BACKGROUND

The concentrations of the globulin binding of sexual hormones (GBSH) and serum and saliva testosterone were studied, as well as the free testosterone index (FTI), in a group of 75 premenopausic women of 42 years of age. These concentrations were correlated with the body mass index (BMI) and the relationship between the waist and hip perimeters (WHI) as an index of body fat distribution.

METHODS

Anthropometric measurements were performed in all the women studied. The BMI was used to classify the women as obese or not obese, while the WHI was used to classify fat distribution as android or gynoid type. The hormone determinations were carried out by radioimmunoassay and the GBSH by fluorescence immunoassay.

RESULTS

A significant positive correlation was observed between FTI and BMI (p = 0.024) and a negative correlation was seen between GBSH and WHI (p = 0.024). A significant decrease was found in the GBSH levels in obese women with respect to those who were not obese (p = 0.025) and between those with android fat distribution versus gynoid fat distribution (p = 0.032).

CONCLUSIONS

The modifications observed in the concentrations of the globulin binding sexual hormone in obese premenopausic women and the absence of the same in the free testosterone indexes may be explained because of other steroids such as androstenodiol and dehydrotestosterone are elevated. The measurement of globulin binding sexual hormone concentrations may be an early marker of alteration in the androgenic status in obese women.

OBJECTIVE

To describe patient characteristics according to different diagnostic criteria in early pregnancy, in women with polycystic ovary syndrome (PCOS).

METHODS

Descriptive, cross-sectional study of 257 women with PCOS in the first trimester of pregnancy.

METHODS

Data from a multicenter trial at the time of inclusion.

METHODS

257 PCOS women with singleton pregnancies.

METHODS

Investigator-administrated questionnaires were filled out. Clinical examination was performed by the investigators. Fasting blood samples were collected.

METHODS

Biometric data, androgens, glucose and insulin levels.

RESULTS

Women who met the National Institutes of Health (NIH) criteria for PCOS had higher body mass index (BMI), testosterone, dehydroepiandrostenedione, free testosterone index (FTI) and insulin levels compared with those who only met the Rotterdam consensus criteria. Adjusted for age and BMI, only testosterone and FTI were higher in those who met the NIH criteria. BMI was a strong, independent predictor of both systolic and diastolic blood pressure in early PCOS pregnancy, while both FTI and fasting insulin were independent predictors of systolic blood pressure. Twenty-two (9%) of the participants had gestational diabetes mellitus in the first trimester of pregnancy.

CONCLUSIONS

In the first trimester, PCOS women diagnosed according to NIH criteria were more metabolically and endocrinologically abnormal compared with those who only met the Rotterdam consensus criteria. BMI and FTI were independent predictive factors for blood pressure. There was a high prevalence of gestational diabetes mellitus in early PCOS pregnancies.

A rapid and simple method is described for the indirect measurement of free thyroxine (T4) concentration and maximal thyroxine-binding globulin (TBG) capacity applying a single kit of Thyopac-4. Initially, a value for total T4 is determined, after which the patient's serum is added to permit estimation of T4 corrected for abnormal TBG concentration. The ratio of increased radioactivity in the supernatant after the addition of patient's serum to that obtained using pooled normal serum is designated the TBG index, being directly related to the amount of TBG in the added serum. The index is significantly increased in hypothyroidism and pregnancy, and decreased in hyperthyroidism, correlating well with the TBG capacity measured by reverse-flow paper electrophoresis. A free T4 index (FTI) can be calculated from the values for T4 and TBG index, because the TBG index is reciprocally related to the serum uptake test (T3-resin). Values for FTI are significantly increased and decreased in hyper- and hypothyroidism, respectively, whereas they remain within the normal range in pregnancy and TBG deficiency. The FTI is shown to bear a nearly straight-line relationship to that calculated from separate estimations of T4 and the serum uptake test (T3-resin).

OBJECTIVE

To evaluate relationship between serum level of leptin and the components of risk factors for metabolic syndrome and to analyze the characteristics and laws of clustering of the risk factors.

