Inflammatory cytokines facilitate neurotoxicity by encouraging excitotoxicity and the inflammatory response, but simultaneously they facilitate the neurotrophic mechanisms and induction of cell growth see more factors which are neuroprotective [13]. It has also been shown by Vuylsteke et al that there is an increased gradient of inflammatory marker IL-8 in the brain after cardiopulmonary bypass, which is attenuated

by hypothermia [14]. This gradient continued into the postoperative period. The primary insult also results in an immediate disturbance of the cerebral circulation, resulting in cerebral ischaemia and which contributes significantly to about 90% of deaths after closed head injuries. [15]. Ischaemic brain damage is perpetuated by factors such as hypotension, hypoxia, raised intracranial pressure, oedema, focal tissue compression, damage to microvasculature, and in late phases, vasospasm in the remaining vessels [16, 17]. The time sequence after TBI can be arbitrarily divided into an early

(phase 1, immediate, with hypoperfusion), intermediate (phase 2, on days 1–3, when hyperaemia can be seen) and a late vasospastic phase (phase 3, on days 4–15, with a marked reduction in blood flow) [17]. These different phases are associated with marked regional variations in cerebral blood flow, with a reduction in blood flow to the surrounding of the ischaemic core, which does not respond to augmentation of cerebral perfusion pressure [18]. Surviving apoptosis Programmed cell death (which is often referred to as apoptosis selleck chemicals although strictly speaking this refers to the distinct morphological changes after programmed cell death) is a genetic mechanism by which cells are eliminated during development, and is the physiological mechanism by which cells are normally removed in the adult animal [19]. This involves specific genes and proteins which were first described in neuronal development

of the round worm [20]. Following TBI there is increased expression of two main sets of genes which are genes encoding for the caspase family of cysteine proteases [including interleukin-1β converting enzyme (ICE) and cpp32] and a family of genes that are next homologous to the oncogene Bcl-2 that either promote or suppress cell death. The Bcl-2 gene family controls both caspase dependent and independent apoptosis. [19, 21–23]. The endpoint of all these steps is fragmentation of cellular DNA with collapse of the nuclear structure, followed by the formation of membrane-wrapped apoptotic bodies, cleared by macrophages [24]. Apoptosis is now recognised as an important factor in secondary brain injury [25]. Following TBI, two different types of cells are visible; type 1 and 2 cells. The type 1 cells show a classic necrotic pattern (this follows the primary brain injury) and type 2 cells shows a classic apoptotic pattern on microscopy [25, 19]. Cells undergoing apoptosis die without membrane rupture and therefore elicit less inflammatory reactions.

References 1. Ohgaki H, Kleihues P: Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial find more gliomas. J Neuropathol Exp Neurol 2005,64(6):479–489.PubMed 2. DeAngelis LM: Brain tumors. N Engl J Med 2001,344(2):114–123.PubMedCrossRef 3. Sanai N, Alvarez-Buylla A, Berger MS: Neural stem cells and the origin of gliomas. N Engl J Med 2005,353(8):811–822.PubMedCrossRef 4. Singh RP, Gu M, Agarwal R: Silibinin inhibits colorectal cancer growth by inhibiting tumor cell proliferation

and angiogenesis. Cancer Res 2008,68(6):2043–2050.PubMedCrossRef 5. Singh RP, Mallikarjuna GU, Sharma G, Dhanalakshmi S, Tyagi AK, Chan DC, Agarwal C, Agarwal Selleck Inhibitor Library R: Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting nuclear factor kappaB-mediated inducible chemoresistance. Clin Cancer Res 2004,10(24):8641–8647.PubMedCrossRef 6. Ramasamy K, Agarwal R: Multitargeted therapy of cancer by silymarin. Cancer Lett 2008, 269(352–362.

