Low Dose

There are two families of dopamine (DA) receptors, called D1 and D2, respectively. The D1 family consists of D1- and D5-receptor subtypes and the D2 family consists of D2-, D3-, and D4-receptor subtypes. The amino acid sequences of these receptors show that they all belong to a large superfamily of receptors with seven transmembrane domains, which are coupled to their

Background: is involved in the apical migration of epithelial cells during the development of periodontal pockets. Low-dose doxycycline (LDD) can therapeutically modulate the host response with its non-antimicrobial properties. In the present randomized, double-blind, placebo-controlled, parallel arm study, the effectiveness of LDD in combination with non-surgical periodontal therapy on gingival crevicular fluid (GCF) Ln-5 γ2 chain fragment levels and clinical parameters in patients with chronic periodontitis was examined over a 12-month period.

Objecti®e: The purpose of this study was to evaluate the efficacy and safety of intravaginal misoprostol for labor induction. Methods: 110 singleton term pregnancies with or without rupture of membranes were enrolled. Fraction-Ž. ated doses of misoprostol were applied 50᎐100 g , every 6 h until a maximum of three doses or beginning of labor. Ž. Results: The average interval "S.D. from vaginal application to the beginning of active labor and to delivery were, Ž. respectively, 9.5" 5.7 h and 14.8" 9.5 h. Failed labor induction was observed in two cases 2%. Cesarean section rate was 14%. The incidence of tachysystole was 18% and hypersystole 4%, but these situations were associated with Ž. abnormal fetal heart rate pattern hyperstimulation in only 3%. No maternal side effects and neonatal adverse effects were noted. Conclusions: Intravaginal misoprostol administration with low doses is an effective and safe method for labor induction in term pregnancies, with or without rupture of membranes.

. Miral 500 CS CASa 42509-80-8 , an organophosphorus insecticide, has been widely used in Colombia to fumigate coffee plantations. Therefore, there is extensive human exposure to this pesticide. Miral's mutagenic and genotoxic activities, however, are not known. In this study, such activities of the pesticide were evaluated using the Salmonella TA98rS9 test and the chromosome aberration assay in bone marrow cells of Swiss albino CD1 male mice. All doses tested Ž . with Salmonella in the presence of S9 mix 3.2, 16, 80, 400 and 2000 mgrplate induced a mutagenic response that was three times the spontaneous mutation frequency. The mutagenic response without S9 was twice the spontaneous frequency.

Background: Low-dose naltrexone (LDN) may promote psychological well-being as well as generalized health especially in autoimmune disorders. The objective of this study is to assess the effect of LDN on the Quality of Life (QoL) of patients with relapsing—remitting and secondary progressive multiple sclerosis (MS) using the scales and composite scores of the MSQoL-54 questionnaire. Methods: A 17-week randomized, double-blind, placebo-controlled, parallel-group, crossover-design clinical trial was conducted in two universities. A total of 96 adult patients aged between 15 and 65 years with relapsing—remitting (RR) or secondary progressive (SP) clinically definite MS with disease duration longer than 6 months enrolled into the study. The primary outcome of the study was comparison of the scores of physical and mental health by conducting independent t-test of the results obtained in the middle and at the end of study between the two groups. Results: Variables including presence of pai...

RESUMEN Introduccion: bexaroteno es un rexinoide aprobado en el tratamiento de estadios tempranos y avanzados del linfoma cutaneo de celulas T (LCCT). Caso Clinico: el presente reporte de casos mostramos los resultados del empleo de bexaroteno en dosis bajas mas fototerapia o Interferon alfa 9 millones en el tratamiento del LCCT. Ocho pacientes fueron tratados , cinco fueron Micosis fungoides, dos Linfoma Epidermotropico CD8 agresivo y uno fue un Sindrome Sezary. La respuesta global fue del 62.5% (5/8) y la duracion media de respuesta fue de 20 meses. El bexaroteno en dosis bajas en combinacion a fototerapia o interferon alfa 2a puede ser efectivo en el tratamiento del LCCT. Palabras clave: linfoma cutaneo de celulas T, bexaroteno, interferon alfa.