METHODS

Totally, 795 non-diabetic adult Chinese subjects (691 men and 104 women, aged 40 - 75 years) from a diabetes prevalence survey in 2000 were involved in this study. Measurements included serum levels of true insulin (TI), leptin, fasting lipids, fasting glucose (FBG) and 2 h postchallenge glucose, as well as seated blood pressure (BP), body mass index (BMI), ratio of waist circumference to hip circumference (WHR), calculated quantitative insulin sensitivity check index (QUICKI), etc. Relationship between serum level of leptin and all the variables mentioned above was studied by statistical methods such as factor analysis, etc.

RESULTS

Serum level of leptin in the study subjects increased with the number of components of abnormal metabolism they had. Detection rates of obesity, hypertension, dyslipidemia and metabolic syndrome were significantly higher in those with the upper tertile of serum leptin level than in those with the lower tertile. Factor analysis revealed that variation of the 11 variables including serum level of leptin was affected by the three factors, i.e., the central factor associated with BMI, WHR, FTI, QUICKI and higher serum level of triglyceride (TG) and lower serum level of high-density lipoprotein-cholesterol (HDL-C), the glucose intolerance factor loaded with blood glucose level, FTI, QUICKI and higher serum level of TG (in women only) and the hypertension factor loaded with blood pressure and BMI (in men only), which could explain 62.0% and 66.7% of total variance in men and women, respectively, and higher serum level of TI and insulin resistance also loaded with both the central factor and glucose tolerance factor.

CONCLUSIONS

Serum level of leptin was significantly associated with the key markers of metabolic syndrome. Hyperleptinaemia could be a new component of metabolic syndrome. Clustering of the risk factors for metabolic syndrome could be affected by many factors, and although insulin resistance played an important role in it, insulin resistance alone could not explain its etiology.

The effects of yeast extract (0-10 g/l), methanol (0-10% v/v), acetic acid (0-1.0 g/l), furfural (0-0.5 g/l), glucose (0-30 g/l), inoculum age (15-70 h) and product concentration (18-230 g/l) on the xylose-xylitol conversion by Candida guilliermondii FTI 20037 were studied. The xylitol specific productivity increased about 35% at a yeast extract concentration of 1.0 g/l, whereas glucose showed a strong inhibitory effect on the xylitol production and a stimulating effect on the growth of C. guilliermondii. Methanol, acetic acid and furfural under the employed concentrations did not show any positive effect neither on the growth or on the xylose-xylitol conversion by the yeast. The inoculum age showed a strong influence on xylitol formation and the best fermentative parameters were attained using a 40-h inoculum age. A xylitol concentration in the fermentation medium higher than 80 g/l inhibited markedly the xylitol productivity by the yeast C. guilliermondii.

We studied 145 clinically euthyroid patients on maintenance methadone therapy for narcotic withdrawal, to characterize abnormalities in thyroid-function tests induced by methadone. About a third had increased total thyroxin (T4) and total triiodothyronine (T3) concentrations in serum. The mean concentrations of T3, T4, and thyroxin-binding globulin (TBG) in serum were significantly greater (P less than 0.001 each) in these patients than in a euthyroid control group. There was a corresponding decrease in the T3 uptake (T3U) test, but the free thyroxin index (FTI) failed to correct for the increased TBG concentration in 15.9% of the patients. Individual and mean concentrations of free T3 (FT3) and free T4 (FT4) in serum and results of an "ultrasensitive" test for thyrotropin (TSH-IRMA) were within normal limits and confirmed the euthyroid state. We conclude that prolonged therapy with methadone causes increases in TBG, T3, and T4 in serum. FT3, FT4, and TSH-IRMA estimations are recommended as the diagnostic thyroid tests to use for patients on methadone maintenance therapy.