7. Kaur M, Agarwal R: Silymarin and epithelial cancer chemoprevention: how close we are to bedside? Toxicol Appl Pharmacol 2007,224(3):350–359.PubMedCrossRef 8. Kim KW, Choi CH, Kim TH, Kwon CH, Woo JS, Kim YK: Silibinin inhibits glioma cell proliferation via Ca2+/ROS/MAPK-dependent mechanism in vitro and glioma tumor growth in vivo. Neurochem Res 2009,34(8):1479–1490.PubMedCrossRef 9. Denizot F, Lang R: Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986,89(2):271–277.PubMedCrossRef

10. Pastorino JG, Chen ST, Tafani M, Snyder JW, Farber JL: The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition. J Biol Chem 1998,273(13):7770–7775.PubMedCrossRef 11. Orrenius S, Zhivotovsky B, Nicotera P: Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 2003,4(7):552–565.PubMedCrossRef 12. Huang Y, Wang KK: Calpain The calpain family and human disease. Trends Mol Med 2001,7(8):355–362.PubMedCrossRef 13. Vanags DM, Porn-Ares MI, Coppola S, Burgess DH, Orrenius S: Protease involvement in fodrin cleavage and phosphatidylserine exposure in apoptosis. J Biol Chem 1996,271(49):31075–31085.PubMedCrossRef 14. Koivunen J, Aaltonen V, Peltonen J: Protein kinase C (PKC) family in cancer progression. Cancer Lett 2006,235(1):1–10.PubMedCrossRef 15. Musashi M, Ota S, Shiroshita N: The role of protein kinase C isoforms in cell proliferation and apoptosis. Int J Hematol 2000,72(1):12–19.PubMed 16. Gutcher I, Webb PR, Anderson NG: The isoform-specific regulation of apoptosis by protein kinase C. Cell Mol Life Sci 2003,60(6):1061–1070.PubMed 17.

In the present work, we compared C. parapsilosis bloodstream isolates and strains recovered from the hospital setting regarding their virulence in vitro. Mononuclear phagocytes were used

to test the strain ability to: (i) induce cytotocixity; (ii) activate TNF-α release; (iii) filament in vitro, both during macrophage infection and in the presence of serum, and (iv) secrete hydrolytic enzymes. Candida parapsilosis environmental isolates revealed to be the most virulent to macrophage cells, being potentially more deleterious, particularly in the initial phases of the infection, than strains from a clinical Akt targets source. Results Candida parapsilosis interaction with macrophages The ability of macrophages to kill C. parapsilosis bloodstream isolates and environmental

strains was determined by CFU counting after one hour co-incubation, using six isolates of each. The average percentage of yeast killing for the environmental isolates was 10.97 ± 2.67 while for clinical isolates it was 33.22 ± 5.25, the difference being statistically significant (p = 0.0409). The interaction of one clinical and one environmental isolate with macrophages was followed for 12 hours of incubation. Microscopic examination showed that the clinical selleck products isolate was able to produce pseudo-hyphae and maintained that ability in contact with macrophages (Figure 1a and 1b), while the environmental isolate kept the yeast unicellular morphology (Figure 1c to 1e). Figure 1 Microscopic observations of C. parapsilosis incubated with J774 macrophages. Hemacolor staining and bright field images of the co-incubation of macrophages with the clinical isolate 972697

(a and b) and the environmental isolate CarcC (c to e), after 12 hours. Arrows point to the different yeast morphologies in contact with macrophages. Miconazole The percentage of dead macrophages after co-incubation with the same two isolates, assessed by propidium iodide (PI) staining, showed that macrophage killing did not vary significantly in the first 8 hours of incubation, with percentages of macrophage death similar to the negative control (Figure 2 and 3). However, after 12 hours of infection with the clinical isolate the percentage of macrophage killing increased to 41% (Figure 2c, 12 h). On the contrary, after 12 hours co-incubation with the environmental strain, the number of macrophages in the slide was significantly reduced (Figure 3a, b, 12 h) when compared with the first hours of infection, and with the negative control (Figure 3d, 12 h) and many yeast cells could be observed. Therefore, in this case, the proportion of PI positive cells could not be quantified due to the reduction of macrophage cell numbers, probably by cell lysis. Together, these observations suggested that clinical and environmental isolates behave differently in contact with macrophages.