Non-linear phenomena in biological findings of the residents of high background radiation areas of Ramsar background dose rates among the highest known in the world. As the biological effects of low doses of radiation are not fully understood (2, 3) , the current radiation protection recommendations are based on the predictions of an assumption on the linear non-threshold hypothesis (LNT) relationship between radiation dose and its carcinogenic effects (4, 5). Considering the LNT hypothesis as a scienti ic fact, there is a general belief that even low levels of radiation as well as exposures to natural

Inducible expression of tetracycline responsive element (TRE)-regulated genes in nearly all cells in a stable clone has generally been problematic, especially in long-term culture. Heterogeneity of tet-inducible expression is generally attributed to the instability of the original tet-transactivators tTA and rtTA. These transactivators have cryptic splice sites, prokaryotic codons and full VP16 domains, all of which contribute to their instability. Moreover, they also require high concentrations of Doxycycline (Dox). The 5 amino acid substitutions in the rtTA variant rtTA2S-M2 confer exquisite sensitivity to Dox. Moreover, humanized codons, removal of cryptic splice sites and minimal VP16 domains in rtTA2S-M2 results in its being better tolerated within cells. However, the ability of this modified transactivator to maintain homogeneous inducibility in long-term culture has not been examined. We demonstrate that rtTA2S-M2 expressing clones exhibit functional transactivator activity for over 7 months in culture. Furthermore, rtTA2S-M2 expressing clones with chromosomally integrated copies of a TRE -green fluorescent protein (GFP) reporter also exhibited homogeneous inducibility in long-term culture. Importantly, the inherent reduced toxicity and improved stability of rtTA2S-M2 obviates the need to continuously select for its message, once clones with functional transactivator are isolated. The use of rtTA2S-M2 did not, however, preclude clones with stably integrated TRE-reporter from exhibiting leakiness. However, inclusion of flanking double copies of a 'minimal core element' of the chicken h-globin gene insulator, instead of the 1.4 kb region, in the TRE-reporter was sufficient to markedly reduce the frequency of clones with high basal expression. Inclusion of the insulator core also did not affect the maximal expression levels of the inducible gene, which typically equaled or exceeded that observed with the strong constitutive CMV promoter. Finally, with this system homogeneous inducibility was observed rapidly and with low doses of Dox. D

Dynamic Energy Budget (DEB) theory provides a powerful framework for interpreting toxicity data, but is not broadly applied in ecotoxicology yet. One of the reasons is the fact that estimation of DEB parameters from experimental data is certainly not a trivial affair. Almost every data analysis raises new questions, which require the formulation of specific mechanistic hypotheses. These hypotheses should be translated into model adaptations, which can subsequently be tested on the data set. In this paper, we demonstrate this procedure by analyzing a case study for ecotoxicity within the DEB framework. The case study we selected is a previously published data set for 4-n-nonylphenol in the polychaete worm Capitella teleta (formerly Capitella sp. I). Particular aspects of interest in this study are an apparent slow initial growth, and low-dose stimulation (hormesis) of growth and reproduction. In this publication, we explicitly discuss our deviations from the standard DEB model in terms of the underlying hypotheses, the existence of alternative hypotheses to explain the data, and how limited additional experiments can be designed to decide between alternative explanations.

Changes in contractility of newborn and adult hearts with different substrates were studied under oxygenation and hypoxia. Under oxygenation, insulin (50 mU/l) and low doses of fatty acids (sodium palmitate 0.12 mM) increased the differential ventricular pressure (DVP), while higher doses of fatty acids (from 0.3 to 1.5 mM) decreased it. However, when both low doses of fatty acids and insulin were added simultaneously, tension development decreased. Hypoxia reduced DVP, and low doses of fatty acids restored cardiac force. The contractile response to extracellular glucose concentrations changed during development, and sensitivity to high doses of fatty acids increased with age. In adult cardiomyocytes, glucose uptake was also inhibited by sodium palmitate under oxygenation when cardiac metabolism is fatty acid dependent, but not under hypoxia, when it consumes carbohydrates. Newborn cardiomyocytes consumed more glucose than adult cells, they did not respond to insulin, and palmitate did not completely inhibit glucose uptake neither under oxygenation nor under hypoxia. Substrate availability modified glucose uptake and contractility by independent mechanisms.