The thyroid functional parameters of 102 children with protein-calorie malnutrition (PCM) classified as undernourished, marasmic, kwashiorkor and marasmic-kwashiorkor were studied by measuring the serum T4, T3, T3 percentage uptake (T3%UT), free thyroxine index (FTI), and (in a few subjects) TSH. Total plasma proteins, albumin and globulin were also estimated. T4 was increased markedly in the undernourished children and significantly decreased in kwashiorkor and marasmic-kwashiorkor groups. There was a consistent and significant fall in T3 levels of all PCM children. From normal values, the fall in T3 levels was progressive in the order of undernourished, marasmic, kwashiorkor and the marasmic-kwashiorkor states. The T3%UT was increased above normal in the marasmic, kwashiorkor and marasmic-kwashiorkor conditions. The FTI decreased somewhat in marasmus and kwashiorkor groups and was very low in marasmic-kwashiorkor. Total protein and albumin levels were above normal in the undernourished but became markedly depressed in the marasmic-kwashiorkor children. The changes in the levels of both T4 and T3 in our observations are well correlated with the levels of plasma proteins in the undernourished, marasmic and kwashiorkor states but not in the marasmic-kwashiorkor group.

The evaluation of hexose and pentose in pre-cultivation of Candida guilliermondii FTI 20037 yeast on xylose reductase (XR) and xylitol dehydrogenase (XDH) enzymes activities was performed during fermentation in sugarcane bagasse hemicellulosic hydrolysate. The xylitol production was evaluated by using cells previously growth in 30.0 gl(-1) xylose, 30.0 gl(-1) glucose and in both sugars mixture (30.0 gl(-1) xylose and 2.0 gl(-1) glucose). The vacuum evaporated hydrolysate (80 gl(-1)) was detoxificated by ion exchange resin (A-860S; A500PS and C-150-Purolite®). The total phenolic compounds and acetic acid were 93.0 and 64.9%, respectively, removed by the resin hydrolysate treatment. All experiments were carried out in Erlenmeyer flasks at 200 rpm, 30°C. The maximum XR (0.618 Umg (Prot) (-1)) and XDH (0.783 Umg (Prot) (-1)) enzymes activities was obtained using inoculum previously growth in both sugars mixture. The highest cell concentration (10.6 gl(-1)) was obtained with inoculum pre-cultivated in the glucose. However, the xylitol yield and xylitol volumetric productivity were favored using the xylose as carbon source. In this case, it was observed maximum xylose (81%) and acetic acid (100%) consumption. It is very important to point out that maximum enzymatic activities were obtained when the mixture of sugars was used as carbon source of inoculum, while the highest fermentative parameters were obtained when xylose was used.

Sugarcane bagasse, an agricultural residue plentiful in Brazil, was utilized for xylitol production by a biotechnological process. A medium fermentation prepared with this xylose-rich biomass at an oxygen transfer volumetric coefficient of 10/h1 and different initial pH values was inoculated with cells of Candida guilliermondii FTI 20037. The maximum values of xylitol and cell volumetric productivities (Qp = 0.56 g/[L.h] and Qx = 0.11 g/[g.h]), xylitol yield factor (YP/S = 0.79 g/g), and xylose uptake rate (qs = 0.197 g/[g.h]) were attained at pH 7.0 without further pH control. The results show that the yeast performance was influenced by the pH, an important bioengineering parameter in this fermentation process.

Previously, we reported the potential of a novel Cdk inhibitor, 2-[1,1'-biphenyl]-4-yl-N-[5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-1H-indazol-3-yl]acetamide (BAI) as a cancer chemotherapeutic agent. In this study, we investigated mechanisms by which BAI modulates FTI-mediated apoptosis in human renal carcinoma Caki cells. BAI synergizes with FTI to activate DEVDase, cleavage of poly ADP-ribose polymerase (PARP), and degradation of various anti-apoptotic proteins in Caki cells. BAI plus LB42708-induced apoptosis was inhibited by pretreatment with pan-caspase inhibitor, z-VAD-fmk, but not by overexpression of CrmA. The ROS scavenger, N-acetylcysteine (NAC) did not reduce BAI plus LB4270-induced apoptosis. Co-treatment of BAI and LB42708 reduced the mitochondrial membrane potential (MMP, ∆Ψm) in a time-dependent manner, and induced release of AIF and cytochrome c from mitochondria in Caki cells. Furthermore, BAL plus LB42708 induced downregulation of anti-apoptotic proteins [c-FLIP (L), c-FLIP (s), Bcl-2, XIAP, and Mcl-1 (L)]. Especially, we found that BAI plus LB42708-induced apoptosis was significantly attenuated by overexpression of Bcl-2 and partially blocked by overexpression of c-FLIP (L). Taken together, our results show that the activity of BAI plus LB42708 modulate multiple components in apoptotic response of human renal Caki cells, and indicate a potential as combinational therapeutic agents for preventing cancer such as renal carcinoma.

