reductase the blood of patients with type I diabetes around the time of onset 29. pDC also infiltrate tumors 30–37 and are recruited to infected sites during viral infections caused by herpes zoster virus 38, HCV 39 and herpes simplex virus 40. The accumulation of pDC has been observed in many animal models of disease. During influenza 41–43 and RSV 44, 45 infections, pDC are recruited to the lungs and draining LN of mice. pDC numbers increase in the pancreatic LN around the onset of diabetes in NOD mice 46 and in the pancreas during lymphocytic choriomeningitis virus infection 47. In mouse models of HSV infection, pDC accumulate in the LN following footpad infection with HSV-1 48 and in the vaginal mucosa during HSV-2 infection 49. pDC are also recruited to the vaginal mucosa of rhesus macaques intravaginally infected with SIV 50. Furthermore, it has been reported that pDC infiltrate LN during SIV infection 51, 52.

One of the most comprehensive studies of this phenomenon to date was conducted using the rodent malaria parasite Plasmodium chabaudi chabaudi, for which it was shown that the major genetic determinant of the strain-specificity of the immunity achieved via immunization with blood-stage parasites is the merozoite surface protein

1 gene (msp1) (3). Natural malaria infections of both rodents and humans are initiated by the bite of malaria parasite-infected Anopheles see more mosquitoes, which inoculate sporozoites into the skin during blood feeding. Very effective protective immunity against malaria can be achieved by immunization with sporozoites that have been attenuated by irradiation (4). More recently, other methods of sporozoite attenuation such as genetic modification (5) and chemical attenuation (6) have also been shown to confer protective immunity against re-infection. A similar approach in which live sporozoites are inoculated contemporaneously with anti-erythrocytic stage drugs such as chloroquine (CQ) has recently been shown to confer sterile protective immunity against Plasmodium falciparum in human volunteers CHIR-99021 cell line (7).

The protective efficacies of these vaccine strategies have, most commonly, been assessed using parasites homologous to the vaccinating strain. Those few studies which have assessed the level of protection against heterologous challenge have almost exclusively assessed the degree of cross-protection between malaria parasite species (8–15) and are generally inconsistent

see more in their conclusions. Should it occur, parasite strain-specificity to the induction of immunity by live sporozoites of P. falciparum will need to be understood if such vaccination is to be used effectively. Here, we present the results of experiments to test for and determine the degree of cross protection between strains of Plasmodium chabaudi immunized by inoculation of live sporozoites in conjunction with mefloquine (MF) treatment. All experiments were carried out in compliance with the British Home Office Animals (Scientific Procedures) Act 1986. For sporozoite immunizations, two groups of 20 inbred female CBA/Ca mice (6 weeks old at the time of first immunization) were inoculated via intraperitoneal (IP) injection with known numbers of sporozoites of P. c. chabaudi clones AJ or CB diluted in a 50 : 50 mixture of Foetal Calf Serum (FCS) and Ringer’s solution contemporaneously with oral MF treatment (20 mg/kg/day for 5 days). Immunizations were performed twice with an interval of 3 weeks between inoculations. Each mouse received an inoculation of ∼400 sporozoites of each strain in the first immunization, and ∼2000 in the second. Twenty control mice were inoculated with 50 : 50 FCS: Ringer’s solution only, and also drug treated. Five weeks following the second immunization, mice were each challenged IP with 2400 sporozoites of either strain, or with 1 × 106 parasite-infected red blood cells (iRBCs).