The effects of normal and controlled atmosphere combinations on tuber components responsible for acrylamide formation were studied during prolonged storage at 9±1 °C using the tubers of “Agria” and “Russet Burbank.” The effects of low-dose irradiation (50, 200 Gy) prior to normal atmosphere storage were also studied. There was only a limited increase in the concentrations of sugars during 6 month of storage under normal atmosphere conditions. Low-dose irradiation slightly decreased the rate of sweetening in the tubers. The potential of acrylamide formation remained almost the same; however, the loss of firmness became clearer during 6 month of storage under normal atmosphere conditions. Controlled atmosphere storage in which O2 was deficient to a sufficient respiration increased the concentrations of sugars, and thus, the potential of acrylamide formation in potatoes upon frying at 170 °C for 10 min. The sum of glucose and fructose concentrations showed a good correlation (r 2∼0.90) with the potential of acrylamide formation for both cultivars.

Background and purpose: Some types of radiation therapy have been associated with an increased risk of cardiac mortality and morbidity in patients with early-stage breast cancer. A relationship has been observed between cardiac radiation dose-volume and the level of excess risk of cardiac mortality. However, relatively few data are available on the morbidity from myocardial infarction associated with adjuvant radiotherapy.

The radiation response behaviour of high phosphorous doped step index multimode (SIMM) fibers of different P 2 O 5 concentrations and core diameters has been investigated in comparison with Ge doped SIMM fiber at different transmission wavelengths under 60 Co gamma irradiation with variation of dose rates from 1Rad/hr to 100Rad/hr. Radiation induced absorption curves of P doped fibres show two broad absorption peaks in the wavelength ranges 400-420nm & 500-560nm which arise due to phosphorous oxygen hole center defect. It has been observed that at 540nm & 560nm transmission wavelengths sensitivity shows strong dose rate dependence compared to that at 502nm wavelength but does not show any saturation behaviour. This reveals that P related defects do not anneal at room temperature and yield permanent change. The radiation sensitivity decreases with increasing transmission wavelengths from 502nm to 560nm with very low fading behaviour. The fiber containing 16mol% P 2O 5 with coreclad dimension of 42:125 micron has an excellent linear radiation response behaviour with sensitivity a round 1.0dB/m/100Rad at 502nm wavelength as well as very low recovery and dose rate independence. This enables its practical application in fiber optics personal dosimeter for measurement of low dose gamma radiation.

Background: Methotrexate has been implicated in a variety of lung complications, one of which is hypersensitivity pneumonitis. Hypersensitivity pneumonitis most often occurs within the first year of starting low-dose orally administered methotrexate. We present a case of methotrexate-induced hypersensitivity pneumonitis after 30 years of methotrexate use, which is the first case to be reported so far. Case presentation: A 77-year-old African American woman with a history of rheumatoid arthritis presented with progressively worsening shortness of breath and nonproductive cough. She was on a daily dose of 2.5 mg of methotrexate that had been orally administered for the last 30 years. A physical examination was significant for fever of 38.2°C (100.8°F), tachycardia, bilateral basal crackles, and oxygen saturation of 88% on room air. A laboratory work up was significant for normal white blood cell count, increased eosinophil count of 18.3%, and erythrocyte sedimentation rate of 111 mm/hour. Sputum cultures were negative for any bacterial pathogens including acid-fast bacilli. Influenza and respiratory syncytial viral infection were ruled out. A (1-3)-B-D-glucan assay (Fungitell®) was within normal limits. Pulmonary embolism was ruled out and echocardiography was normal. A chest X-ray showed hazy opacity with prominent reticulation within the upper lung fields bilaterally, right greater than the left with no pleural effusion. Lung computed tomography revealed nonspecific bilateral upper lung opacification. A pulmonary function test was significant for no obstruction, normal maximum voluntary ventilation, and no restriction, with mildly decreased diffusion. Methotrexate was stopped, and our patient was started on prednisone 60 mg orally administered daily with dramatic clinical and radiologic improvement. Conclusions: Methotrexate-induced hypersensitivity pneumonitis usually occurs in the initial few weeks to months of starting treatment with methotrexate; however, it can occur late during therapy too, and prompt diagnosis is crucial as it is a reversible condition when diagnosed early.