βA is a non-proteinogenic amino acid that is synthesized in the liver as the final metabolite of uracil and thymine degradation. While produced endogenously, the primary source of βA in humans comes from their diet. Meat is the primary source of dietary βA, with highest concentrations found in chicken and turkey [11]. The performance enhancing potential of βA supplementation lies in its effect on increasing muscle carnosine levels [4, 7, 8, 12] due to its role as the limiting factor in the muscle carnosine synthesis [12–14]. Carnosine (β-alanyl-L-histidine) is a dipeptide found in muscle tissue that acts as an intramuscular buffer of [H+] [4, 7, 8, 12]. During high intensity exercise, a greater reliance

on the glycolysis and phosphagen systems to supply ATP to working muscles results in an accumulation of [H+] which leads to exercise-induced metabolic acidosis [15]. A decline in pH has been implicated as Compound Library cell assay a cause of muscle fatigue and decreased muscle contractile function [16]. Attenuating exercise induced acidosis is purported to result in performance improvements in activities requiring prolonged bouts of high intensity work. This is supported by findings that muscle carnosine concentrations are higher in sprinters [17], bodybuilders [18], and team sport

athletes regularly participating in high intensity intermittent exercise [19, 20] than in their sedentary counterparts. Previous studies investigating Inhibitor Library the effect of βA on performance measures have shown improvements in total work done (TWD) [4, 10], time to exhaustion (TTE) [1, 4, 10], physical working capacity at fatigue threshold (PWCFT) [1, 3], power output at lactate threshold (LT) [5], attenuated fatigue during repeated bouts of resistance training [7], and final 30 second sprint performance during a 2 hour time trial [9]. Research has however been conducted using primarily cycle ergometry

[1–5, 9, Oxalosuccinic acid 10], so it remains to be determined if βA supplementation would have an ergogenic effect during running performance. Therefore, we hypothesized that βA supplementation would delay OBLA. Therefore, the purpose of this study was to determine the effects of 4 weeks of βA supplementation on HR@OBLA, %HRmax@OBLA, %VO2max@OBLA, VO2max during incremental treadmill running. Methods Subjects Seventeen men who were recreationally active and running at least 3 times per week and had not taken any sports supplements for at least 6 weeks volunteered to participate in this study (Table 1). Subjects provided signed consent to participate and all study procedures were approved by the Northern Illinois University Institutional review board prior to enrollment in the study. Table 1 Physical Characteristics of Subjects. Variable βA (n = 8) PL (n = 9) Age (yr) 24.9 ± 5.1 24.9 ± 4.3 Height (cm) 181.4 ± 9.9 179.8 ± 7.9 Body Mass (kg) 77.9 ± 9.0 80.6 ± 9.1 BMI 23.7 ± 2.3 24.9 ± 1.

melitensis grown in rich culture medium [10] or under stress conditions [11], of the cell envelope of B. abortus[12], and, more recently, of B. suis during macrophage infection and under oxygen depletion [13, 14] and of B. abortus in macrophages [15]. In addition, viable brucellae are able to persist in the environment, and periods learn more of survival in soil, manure and water have been determined, reaching up to 180, 240,

and 150 days, respectively [16]. Soil may even be the natural habitat of the lately described species B. microti[17]. The aim of our study is to better understand and characterize the adaptation of B. suis to extreme nutrient starvation as it may occur under specific conditions of persistence during the infection of the host, using a well-described model. A quantitative proteome analysis comparing the protein profiles of brucellae under starvation with those cultured in rich medium was performed. Results and discussion Survival of B. suis under extreme starvation conditions Based on early work performed on M. tuberculosis[8], we have developed a simple nutrition starvation model to study the impact on long-term viability of the pathogen. Following growth in rich medium, bacteria were incubated in a salt solution devoid of carbon and nitrogen

sources under shaking and aeration. Oxygen concentration was kept constant in order to avoid variation of a second parameter. A sharp decline of CBL-0137 in vivo approximately Cyclooxygenase (COX) 2.5 logs was observed over a period of 2 weeks, followed by stabilisation of the number of viable bacteria during the next 4 weeks (Figure 1). The colony formation on TS solid medium of bacteria sampled from the salt solution for enumeration of viable bacteria confirmed that these maintained their capacity to grow in rich medium. Additional experiments performed under the same conditions but over a period of 27 weeks showed that stable concentrations of viable brucellae were obtained throughout a period of more than 6 months (data not shown). This behaviour indicated the adaptation of a subpopulation

of the pathogen to the environmental conditions encountered. The growth curves of B. suis under nutrient starvation are similar to those of Mycobacterium sp. [8, 18, 19]. Both, long-term survival of a “starvation-resistant” subpopulation and an equilibrium between dying bacteria and those replicating while feeding on nutrients released by dead brucellae, have to be taken into consideration. Washing of the bacteria and replacement of medium after three weeks of incubation, however, did not alter the survival kinetics (Figure 1, red curve), indicating that soluble metabolites originating from dead bacteria may play, at best, a minor role. The lack of net replication of B. suis is an indirect proof of extreme starvation and indicates the set-up of a state of persistence. Figure 1 Survival kinetics of Brucella under starvation conditions.