73 m2) were excluded. Histopathological findings in renal biopsies specimen, including global glomerulosclerosis (GGS), segmental glomerulosclerosis (SGS), CG, interstitial fibrosis / tubular atrophy (IF/TA), intimal thickening of arteries, arteriolar hyalinosis, glomerular density (GD; glomerular number per renal cortical area)

and mean glomerular volume (GV), were evaluated. These histopathological finding in HNS patients with mild (<1 g/day) and overt (≥1 g/day) proteinuria were compared with those in the biopsy specimens from kidney transplant donors (KTD) as healthy controls. Results: The GD of HNS patients with mild and overt proteinuria was significantly lower than that from KTD. Of note, the GD of HNS Temsirolimus patients with overt proteinuria was significantly lower than those of HNS patients with mild proteinuria. These differences remained significant when GGS were included in the calculation of the GD. Other histopathological parameters, including the severity of GGS, SGS, CS, IF/TA, artery and arteriole lesions did not differ between these HNS groups. Both of the GV in HNS patients with mild proteinuria and those with overt proteinuria were significantly larger than that of KTD. Conclusions: These results suggest that a low GD

is a renal histological feature of HNS patients with overt proteinuria. SJA’BANI MOCHAMMAD1,2,3,4, IRIJANTO FREDIE1, PRASANTO HERU1, BAWAZIER LUCKY AZIZA2, ZULAELA ZULAELA3, HARSOYO SAPTO1, TOMINO YASUHIKO4 1Internal

Medicine, Erastin order Faculty of Medicine, Gadjah EPZ 6438 Mada University; 2Internal Medicine, University of Indonesia, Jakarta; 3Mathematics and Natural Sciences, Gadjah Mada University; 4Juntendo University, Division of Nephrology, Faculty of Medicine, Tokyo Introduction: Soursop (guanabana /Annona muricata L.) is an exotic fruit prized for its very pleasant, sub-acid, aromatic and juicy flesh. Soursop fruit tissue is known for its acidic pH and high level of polysaccharides, polyphenolic, citric acid, secondary metabolites, with anti-inflamation, vasodilatation. The result of a case study reported that soursop juice consumption could reduce uric acid serum. This study is to determine the efficacy of soursop consumption twice 100 g/day in decreasing uric acid, urea, creatinine in sera, and blood pressure. Method: Pre and Stage 1 hypertension Kidney disease patients with high serum uric acid (≥7.9 mg/dl were asked to consume a 100 gram supplement of soursop juice a day for eight weeks, conducted before and after study design and without changing the anti-hypertensive drug. The study was followed by an evaluation of the uric acid, creatinine, urea in sera and blood pressure level every two weeks. Result: Seventeen out of twenty patients followed this study for eight weeks. The baseline serum uric acid level was 8.41 ± 0.87 mg/dl to 7.48 ± 0.50 mg/dl in eight weeks with p value <0.05. The serum Creatinine level was decreased from 1.82 ± 1.

The flap was then covered by skin graft. The reconstruction had shown good early results with complete survival of the flap, as well as good functional CYC202 cost and esthetic outcome at six months. The greater

omentum can therefore be used as a free flap for scrotal reconstruction. It allows easy prefabrication and flap inset. The deep inferior epigastric vessels are also suitable recipient vessels. © 2010 Wiley-Liss, Inc. Microsurgery 30:410–413, 2010. “
“Multiple reconstructions of the hepatic arteries (HA) after cancer resection presents a surgical challenge, not only because it is technically demanding, but also because attention must be paid to potential ischemic injury to the liver caused by the prolonged ischemia. We present a novel “preexcisional artery reconstruction” method for minimizing ischemic injury of the liver. A Dorsomorphin clinical trial 65-year-old woman presented

with cholangiocarcinoma invading the HA. Pancreatoduodenectomy, resection, and multiple reconstruction of the HA were performed. First, the left hepatic artery (LHA) was reconstructed prior to the tumor resection. During this procedure, blood supply was maintained to most of the liver via the right hepatic artery (RHA). Then, resection of the tumor en bloc with the HA was performed, followed by reconstruction of the RHA. During this procedure, blood supply was maintained via the already-reconstructed LHA, thereby limiting the ischemic area. Use of this method allowed the ischemia time and region to be divided and minimized, thereby leading to a reduced risk of ischemia-related complications. We believe that this method may be one of the useful approaches in multiple HA reconstruction. © 2012 G protein-coupled receptor kinase Wiley Periodicals, Inc. Microsurgery, 2012. “
“Rib-sparing internal mammary