The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments.

Objective: To demonstrate the effects of 2-year transdermal continuous combined low-dose estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) on lipid/lipoprotein profile and coagulation/fibrinolysis. Methods: A double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years post menopause. Patients received either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo transdermally. One hundred and thirty five women completed a second year open follow-up (96 had used Estragest TTS, 39 placebo during the first year), where all women had the estradiol/norethisterone patch. Lipid/lipoprotein profile and coagulation/fibrinolysis parameters were studied at 0, 24, 48, 72 and 96 weeks. Results: In women on estradiol/norethisterone total cholesterol, Lp(a) and VLDL cholesterol decreased significantly more than in the placebo group after 24 weeks and LDL cholesterol after 48 weeks. Women on estradiol/norethisterone had no change in HDL, triglycerides or Lp(a), an increased HDL/total cholestrol ratio and decreased LDL, VLDL and total cholesterol at 48 weeks compared to placebo. Women with active treatment also showed a significant reduction compared with the placebo group of Factor VII and antithrombin III at 24 and 48 weeks and a reduction of fibrinogen at 24 weeks. These changes persisted over the second year. Conclusions: A continuous combined low-dose transdermal patch daily delivering 0.025 mg estradiol and 0.125 mg norethisterone acetate provided beneficial effects on lipid/lipoprotein profile and coagulation/fibrinolysis. The changes were similar to those previously described after higher dose oral and transdermal estrogen/progestogen regimens.

Mammalian cytotoxic T cells as part of the adaptive immune system recognize virus-infected target cells by binding of their T-cell receptors (TCR) to classical MHC class I molecules loaded with viral peptides. Our previous studies have shown that the allele of the single dominant polymorphic classical MHC class I locus Onmy-UBA is identical in the rainbow trout clone C25 and in the permanent rainbow trout cell line RTG-2. This enabled us to develop an assay to measure antiviral cytotoxicity in rainbow trout using a system of MHC class I-matched effector and target cells. Peripheral blood leucocytes (PBL) isolated from low dose viral haemorrhagic septicaemia virus (VHSV)-infected rainbow trout killed MHC class I-matched and later also xenogeneic MHC class I-mismatched VHSV-infected cells. When compared to PBL from uninfected control fish PBL from infected fish showed a higher transcriptional level of the CD8a gene which is a typical marker for mammalian cytotoxic T cells. Concurrently, the expression of the natural killer cell enhancement factor (NKEF)-like gene was enhanced as measured by real-time RTePCR. Taken together, these results suggest that both innate and adaptive cell-mediated immune responses represented by NK and cytotoxic T cells, respectively, are triggered after VHSV infection. PBL that were able to kill VHSV-infected MHC class I-mismatched xenogeneic cells were generated later during infection than PBL capable of lysing VHSV-infected MHC class I-matched targets. This is contradictory to the generally accepted rule that innate immune mechanisms represent the first line of defence after viral infections.

Central venous catheters are being increasingly used in both intensive care units and general wards. Their use is associated with both mechanical and infectious complications. This review will focus on short-and medium-term mechanical complications of catheter placement; infectious complications will be discussed in a separate article. The most important risk factors are patient characteristics (morbidity, underlying disease and local anatomy), the expertise of the doctor performing the procedure, and nursing care. Placement aids, such as ultrasoundguided catheter insertion, are also discussed.