The number in parentheses indicates the amplicon length in bp (Figure 5 B). Subjects in the figure are not in scale. Our second objective was to remedy a drawback of PCR’s inability to distinguish signals originated from live or dead cells, by combining the qPCR with PMA treatment. Recently, PMA has been used for differentiation of live cells in qPCR [16, 19–21, 24, 32, 34, 37, 38] However, several studies revealed that the inhibition of amplification of DNA of dead cells was incomplete [22, 23, 37, 39]. In order to improve the efficacy of PMA buy NVP-HSP990 treatment, we evaluated the effect of amplicon length

on PMA-mediated inhibition of DNA amplification from dead cells by qPCR (Table 1). We found efficacy of PMA treatment appeared

to be well correlated to the amplicon length, which is in good agreement with the previous finding [23]. However, our results showed significant differences with their conclusion on efficiency of amplicon length, i.e. PMA-mediated suppression of DNA amplification from dead cells was incomplete with amplicons shorter than 190 bp [23]. With amplicon D (130 bp), we were able to achieve a C T value difference of 13.1 between the treated and untreated dead cells (Table 1). Although amplicon E (260 bp) generated a bigger C T value difference (15.44), the C T value for DNA of untreated dead cells increased from 18.34 to 21.19, reflecting about a 3-C T -value decrease in sensitivity of the PMA-qPCR assay (Table 1). Vorinostat price check details This finding is of importance because it can give guidance for selection of primer pairs for the development of qPMA-PCR assays. There are no good theoretical explanations for this “amplicon length effect” associated with PMA treatment. It may be related to the mechanism of the PMA-treatment. When dead cells are treated with PMA, the DNA is blocked by covalent bonds and thus it cannot be amplified in PCR [38]. It could be understood that the larger an amplicon is, the longer the region that the polymerase needs to cover, the higher probability for the target DNA being blocked by a covalent bond (s). On the other hand, if the amplicon length is too

long (over 200 bp), the sensitivity of the qPCR will be compromised, resulting in lower sensitivity of the assay. This finding has significance to future designs of qPCR assay in general. Consumption of fresh produce including salads, lettuce, juice, melon, sprouts, and berries has been identified as important sources for Salmonella outbreaks [40]. It is important to accurately monitor live cells in food samples, because only live bacteria can cause disease [16]. We applied PMA-qPCR technology to selectively detect low numbers of live Salmonella cells in spiked spinach samples. This PMA-qPCR assay positively detected Salmonella in spinach spiked with 30 CFU/g at 4-h enrichment or from samples inoculated with 3 × 103 CFU/g without enrichment (Figure 3A).

Am J Physiol 1990, 259:F318-F324.PubMed 69. Patrono C, Dunn MJ: The clinical significance of inhibition of renal

prostaglandin synthesis. Kidney Int 1987, 32:1–10.PubMedCrossRef 70. Kemmler W, von Stengel S, Köckritz C, Mayhew J, Wassermann A, Zapf J: Effect of compression stockings on running performance in men runners. J Strength Cond Res 2009, 23:101–105.PubMedCrossRef 71. Knechtle B, Knechtle P, Rüst CA, Gnädinger M, Imoberdorf R, Kohler G, Rosemann T, Ballmer P: Regulation GSK126 of Electrolyte and Fluid Metabolism in Multi-stage Ultra-Marathoners. Horm Metab Res 2012. Epub ahead of print. 72. Rüst CA, Knechtle B, Knechtle P, Rosemann T: Higher prevalence of exercise-associated hyponatremia in Triple Iron ultra-triathletes than reported for Ironman triathletes. Chin J Physiol 2012, 55:147–155.PubMed 73. Butner KL, Creamer KW, Nickols-Richardson SM, Clark SF, Ramp WK, Herbert WG: Fat and muscle indices assessed by pQCT: relationships with physical activity and type 2 diabetes risk. J Clin Densitom 2012. Epub ahead of print. Competing interests The authors Seliciclib mouse declare that they have no competing interests. Authors’ contributions MM drafted and wrote the manuscript. BK designed the study and assisted the manuscript preparation. BK, JB, PK, CM, AM and BE conducted all the measurements during two field