The use of chlorotrityl resins for the immobilization of amines is sometimes deterred by the lengthy process of loading the reactants on the resins and product decomposition caused by the reactive chlorotrityl group in the presence of 1% TFA as a cleavage agent. Here, we report improved methods developed for selective and efficient loading of aminobenzoic acid derivatives on chlorotrityl resins and for cleavage of aniline-containing products from the resins without decomposition. These methods led to the synthesis of a library of 144 discrete chemicals as potential farnesyltransferase inhibitors (FTIs) using IRORI's radio-frequency-encoded sorting technique and to the study of the applicability of the bivalence approach to the development of FTIs.

OBJECTIVE

The pathogenesis of hyperemesis gravidarum (HG) is probably multifactorial, involving several hormones. Androgen concentrations are reported to correlate positively with emesis gravidarum. Hypothesizing a continuum between emesis gravidarum and HG, we investigated androgen concentrations in women with HG.

METHODS

In a case-control study, 32 women hospitalized for HG were compared with 29 control women scheduled for elective surgical abortion. Control women were matched for age, gestational length, body mass index (BMI) and parity. Patient characteristics and concentrations of dehydroepiandrosterone sulphate (DHEAS), androstenedione, testosterone, sex hormone binding globulin (SHBG), free testosterone index (FTI), androstanediol glucuronide (ADG), progesterone, TSH, free T3 and T4, beta-hCG, ferritin, insulin, estradiol and estriol were compared using Mann-Whitney tests and multivariate linear regression analyses.

RESULTS

Women with HG had higher concentrations of ADG (8.49±4.19 vs. 6.19±1.77pmol/L; p=0.015), estradiol (2.39±1.36 vs. 1.60±9.30nmol/L; p=0.009) and ferritin (186±138 vs. 117±94pmol/L; p=0.040) compared with control women. Androstenedione (5.34±2.82 vs. 6.86±2.67; p=0.004) and insulin (63.7±35.0 vs. 75.3±25.8; p=0.050) concentrations were lower in women with HG. DHEAS, testosterone, FTI, SHBG, estriol, progesterone, beta-hCG, TSH, free T3 and free T4 concentrations did not differ between the groups. In multivariate regression analyses HG was associated with high concentrations of ADG (p=0.026) and low concentrations of androstenedione (p=0.018).

CONCLUSIONS

Steroid hormone homeostasis may be altered in women with HG. HG may be associated with high ADG and low androstenedione concentrations.

It is known that the potential clinical use of farnesyltransferase inhibitors (FTI) could be expanded to include cancers harboring activated receptor tyrosine kinases. Approximately 70% of malignant pleural mesotheliomas (MPM) overexpress epidermal growth factor receptors (EGFR) and a subset express both EGFR and transforming growth factor alpha (TGF-alpha), suggesting an autocrine role for EGFR in MPM. We checked on MPM cells (10 human cell lines, 11 primary cultures obtained by human biopsies, and 7 short-term normal mesothelial cell cultures) concerning the following: (a) the relative overexpression of EGFR (Western blotting, flow cytometry, immunohistochemistry), (b) the relative expression of EGFR ligands (EGF, amphiregulin, TGF-alpha, ELISA), (c) the relative increase of the activated form of Ras (Ras-bound GTP) after EGF stimulation (Ras activation assay), (d) the efficacy of five different FTIs (HDJ2 prenylation, cell cytotoxicity, and apoptosis using ApopTag and gel ladder). EGFR was overexpressed in MPM cells compared with normal pleural mesothelial cells in equivalent levels as in non-small cell lung cancer cells A459. MPM cells constitutively expressed EGFR ligands; however, Ras activation was attenuated at high EGF concentrations (100 ng/mL). Growth of MPM cells was substantially not affected by treatment with different FTIs (SCH66336, BMS-214662, R115777, RPR-115135, and Manumycin). Among these, BMS-214662 was the only one moderately active. BMS-214662 triggered apoptosis in a small fraction of cells (not higher than 30%) that was paralleled by a slight decrease in the levels of TGF-alpha secreted by treated MPM cells. Our data highlighted the concept that the same signaling pathway can be regulated in different ways and these regulations can differ between different cells of different origin.