Rotenone, a mitochondrial complex 1 inhibitor, causes oxidative damage via production of reactive oxygen species. We examined the pathophysiology of neuronal and glial cells of the nigrostriatal pathway following unilateral infusion of varying doses of rotenone into the substantia nigra or medial forebrain bundle of adult male Sprague-Dawley rats, sacrificed 14 and 60 days after infusion. Immunofluorescence techniques were used to qualitatively and quantitatively assay dopaminergic neurons, their projections, glial cells, synapses, and oxidative stress. Rotenone infusion into the substantia nigra at all concentrations caused extensive damage and tissue necrosis, therefore of limited relevance for producing a Parkinson disease model. Infusion of 0.5 μg of rotenone targeting the medial forebrain bundle induced oxidative stress in dopaminergic neurons causing ongoing cell stress as defined by an elevation of stress granule and oxidative stress markers. This treatment resulted in the loss of tyrosine hydroxylase immunoreactive cells in the substantia nigra (p ≤ 0.01) and loss of tyrosine hydroxylase immunoreactive nerve fibres and synaptic specialisations in the striatum (p ≤ 0.01). The infusion of 0.5 μg of rotenone also caused an increase in astrocytes and microglial cells in the substantia nigra in comparison to control (p ≤ 0.01). We examined the time-dependent reduction of tyrosine hydroxylase-positive nerve fibres and cell bodies in the striatum and substantia nigra respectively, with a progressive reduction evident 60 days after infusion (p ≤ 0.01, p ≤ 0.05). Dopaminergic axons exposed to low-dose rotenone undergo oxidative stress, with a resultant ongoing loss of dopaminergic neurons, providing an animal model relevant to Parkinson disease.

A 7-year-old female presented with putaminal necrosis associated with hemidystonia. Cranial magnetic resonance imaging revealed bilateral putaminal lesions appearing as hypointense signals on T 1-weighted images and hyperintense signals on T 2-weighted images. After a differential diagnosis of basal ganglial degeneration was made, putaminal necrosis was diagnosed. Low doses of levodopa (0.5 mg/kg daily) were administered, but her clinical signs worsened. Positron emission tomography scanning with [ 18 F]-6-fluoro-L-dopa revealed asymmetric uptake and right-sided dominant decreases of [ 18 F]-6-fluoro-L-dopa uptake of the putamen. On the basis of these findings, standard doses of levodopa (10 mg/kg daily) were administered, and her clinical signs improved. These results suggest that hemidystonia is associated with a disturbance of the dopamine system.

Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN).

Objective: With the progressive aging of the human population, there is an inexorable decline in muscle mass, strength and function. Anabolic supplementation with testosterone has been shown to effectively restore muscle mass in both young and elderly men. In this study, we were interested in identifying serum factors that change with age in two distinct age groups of healthy men, and whether these factors were affected by testosterone supplementation. Methods: We measured the protein levels of a number of serum biomarkers using a combination of banked serum samples from older men (60 to 75 years) and younger men (ages 18 to 35), as well as new serum specimens obtained through collaboration. We compared baseline levels of all biomarkers between young and older men. In addition, we evaluated potential changes in these biomarker levels in association with testosterone dose (low dose defined as 125 mg per week or below compared to high dose defined as 300 mg per week or above) in our banked specimens. Results: We identified nine serum biomarkers that differed between the young and older subjects. These ageassociated biomarkers included: insulin-like growth factor (IGF1), N-terminal propeptide of type III collagen (PIIINP), monokine induced by gamma interferon (MIG), epithelial-derived neutrophil-activating peptide 78 (ENA78), interleukin 7 (IL-7), p40 subunit of interleukin 12 (IL-12p40), macrophage inflammatory protein 1β (MIP-1β), platelet derived growth factor β (PDGFβ) and interferon-inducible protein 10 (IP-10). We further observed testosterone dose-associated changes in some but not all age related markers: IGF1, PIIINP, leptin, MIG and ENA78. Gains in lean mass were confirmed by dual energy X-ray absorptiometry (DEXA). Conclusions: Results from this study suggest that there are potential phenotypic biomarkers in serum that can be associated with healthy aging and that some but not all of these biomarkers reflect gains in muscle mass upon testosterone administration.