study for data collection before and after the race. CAR and TR assisted in data analyses, statistical analyses, data interpretation and manuscript preparation. All authors have read and approved the final version of the manuscript.”
“Introduction Carnosine (β-alanyl-L-histidine) is a naturally occurring dipeptide found in high concentrations in skeletal muscle [1] and due to its pKa (6.83), it is a suitable buffer over the exercise intramuscular

pH transit-range [2]. β-alanine supplementation has been shown to be effective in increasing muscle carnosine levels [1], thereby increasing muscle buffering capacity, with the potential to improve exercise performance and capacity that is limited by the accumulation of hydrogen ions (H+) [3, 4]. Recent research has focussed on repeated sprint ability, a key component of team sport performance Fluorometholone Acetate [5], due to its association with H+ buffering capacity in both professional and amateur footballers [6]. Despite this, research has shown no effect of β-alanine supplementation on repeated sprint performance alone [7, 8], or repeated sprints performed during simulated games play [9]. However, these protocols measure high-intensity exercise performance of less than 60 s in duration and, in a meta-analysis of the literature, Hobson et al. [10] showed that β-alanine was most effective in improving exercise capacity during exercise lasting in excess of 60 s. Therefore, β-alanine supplementation may be more effective in increasing sport specific high-intensity intermittent exercise capacity.

Conversely, we expected genes whose expression was associated with good prognosis to generally be highly expressed

in patients who survived and to be expressed at low levels in those patients who succumbed. Therefore, the ranking of the genes was performed as follows for genes predictive of poor or good prognosis. Genes predictive of poor prognosis i) A predictive score for each gene was computed for each gene across all patients, and was initially set at 0.   ii) 1. The score for each gene was increased by 1 when the patient had both high gene expression and died, or had both low gene expression and survived.   2. The score was decreased by 1 when the patient had both low CP673451 cell line gene expression and died, or had both high gene expression and survived.   3. Average gene expression levels did not lead to any changes in the predictive score.     Genes predictive of good prognosis i) A predictive score for each gene is computed for each gene across all patients, and was initially set at 0.   ii) 1. The score was increased by 1 when the patient had both high gene expression and survived, or had both low gene expression

and died.   2. The score is decreased by 1 when the patient had both low gene expression and survived, or had both high gene Captisol solubility dmso expression and died.   3. Average gene expression levels did not lead to any changes in the predictive score.     We then combined the top ranked genes from both the Amisulpride poor-prognosis and good-prognosis gene lists to generate a predictor gene signature. We completed all of the steps described above using Microsoft Excel™ 2007. Template file available upon request. Measuring the predictive ability of the gene signature In order to separate the training data set into good prognosis and poor prognosis groups we summed the expression of both poor-prognosis genes (poor-prognosis gene score) and good-prognosis genes (good-prognosis gene score) for all the patients in our training set. To give each patient a single overall-prognosis score we subtracted the good-prognosis gene score from the poor-prognosis

gene score, and ranked the patients according to this new total. This led patients with the highest and lowest expression of poor-prognosis and good-prognosis genes, respectively, to receive the highest scores, and patients with the lowest and highest expression of poor-prognosis and good-prognosis genes, respectively, to receive the lowest scores. In this fashion, high scores were indicative of poor prognosis and low scores were indicative of good prognosis. In order to determine a optimal cut-off score which would yield prognosis predictions with the highest possible specificity and sensitivity, we used receiver-operator characteristic curves (ROC) [6]. This generated a list of possible cut-off scores, as well as each score’s associated specificity and sensitivity.

This observation indicates that caspase activation is not directly related to HCV mediated damage and suggests the involvement of HCV mediated immune response with Fas triggered hepatocyte apoptosis giving rise to several amplification loops [36]. Similar findings were reported by others, who indicated in their study that the core protein could stimulate check details caspase-independent apoptosis at later stages of the disease giving relevance to the release of HCV particles from the host cells and to viral spread [46]. It has been shown that some HCCs are resistant to Fas-mediated apoptosis directly through