The relationships among lumbar and femoral bone mineral density (BMD) and different forms of testosterone--total, salivary testosterone and free testosterone index (FTI) calculated with the sex hormone binding globulin (SHBG)--, body mass index (BMI) and body fat distribution (waist-to-hip ratio and breast-to-hip ratio) were analysed in a cross-sectional study with 66 Spanish premenopausal healthy women aged 42 years and with normal levels of serum testosterone. BMD was measured using dual-energy X-ray absorptiometry (Hologic QDR 1000), and salivary and blood samples were obtained during early follicular phase. In a multiple stepwise regression analysis, lumbar BMD was positively predicted by salivary testosterone and negatively by SHBG adjusted by BMI (R2 = 0.20; p < 0.02). The most femoral BMDs were negatively predicted by SHBG and positively by breast-to-hip ratio (R2 = 0.22-0.33, according to the site measured), but neck BMD was not predicted by any variable. When FTI was entered into the regression model instead of SHBG, it was not an independent predictor of BMD. The waist-to-hip ratio was positively correlated with several femoral BMD sites, but breast-to-hip ratio was better predictor. After adjusting by SHBG, the BMI was only predictor for intertrochanter BMD. All women with elevated salivary testosterone (n = 12) had higher lumbar BMD than those with normal value (1.120 +/- 0.112 vs. 1.026 +/- 0.118; p < 0.01) without differences in other confounding variables. As a conclusion, in premenopausal healthy women of the same age with normal levels of serum testosterone, low levels of SHBG and high levels of salivary testosterone are associated with higher lumbar BMD, whereas low levels of SHBG together with higher breast-to-hip ratio are associated with higher femoral BMD.

A trial was carried out on 134 patients of new kits (Ames Co) using columns of Sephadex G-25 for the determination of serum total thyroxine (Tetralute test) and for the indirect estimation of serum free thyroxine-binding globulin capacity (Trilute test). Both new methods were quicker and easier than the reference resin methods and of similar precision. The two measurements when combined to give a free thyroxine index (Trilute-Tetralute-FTI) increased further the diagnostic discrimination and usefulness of the tests. The method for the determination of serum thyroxine can be modified to give a direct estimate of serum free thyroxine, expressed as a free thyroxine index. This new single-column technique, called the ;single-column free thyroxine index', gave a good correlation with clinical thyroid status in a preliminary trial of 45 patients.

Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulation of long-lived neoplastic plasma cells (PC) within the bone marrow (BM). Novel treatments are not only targeting myeloma cells but also directly interfere with myeloma-stromal cell interactions, interrupting signal transduction pathways. Farnesyltransferase inhibitors (FTIs) and rapamycin represent novel classes of signal transduction inhibitors targeting principally Ras/MAPK and PI3K/Akt pathway. Pre-clinical and early clinical reports are presented in this study.

OBJECTIVE

To determine the effect of 2 cold-water-immersion (CWI) temperatures (15°C and 8°C) on repeat handgrip performance to failure.

METHODS

A total of 32 participants completed 3 intermittent trials to failure on a climbing-specific handgrip dynamometer on 3 laboratory visits. For each visit, a different recovery strategy was employed: passive (PAS) recovery, CWI at 8°C (CW8), or CWI at 15°C (CW15). The force time integral (FTI: time of contraction multiplied by the force of contraction) was determined to assess handgrip performance.