Posttraumatic stress disorder (PTSD) is typically accompanied by acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but several studies have also used a challenge model to further assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. This paper reviews common methodology and research findings on HPA function in PTSD, and discusses the pathophysiological mechanisms underlying these findings. We reviewed the literature and selected all English-language, human subject, data driven, pharmacological and non-pharmacological challenge studies pertaining to the HPA axis, and in vitro leukocyte glucocorticoid receptor studies in adult PTSD subjects.

Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age.

Rationale  Mescaline is a nonselective serotonin receptor agonist. It has relatively delayed onset of action and prolonged duration. Mescaline attenuates various behavioral parameters in rats; however, no information is available about its pharmacokinetics in rats and its relation to the behavioral changes produced by the drug. Objectives  The present study evaluates the spontaneous locomotor activity and sensorimotor gating in relation to mescaline

Background: Neostigmine is a spinal analgesic that could be a useful adjunct. This study was conducted to evaluate the postoperative analgesic efficacy and the safety of two low doses of intrathecal (IT) neostigmine in patients undergoing knee arthroscopy under spinal bupivacaine anaesthesia. Methods: By using a double-blinded study design, 80 patients undergoing knee arthroscopy during spinal anaesthesia were divided into four groups: bupivacaine group (Group B) received 15 mg hyperbaric bupivacaine; bupivacaine + fentanyl group (Group BF) received 15 mg hyperbaric bupivacaine mixed with 25 g fentanyl; bupivacaine + neostigmine group 1 (Group BN1) received 15 mg hyperbaric bupivacaine mixed with 25 g neostigmine; bupivacaine + neostigmine group 2 (Group BN2) received 15 mg hyperbaric bupivacaine mixed with 35 g neostigmine. The postoperative visual analog scale (VAS) and the incidence of adverse effects were recorded for 24 h after administration of study drugs.

Despite the reported tolerance to a low dose of lactose, many lactose malabsorbers follow a rigorous lactose-free diet also avoiding lactosecontaining drugs. Up to now, only a few case reports have described the onset of gastrointestinal symptoms in lactose malabsorbers following the ingestion of these drugs. It has been suggested that capsules ⁄ tablets contain no more than 400 mg of lactose.

We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90-114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25-50 mg) or high (50-100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure <90 and <5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/1 occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a doubl...

inflammatory factor 1-3 . It reduces organ damage in animal models of sepsis, ischemic injury and stroke 1,4,5 and substantially reduces mortality in patients with severe sepsis 6 . It was not known whether APC acts as a direct cell survival factor or whether its neuroprotective effect 5,7 is secondary to its anticoagulant and anti-inflammatory effects 1-3 . We report that APC directly prevents apoptosis in hypoxic human brain endothelium through transcriptionally dependent inhibition of tumor suppressor protein p53, normalization of the pro-apoptotic Bax/Bcl-2 ratio and reduction of caspase-3 signaling. These mechanisms are distinct from those involving upregulation of the genes encoding the anti-apoptotic Bcl-2 homolog A1 and inhibitor of apoptosis protein-1 (IAP-1) by APC in umbilical vein endothelial cells 8,9 . Cytoprotection of brain endothelium by APC in vitro required endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), as did its in vivo neuroprotective activity in a stroke model of mice with a severe deficiency of EPCR 10 . This is consistent with work showing the direct effects of APC on cultured cells via EPCR and PAR-1 (ref. 9). Moreover, the in vivo neuroprotective effects of low-dose mouse APC seemed to be independent of its anti-coagulant activity. Thus, APC protects the brain from ischemic injury by acting directly on brain cells.