vessel (IMV) exposure in breast reconstruction is becoming common, with a smaller space in which to perform the microanastomoses. The objectives were to determine whether patient height could be used as a proxy measurement for intercostal distance (ICD), assess whether the complication rate or the flap ischemia time are affected in such surgery, and provide anatomical data about ICDs. Data were collected from 95 consecutive patients (109 breasts) undergoing free flap breast reconstruction using rib-sparing vessel exposure over a 3-year period by one surgeon. Pearson’s product moment correlation coefficient was used to assess the relation between height and ICD, body mass index (BMI), operative times, and flap outcomes. There was no correlation between patient height and ICD (r = 0.087), age, BMI, recipient vessel preparation time, and flap ischemia time. Being able to predict patients with a small ICD in whom microsurgery may be more challenging can influence surgical planning. The anatomy of the intercostal spaces is variable and was not predictable in relation to height, BMI, or age.

Moreover, reticulocytes infected with R428 order Plasmodium yoelii released exosomes capable of activating a protective anti-malaria immune response in naïve mice in an adjuvant-independent

manner [39]. Our present data, demonstrating the protective efficacy of exosomes in controlling an M. tuberculosis infection, supports the potential application for this type of cell-free vaccine. Unexpectedly, we did not see much protection with the BCG 9 months after vaccination. Examination of the data suggests that the BCG-vaccinated mice showed only a slightly lower CFU compared to unvaccinated mice (i.e. PBS control versus BCG, or BCG plus exosomes from untreated macrophages). However, the 0.3 log drop in spleen CFU between BCG-vaccinated and nonvaccinated mice was statistically significant. In a number of published studies, there was

protection by the initial BCG vaccination even in the absences of a booster vaccine. In most of these studies, a shorter window between BCG vaccination and boosting was used [40, 41]. Nevertheless, in some studies where protection with the primary BCG vaccination was observed, the intervals between BCG vaccination and M. tuberculosis infection were on the same https://www.selleckchem.com/products/Fulvestrant.html timeframe as in our study [42]. Interestingly, in the study by Dietrich et al. a similar ∼0.3 log drop in spleen CFU was observed when comparing unvaccinated mice to those vaccinated with BCG 8 months prior to M. tuberculosis infection [42]. These results suggest that in some cases, the protection may be minimal Anacetrapib after a long interval between vaccination and infection. The incomplete protection we observed is likely due to limited antigen-specific memory T cells available for reactivation 9 months after the initial BCG vaccination (see Fig. 7). It is unclear

why we see this limited immune/protective response but one hypothesis is that our BCG strain failed to survive in vivo for the time necessary to induce a potent long-term memory response. Previous studies of BCG-vaccinated mice treated with antibiotics suggest that viable BCG is required for vaccine efficacy [43]. For most individuals, M. tuberculosis infection induces a protective TH1-mediated immune response characterized by the development of antigen-specific CD4+ and CD8+ lymphocytes producing IFN-γ and other TH1-type cytokines [28]. During the subunit vaccine studies, it was evident that the control of an M. tuberculosis infection required an adjuvant that induces a robust TH1 but limited TH2 immune response [44, 45]. It has been demonstrated that exosomes carrying parasitic or tumor antigens could generate a strong antigen-specific TH1 immune responses resulting in control of the parasitic infection or in limiting tumor progression [29-31]. Our previous studies indicated that exosomes released from M.