RESULTS

There was no significant difference between recovery strategies at the end of trial 1. In response to the PAS recovery strategy, there were 10% and 22% decreases in FTI in the second and third trials, respectively. The PAS recovery-strategy FTI values were lower than both CWI strategies for trials 2 and 3 (P < .05). FTI increased in the second trial (↑32% and ↑38%; P < .05) for both immersion strategies (CW8 and CW15, respectively) compared with trial 1. During the third trial, FTI was significantly higher for CW15 than CW8 (↑27% and ↓4% with respect to baseline trial; P < .05).

CONCLUSIONS

The results suggest that CWI has potential performance advantages over PAS recovery for rock climbing. The data show that in events where multiple recoveries are required, 15°C CWI may be more beneficial for climbers than 8°C CWI. Future research should focus on the optimization of protocols for sport performance.

As one of the world's five terminally ills, tumours can cause important genetic dysfunction. However, some current medicines for tumours usually have strong toxic side effects and are prone to drug resistance. Studies have found that farnesyltransferase inhibitors (FTIs) extracted from natural materials have a good inhibiting ability on tumours with fewer side effects. This article describes several FTIs extracted from natural materials and clarifies the current research progress, which provides a new choice for the treatment of tumours.

Danazol is a synthetic steroid with antigonadotropic properties useful in treating endometriosis, especially in young infertile women. Prior to its availability for clinical use in September 1976, thyroid function studies other than thyroid-stimulating hormone (TSH), which was normal, had not been reported. Soon after danazol began to be used in the infertility clinic to treat documented endometriosis, it was observed that changes occurred in thyroid function studies. While no patients manifested clinical evidence of hypothyroidism, all 8 patients receiving 800 mg of danazol daily for 1 to 5 months had laboratory evidence of decreased thyroid function. The triiodothyronine (T3) uptake was elevated and the total serum thyroxine (T4) was decreased. The finding that TSH and the free thyroid index (FTI) were normal confirmed that these patients were euthyroid during danazol therapy. The abnormality of thyroid function tests is believed to reflect an androgen-like reduction in thyroxine-binding protein rather than a true decrease in thyroid function or interference with the pituitary-thyroid axis.

Patients with acute myelogenous leukemia or myelodysplastic syndrome may respond to farnesyl transferase inhibitors (FTIs) with partial or complete response rates noted in about 30% of such patients. FTIs prevent the attachment of a lipid farnesyl moiety to dependent proteins prior to their insertion into the plasma membrane and thereby prevent activity of these prenylation-dependent proteins, but their mechanism of tumor suppression remains unknown. Many patients receiving FTIs do experience myelosuppression. In this work, the in vitro effects of the FTI, R115777 on normal and leukemic hematopoiesis have been examined as have its effects on apoptosis induction and cell cycle profile in both leukemic blasts and normal CD34+ cells. R115777 was inhibitory to normal CD34+ cell proliferation and to leukemic blast cells, but did not affect long-term culture initiating cell frequency nor NOD-SCID reconstituting capacity. No induction of apoptosis or cell cycle changes were noted in AML blasts. These data suggest that myelosuppression with R115777 occurs largely at the intermediate to late progenitor stage of hematopoiesis and that cyclic use might avoid long-term marrow suppression.

Farnesyltransferase inhibitors (FTIs) represent a novel class of anticancer drugs and are now in clinical trial. We have previously shown that farnesylamine, synthetic isoprenoid-linked with "amine" which acts as a potent FTI, induces apoptosis in human pancreatic cancer cells through the ras signaling cascade. Since the effect of FTI is usually "cytostatic" rather than "cytotoxic", we speculated another apoptotic machinery of farnesylamine in addition to the effect of FTI. Farnesylamine induced sustained activation of c-jun N-terminal kinase (JNK), which was not caused by other FTI, FTI-277. Blockage of JNK activity by dominant-negative mutant abrogated the DNA laddering and significantly reduced "cytotoxic" effect of farnesylamine. Strikingly similar effect on JNK activation and apoptosis was induced by structurally related long-chain fatty amine (LFA), oleylamine, but not by farnesol, an isoprenoid analogue of farnesylamine without "amine." Taken together, apoptosis induction through JNK activation by farnesylamine based on the LFA structure rather than an effect of FTI.