Neurocognitive impairment is a well-documented consequence of methamphetamine addiction. Not surprising, methamphetamine-associated neurocognitive impairment has been identified as an important target of treatment. Thus, this study sought to determine whether rivastigmine, an acetylcholinesterase inhibitor and cognition enhancing agent, could improve neurocognitive performance in a sample of longterm, high-dose methamphetamine addicts who were not seeking treatment at the time of enrollment in the study. This double-blind, placebo-controlled study evaluated whether a daily dose 0, 3, or 6 mg of rivastigmine, administered over six consecutive days, would enhance performance on measures of attention/ information processing speed, episodic memory, and executive/frontal lobe functioning relative to test performance at baseline. The results revealed that rivastigmine did not alter neurocognition in this cohort. There are a number of factors that may have mitigated the effects of rivastigmine in this particular study, including especially the short-term, low-dose treatment regimen utilized. The negative findings notwithstanding, the study serves as a springboard for future investigations that will examine whether other medications can alter neurocognition in methamphetamine dependent study participants.

Stromal cell-derived factor-1 (SDF-1) is a CXC chemokine that activates and directs the migration of leukocytes that have CXCR4, which is the unique receptor for SDF-1. Although SDF-1/CXCR4 interaction has been implicated in various inflammatory conditions, its role in modulating ...

Malathion exerts cholinergic effects at high doses. However, a consequence of low dose (non-cholinergic) exposure causes immunotoxicity and oxidative stress. Hence, this study was designed to find out (i) the cytotoxic and apoptotic effects of cholinergic and non-cholinergic doses of malathion using cultured peripheral blood mononuclear cells (PBMCs) and (ii) the role of GSH and HSP27 and (iii) protective effects of N-acetylcysteine (GSH inducer) and curcumin (HSP27 inducer). In low doses, malathion caused mild depletion of GSH, threefold increase in HSP27 level and a range bound cytotoxicity and apoptosis of PBMC. In contrast, cholinergic dose exposures caused severe GSH depletion and exhibited dose dependent cytotoxicity and necrosis without any significant effect on HSP27 levels. Curcumin increased the levels of HSP27 in PBMC only in presence of low doses and not at high doses of malathion. Both NAC and curcumin were able to prevent malathion-mediated apoptosis of PBMC effectively at non-cholinergic doses and at this concentration of malathion, HSP27 induction keeps apoptosis and GSH depletion under control. Also NAC and curcumin may act as potential therapeutic agents to prevent malathion-induced immunotoxicity.

Dexamethasone is one of a number of synthetic corticosteroids illegally used to promote growth in food-producing animals. Since these low-level drug cocktails evade detection by currently available http://mc.manuscriptcentral.com/tfac Email: fac@tandf.co.uk Food Additives and Contaminants peer-00722241, version 1significant decrease in the cortex: medulla ratio in the treated animals (p<0.0005). We can 43 conclude that this histological approach offers encouraging prospects as a screening method 44 to overcome current limitations in controlling growth promoter abuse. 45 46 47 48 Chemical analysis 126 Urine samples of 10 treated animals and 10 controls were collected when spontaneous 127 urination occurred, the day before the first administration, 10 days later, and the last day of 128 treatment; urine was also collected after the last treatments, 1, 2, 5 and 10 days later, and at 129 the slaughterhouse. Each sample, without preservative, was divided into 6 mL aliquots and 130 stored at -80 °C until use. 131 132 Sample preparation 133 Urine samples (5 mL) spiked with triamcinolone acetonide-d 6 used as the internal standard 134 (IS) were added with acetate buffer solution 1 M, pH=4.8 and β-glucuronidase-arylsulphatase 135 enzyme solution (Helix pomatia). The samples were then incubated for 12 h at 37°C,