Briefly, after partial tracheal resection under deep anaesthesia, a 22-gauge catheter was inserted into the choana towards the heads of a portion of mice. Each nasal cavity was gently irrigated by l ml of sterile saline. Nasal lavage fluid (NLF) was collected and centrifuged, and the supernatant was stored at −20 °C for cytokines analysis using enzyme-linked immunosorbent assay (ELISA). Cytokine levels of IL-5, Maraviroc IL-10,

IL-17, TGF-β1, IFN-γ and endogenous LF in NLF were measured by ELISA according to the manufacturers’ instructions (Boster Biotech, Wuhan, China). The detection sensitivity of the ELISA kits was <2 pg/ml for all cytokines. Five mice per group were chosen for histopathology. Animals were decapitated

and the heads were decalcified, embedded in paraffin and sectioned as previously described [22]. Histological changes in the nasal mucosa of all groups were examined using haematoxylin-eosin (HE) staining for eosinophils and periodic acid-schiff stain (PAS) for goblet cells. The cytoplasm of eosinophils in the nasal lamina propria (LP) stains red by HE, while the cytoplasm of goblet cells from the epithelium stains purple by PAS. Eosinophils in the LP were counted in four different fields, and eosinophil frequencies were expressed as cells/mm2. Goblet cells were expressed as cells/mm of epithelium. Th1, Th2, Th17 and Treg cell transcription factor and cytokine mRNA expression levels were determined each group (n = 5 per group). Nasal mucosa from samples was obtained using toothed microscopic tweezers under a stereo microscope (ZAS301; Beijing, China) and immediately frozen at −70 °C. Total selleck kinase inhibitor RNA was extracted by Trizol (Invitrogen, Carlsbad, CA, USA), and 0.5 μg total RNA was used for the reverse transcription reaction using

a Rever Tra Ace qPCR RT Kit (TOYOBO, Osaka, Japan) according to the manufacturer’s instructions and as previously described [4]. The qPCR of T-bet (NM_019507.2), GATA-3 (NM_008091.3), ROR-C (NM_011281.2), FOXP3 (NM_001199348.1), IFN-γ (NM_008337.3), IL-5 (NM_010558.1), IL-17 (NM_010552.3), IL-10 (NM_010548.2), TGF-β1 (NM_011577.1), TNF-α (NM_013693.2) and LF (NM_008522.3) was performed with an ABI 7500 real-time PCR system (Applied Biosystems, Rucaparib Foster City, CA, USA) using the SYBR qPCR mix (TOYOBO) according to the manufacturer’s protocol. Briefly, 1.0 μl cDNA was added to 10 μl SYBR qPCR mix, 7 μl RNase-free water and 1 μl of each primer (10 μm). The PCR conditions consisted of an initial denaturation at 95 °C for 50 s, followed by amplification for 40 cycles of 15 s at 95 °C, 15 s at 56–60 °C (varying between primer sets) and 50 s at 72 °C. An analysis of relative gene expression was calculated using the 2−ΔΔCT method on the ABI 7500 Sequence Detection System Software (Applied Biosystems). Gene expression was normalized to glyceraldehydes-3-phosphate dehydrogenase (GAPDH, NM_008084.2).

It was therefore AZD2281 solubility dmso expected that Treg cells pre-incubated with RBV could not induce the conversion of CD4+ CD25− FOXP3− T cells into CD4+ CD25+ FOXP3+ T cells. To confirm this hypothesis, we compared FOXP3 expression in CD4+ CD25− T cells stimulated with either CD4+ CD25+ CD127− T cells or those pre-incubated with RBV. FOXP3 was rarely expressed in CD4+ CD25− T cells when they were stimulated alone (Fig. 3a, upper left), and RBV had little effect on the expression of FOXP3 in either CD4+ CD25− (Fig. 3a, upper right) or CD4+ CD25+ CD127− T cells (Fig. 3a, centre right and left) after stimulation. CD25+ FOXP3+ cells increased when CD4+ CD25− T cells

were stimulated with CD4+ CD25+ CD127− T cells (Fig. 3a, lower left). Surprisingly, these double-positive cells were markedly decreased when CD4+ CD25− T cells were stimulated with CD4+ CD25+ CD127− T cells pre-incubated with RBV (Fig. 3a, lower right). Mean numbers of CD25+ FOXP3+ cells were markedly reduced when CD4+ CD25− T cells were incubated with RBV-pre-incubated CD4+ CD25+ CD127− T cells, and the inhibition rate was 54·394 ± 11·975% (Fig. 3b). To confirm whether CD4+ CD25− T cells are activated or remain at rest in the presence of RBV, we also analysed the relationship between down-modulation