BACKGROUND

Fluid overload is an important and modifiable cardiovascular risk factor for haemodialysis patients. So far, the diagnosis was based on clinical methods alone. Nowadays, we have new tools to assess more objectively the hydration status of the patients on haemodialysis, as BCM (Body Composition Monitor). A Relative Overhydration (AvROH) higher than 15% (it means, Absolute Overhydration or AWOH higher than 2.5 Litres) is associated to greater risk in haemodialysis. However, there is a group of maintained hyperhydrated patients. The aim of the present study is to identify the characteristics of patients with maintained hyperhydrated status (AvROH higher than 15% or AWOH higher than 2.5 liters). The secondary aim is to show the hemodynamic and analytical changes that are related to the reduction in hyperhydration status.

METHODS

Longitudinal cohort study during six months in 2959 patients in haemodialysis (HD) that are grouped according to their hydration status by BCM. And we compare their clinical, analytical and bioimpedance spectroscopy parameters.

RESULTS

The change in overhydration status is followed by a decrease in blood pressure and the need for hypotensive drugs (AHT) and erythropoiesis stimulating agents (ESA). The target hydration status is not reached by two subgroups of patients. First, in diabetic patients with a high comorbidity index and high number of hypotensive drugs (AHT) but a great positive sodium gradient during dialysis sessions; and, younger non-diabetic patients with longer time on hemodialysis and positive sodium gradient, lower fat tissue index (FTI) but similar lean tissue index (LTI) and albumin than those with a reduction in hyperhydration status.

CONCLUSIONS

Those patients with a reduction in hyperhydration status, also show a better control in blood pressure and anemia with less number of AHT and ESA. The maintained hyperhydrated patients, diabetic patients with many comorbidities and young men patients with longer time on hemodialysis and non-adherence treatment, can profit from a constant monitoring of their hydration state as well as an individualized treatment (dialysis and drugs).

Purpose: Paclitaxel is a generic drug produced based on Taxol which is an extract of Taxus tree, well known for its anticancer and antibacterial effects. This study was aimed at building up an agent with the antibacterial and anticancer benefits of both the silver ions and Taxol, together with less cytotoxic effects.

Materials and methods: Colloidal silver nanoparticles (AgNPs) were synthesized by reducing aqueous AgNO₃ with aqueous Taxus leaf extract at nonphotomediated conditions, without any catalyst, template or surfactant. The AgNP production was confirmed by ultraviolet-visible (UV-VIS) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier-transform infrared (FTI) spectroscopy. The MTT assay for human breast cancer cells as well as the DAPI fluorescent staining microscopy tested the biocompatibility and anticancer effects of AgNPs, silver nitrate, and Taxol. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques were performed to determine the shape and size of the nanoparticles. MTT assay showed the best inhibitory concentration of AgNPs on cancer cells. The antibacterial activity of the three case study materials was tested for gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using well diffusion test.

Results: This work proposes more anticancer effects for AgNP made by Taxus brevifolia extract, comparing Taxol solution. IC50 was observed as 3.1 mM for Taxol while 1.5 mM for new AgNP. Moreover, Taxus showed no antibacterial effects while the new AgNP showed a dose-dependent biocompatibility along with slightly more antibacterial effects (MIC: 1.6 and 6.6mM for gram-positive and -negative bacteria, respectively) comparing with silver nitrate solution (MIC: 1.5 and 6.2 mM for gram-positive and -negative bacteria, respectively).

Conclusion: The production of herbal-mediated silver nanoparticles may be an efficient substitution for the silver nitrate-based medicines with less side effects.

Keywords: Taxus tree extract; antibacterial; anticancer; green synthesis; silver nanoparticle.