To contribute to complete the knowledge of the underlying mechanisms of action involved in air pollution particulate matter (PM)induced cytotoxicity, an aerosol was collected in Dunkerque, a French seaside City heavily industrialized. In this work, we focused our attention on its physical and chemical characteristics, its cytotoxicity, and its role in the induction of the volatile organic compound (VOC) and/or polycyclic aromatic hydrocarbon (PAH)-metabolizing enzymes in human lung epithelial cells (A549). Size distribution showed that 92.15% of the collected PM were PM 2.5 and the specific surface area was 1 m 2 /g. Inorganic (i.e. Fe, Al, Ca, Na, K, Mg, Pb, etc.) and organic (i.e. VOC, PAH, etc.) chemicals were found in collected PM, revealing that much of them derived from wind-borne dust from the industrial complex and the heavy motor vehicle traffic. The thermal desorption study indicated that organic chemicals were not only adsorbed onto the surface but also highly incrusted in the structure of PM. The lethal concentrations at 10% and 50% of collected PM were 23.72 mg/mL (or 6.33 mg/cm 2 ) and 118.60 mg/mL (or 31.63 mg/cm 2 ), respectively. The VOC and/or PAH-coated onto PM induced significant increases in mRNA expressions of cytochrome P450 (cyp) 1a1, cyp2e1, cyp2f1, nadph quinone oxydo-reductase-1, and glutathione s-transferase-pi 1, versus controls. Hence, we concluded that the metabolic activation of the very low doses of VOC and/or PAH-coated onto the inorganic condensation nuclei from Dunkerque City's PM is one of the underlying mechanisms of action closely involved in its cytotoxicity in human lung epithelial cells.

Background: Scoliosis is present in 3-5% of the children in the adolescent age group, with a higher incidence in females. Treatment of adolescent idiopathic scoliosis is mainly dependent on the progression of the scoliotic curve. There is a close relationship between curve progression and rapid (spinal) growth of the patient during puberty. However, until present time no conclusive method was found for predicting the timing and magnitude of the pubertal growth spurt in total body height, or the curve progression of the idiopathic scoliosis. The goal of this study is to determine the predictive value of several maturity indicators that reflect growth or remaining growth potential, in order to predict timing of the peak growth velocity of total body height in the individual patient with adolescent idiopathic scoliosis. Furthermore, different parameters are evaluated for their correlation with curve progression in the individual scoliosis patient.

When treatment intent is to include breast and internal mammary lymph nodes (IMNs) in the clinical target volume (CTV), a significant volume of the heart may receive radiation, which may result in late morbidity. The value of conformal intensity-modulated radiation therapy (IMRT) to avoid heart dose was studied.Breast, IMNs, and normal tissues were contoured for 30 consecutive patients previously treated with RT after lumpectomy for left-sided breast cancer. Eleven-beam, conformal, inverse-planned IMRT plans were developed and compared with best standard plans. Conformity Index (CI), Homogeneity Index (HI), and doses to normal tissues were compared.Intensity-modulated RT significantly improved (two-sided paired t test) HI (0.95 vs. 0.74), CI (0.91 vs. 0.48), volume of the heart receiving more than 30 Gy (V30-heart) (1.7% vs. 12.5%), and volume of lung receiving more than 20-Gy (V20-left lung) (17.1% vs. 26.6%), all p < 0.001. The mean Healthy Tissue Volume (HTV = CT set – PTV) dose was similar between IMRT and best standard plans (6.0 and 6.9 Gy, respectively), but IMRT increased the volume of normal tissues receiving low-dose RT: V5-right lung (13.7% vs. 2.0%), V5-right breast (29.2% vs. 7.9%), and V5-HTV (31.7% vs. 23.6%), all p < 0.001. IMRT plans were generated in less than 60 min and treatment delivered in approximately 20 min, suggesting that this technique is clinically applicable.IMRT significantly improved conformity and homogeneity for plans when the breast + IMNs were in the CTV. Heart and lung volume receiving high doses were decreased, but more healthy tissue received low doses. A simple algorithm based on amount of heart included in the standard plan showed limited ability to predict the benefit from IMRT.

Many studies have explored the effects of immunotherapy, alone or in combination with conventional therapies, on both experimental and human cancers. Evidence has been provided that combined treatments with thymosin alpha 1 (T a 1) and low doses of interferon (IFN) or interleukin (IL)-2 are highly effective in restoring several immune responses depressed by tumor growth and/or cytostatic drugs. In addition, when combined with specific chemotherapy, they are able to increase the anti-tumor effect of chemotherapy while markedly reducing the general toxicity of the treatment. The advantages of using this combined chemo-immunotherapeutic approach in experimental and human cancers are reviewed in this issue. : S 0 1 9 2 -0 5 6 1 ( 0 0 ) 0 0 0 7 5 -8 E. Garaci et al.