of FOXP3 and the expression of the two buy R788 CD45 isoforms CD45RA and CD45RO. Although the percentage of FOXP3+ CD45RO+ T cells was increased when CD4+ CD25− T cells were incubated with CD4+ CD25+ CD127− T cells, it was markedly decreased when CD4+ CD25− T cells were incubated with RBV-pre-incubated CD4+ CD25+ CD127− Cell press T cells without any decrease in the

total counts of CD45RO+ cells (Fig. 3c). To confirm the inhibitory activity of CD4+ CD25− T cells incubated with CD4+ CD25+ CD127− T cells pre-incubated with 0 or 500 ng/ml of RBV, whole cells including CD4+ CD25− and CD4+ CD25+ CD127− T cells or those pre-incubated with RBV after a 7-day stimulation were mixed with freshly isolated CD4+ CD25− T cells and re-stimulated for 7 days with 0·05 μg/μl of anti-human CD3 mAb in the presence of irradiated allogeneic PBMCs. The cell viability rate of the collected cells after a 7-day incubation were 80–90%. Percentages of CD25+ CD127− T cells in these two cultures were markedly low (Fig. 4a, two left panels) and those of CD25+ FOXP3+ T cells did not change when CD25+ CD127− T cells were pre-treated with RBV (Fig. 4a, two right panels). The thymidine incorporation assay indicated that CD4+ CD25− T cells incubated with RBV-pulsed or unpulsed CD4+ CD25+ CD127− T cells inhibited the freshly isolated CD4+ CD25− T cells (Fig. 4b). Because human Treg cells exhibit inhibitory activity in a contact-dependent and contact-independent fashion, it was important to determine whether RBV inhibited either or both of these cell types.

The

authors summarize the current state of knowledge within each topic, and highlight emerging questions that will stimulate future investigations. Osol and Moore [12] introduce the topic by discussing the broad series of hemodynamic changes that occur during pregnancy, and the types of structural adaptations that are observed in each of the branches of the uterine vasculature. Ku-0059436 price The authors propose a conceptual framework for understanding the regulation of uterine vascular remodeling. They synthesize present knowledge of the temporal and spatial sequences of events, highlighting the relative roles of local versus systemic factors and hemodynamics as driving forces for the remodeling processes. Attention is given to the challenges of applying information gained from animal models to the human condition, by considering the extent of variation in these processes across species, and from one individual to another in humans. In considering the mechanisms regulating uterine vascular remodeling, evidence for the role of endocrine factors, such as estrogen, in modifying the local responses to hemodynamic cues is discussed.

The dependence of the remodeling events on the appropriate function of nitric oxide synthase 3 raises the question of how these critical structural adaptations are altered in pregnancy states that are known to involve endothelial cell dysfunction (i.e., preeclampsia; intrauterine growth restriction). One of the difficulties in assessing the fetoplacental circulation is the limited capacity to visualize the three-dimensional Z-VAD-FMK mouse structural organization of the fetoplacental vascular network. Micro-computed tomography (micro-CT) imaging can be exploited as a tool for this purpose. Rennie et al. [13] discuss this

emerging area of investigation, balancing the strengths and limitations inherent to the micro-CT imaging technique. The authors demonstrate the power of this technique to quantify physiological parameters such as pressure distributions and arterial resistance within a vascular bed as a whole, Ureohydrolase as well as within individual vessel segments. Micro-CT imaging at specific stages of development enables a detailed analysis of the temporal development and adaptation of the fetoplacental vasculature. Use of various mouse strains provides the opportunity to map the development of divergent vascular networks to the functions of specific genes. The authors illustrate how micro-CT imaging may be applied to examine the impact of environmental factors, genes, as well as the interplay between the two, on the development of the fetoplacental vasculature. In addition to the structural adaptations within the fetoplacental circulation, vascular tone plays a key role in determining fetoplacental blood flow.