the expression of HCV proteins or indirectly through up-regulation of Bcl-2 family members [36]. Our data showed that both Bcl-2 and Bcl-xL RNA expression were significantly higher in HCC than in CH and NDT indicating late involvement of those genes in the cascade of HCV-associated hepatocarcinogenesis. We were also able to detect Bcl-2 gene expression in HepG2 cells starting from day 1 post-infection until the end of the experiment, whereas the expression of Bcl-xL was not visible until

day 28 when it started to be expressed and its expression was closely associated with the presence of HCV in tumor cells (Table 3) suggesting that Bcl-2 is tumor related whereas Bcl-xL is a viral related. In this context, Bcl-2 was linked to inhibition of apoptosis via interfering with either the recruitment Nutlin-3a clinical trial of procaspase 8 to Fas receptors [47] or by preventing the release of cytochrome

C [5]. It has also been shown that the HCV core protein inhibits apoptosis at the mitochondrial level through augmentation of Bcl-xL expression with consequent inhibition of caspase 3 activation [16]. The HCV core protein could induce apoptosis in the Fas death way although this is achieved through the activation of Bax and Bak, both are important mediators of p53 mitochondrial function [5, 36]. Our results showed an increase in Bak-RNA expression at an early stage of HCV infection of HepG2 cells, which is also observed in tissue samples obtained from both CH and HCC patients compared to NDT samples. Our results provided enough evidence that the Bak gene can induce apoptosis in HCC cells even in the presence of high levels of the anti-apoptotic Bcl-2 gene family members, which is in agreement with the findings Thiamet G of others [48]. The results of gene expression in tissue samples show a significant correlation between Fas expression in HCC cases and the presence of cirrhosis or poorly differentiated tumors. We observed that FasL expression was significantly associated in CH patients with the grade of inflammation and the stage of fibrosis as well as with the presence of severe necro-inflammatory changes. Based on these results we conclude that aberrant expression of Fas and FasL in HCV-infected patients could be considered a marker for increased disease severity with a higher possibility of progression into cirrhosis and/or HCC.

2005). Overall, the levels of inhalable dust seems to have declined by 4% per year since 1975 in compounding, mixing and pre-treatment departments which often are male-dominated in Sweden (de Vocht et al. 2007a, b), but no decline was observed in curing departments during the 1990s. For post-treating departments, where many women are employed, there were no data to allow modeling of exposure trends. A marked decrease in air levels of organic solvents was observed during the 1970s https://www.selleckchem.com/products/lazertinib-yh25448-gns-1480.html and early 1980s, with continuing decrease, thereafter (ExAs Rub 2004). Recently, extensive occupational hygiene measurements have been performed in the

Swedish rubber industry. The surveys were performed mainly in curing areas, and in areas with combined curing and post-processing procedures. High levels

of nitrosamines selleck kinase inhibitor in air were detected in certain curing processes (de Vocht et al. 2007a). Also, elevated urinary levels of phthalates (Vermeulen et al. 2005), and 1-hydroxypyrene as an indicator of PAH-exposure were detected at certain work tasks (Balogh et al. 2003). Measurements from other work areas dominated by female workers, as post-processing procedures, still are scarce. Also, there are few measurements from the male-dominated mixing areas. Although the substances for which modeling of exposure levels and time trends are available might not be the pertinent ones for reproductive outcome, overall changes

in exposure levels due to better workplace hygiene will indeed be reflected. In this perspective, it is intriguing find more that we observed a stronger effect on birth-weight, offspring sex ratio, and preterm births during the latter part of the observation period in our study, i.e. after 1987. We have at present no good explanation to this finding. Better exposure estimates, not only for chemical exposures but also for other factors that may affect reproductive outcomes, are indeed needed to elucidate this unexpected finding. From occupational settings outside the rubber industry, there are some indications that paternal solvent exposure is associated with an increased time to pregnancy (Sallmén et al. 1998), and inconsistent findings of low birth weight or preterm birth and spontaneous abortions (Lindbohm 1999). Experimentally, diethylnitrosamine has been shown to be hormonally active (Liao et al. 2001), as well as phthalates (Hoppin et al. 2002). There is evidence from animal data that phthalates have adverse reproductive effects in males (Foeter et al. 2001; Gray et al. 2000; Mylchreest et al. 2002; Nagao et al. 2000), and possibly also females (Ema and Miyawaki 2001). Also, some phthalates have been associated with adverse effects on semen quality in infertile or subfertile couples (Duty et al. 2003; Rozati et al. 2002).