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1.
Int J Environ Health Res ; 34(2): 719-731, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36652575

ABSTRACT

Health agencies recommend using hand sanitisers as protection against the coronavirus. Thus far, the emphasis on hand sanitiser studies is limited to an analysis of disinfectant content only. This study aims to provide an extended analysis of 60 off-the-shelf alcohol-based hand sanitisers by using gas chromatography to report on alcohol content and the presence of impurities, a recombinant yeast estrogen screen to assess estrogenic activity, and an investigation into labelling compliance with the South African National Standard. Fifty hand sanitisers had an alcohol content of ≥60% v/v alcohol; however, most contained skin irritants and substances that could harm human and environmental health. Estrogenic activity was detected in 29 hand sanitisers and none of the products complied with all the labelling requirements. Since off-the-shelf hand sanitisers in South Africa are not regulated and monitored, evidence-based public awareness programmes on hand sanitiser quality and safety should become a priority.


Subject(s)
COVID-19 , Hand Sanitizers , Humans , COVID-19/prevention & control , South Africa , Pandemics/prevention & control , Hand Sanitizers/chemistry , Ethanol/chemistry
2.
Epidemiol Infect ; 144(2): 413-24, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26112878

ABSTRACT

The control of Johne's disease requires the identification of Mycobacterium avium ssp. paratuberculosis (MAP)-positive herds. Boot swabs and liquid manure samples have been suggested as an easy-to-use alternative to sampling individual animals in order to diagnose subclinical Johne's disease at the herd level, but there is a need to evaluate performance of this approach in the field. Using a logistic regression model, this study aimed to calculate the threshold level of the apparent within-herd prevalence as determined by individual faecal culture, thus allowing the detection of whether a herd is MAP positive. A total of 77 boot swabs and 75 liquid manure samples were taken from 19 certified negative and 58 positive dairy herds. Faecal culture, three different polymerase chain reaction (PCR) methods and the combination of faecal culture with PCR were applied in order to detect MAP. For 50% probability of detection, a within-herd prevalence threshold of 1·5% was calculated for testing both matrices simultaneously by faecal culture and PCR, with the threshold increased to 4·0% for 90% probability of detection. The results encourage the use of boot swabs or liquid manure samples, or a combination both, for identifying MAP-positive herds and, to a certain extent, for monitoring certified Johne's disease-negative cattle herds.


Subject(s)
Cattle Diseases/epidemiology , Mycobacterium avium subsp. paratuberculosis/isolation & purification , Paratuberculosis/epidemiology , Animals , Cattle , Cattle Diseases/microbiology , Female , Germany/epidemiology , Logistic Models , Manure/microbiology , Paratuberculosis/microbiology , Prevalence , Real-Time Polymerase Chain Reaction/veterinary
3.
Ecotoxicol Environ Saf ; 93: 171-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23669339

ABSTRACT

Water quality has deteriorated in the upper Olifants River system, South Africa, as a result of land use activities which include mining, agriculture and industries. A health risk assessment was conducted from 2009 to 2011 in the catchment to determine the possible risks local communities face from various pollutants such as microbials, heavy metals and oestrogen in the river water and vegetation. Aluminium and manganese accumulated in plants and vanadium and aluminium concentrations found in selective water samples posed significant health risks when consumed. A quantitative microbial risk assessment revealed that the combined risk of infection ranged from 1 to 26 percent with the Norovirus posing the overall greatest health risk. The anticipated disability adjusted life years resulting from drinking untreated water from these sites are in the order of 10,000 times greater than what is considered acceptable. The oestradiol activity, caused by endocrine disrupting compounds in the water, measured above the trigger value of 0.7ngL(-1). Impoverished communities in the area, who partially depend on river water for potable and domestic use, are exposed to immune-compromising metals that increase their probability of infection from waterborne diseases caused by the excess microbial pathogens in the contaminated surface water.


Subject(s)
Environmental Exposure/statistics & numerical data , Rivers/chemistry , Water Pollutants, Chemical/analysis , Water Pollution, Chemical/statistics & numerical data , Agriculture , Endocrine Disruptors/analysis , Environment , Humans , Mining , Public Health , Risk Assessment , Rivers/microbiology , South Africa , Water Microbiology
4.
Z Gastroenterol ; 51(3): 278-86, 2013 Mar.
Article in German | MEDLINE | ID: mdl-23299901

ABSTRACT

The introduction of the G-DRG reimbursement system has greatly increased the pressure to provide cost effective treatment in German hospitals. Reimbursement based on diagnosis-related groups, which requires stratification of costs incurred is still not sufficiently discriminating the disease severity and severity in relation to the intensive costs in gastroenterology. In a combined retrospective and prospective study at a tertial referral centre we investigated whether this also applies for decompensated liver cirrhosis. In 2006, 64 retrospective cases (age 57 ± 12.9; ♂ 69.2 %, ♀ 29.8 %) with decompensated liver cirrhosis (ICD code K76.4) were evaluated for their length of hospitalisation, reimbursement as well as Child and MELD scores. In 2008, 74 cases with decompensated liver cirrhosis were treated in a prospective study according to a standardised and evidence-based clinical pathway (age 57 ± 12.2; 73 % ♂, ♀ 27 %). Besides a trend in the reduction of length of hospital stay (retrospective: 13.6 ± 8.6, prospective 13.0 ± 7.2, p = 0.85) overall revenues from patients treated according to a evidence-based clinical pathway were lower than the calculated costs from the InEK matrix. Costs of medication as a percentage of reimbursement amount increased with increasing severity. In both years we could demonstrate an inverse correlation between daily reimbursement and disease severity which precluded cost coverage. For the cost-covering hospital treatment of patients with decompensated liver cirrhosis an adjustment of the DRG based on clinical severity scores such as Child-Pugh or MELD is warranted, if evidence-based treatment standards are to be kept.


Subject(s)
Critical Pathways/economics , Evidence-Based Medicine/economics , Health Care Costs/statistics & numerical data , Hospitalization/economics , Liver Cirrhosis/economics , Liver Cirrhosis/therapy , Evidence-Based Medicine/methods , Female , Germany/epidemiology , Hospitalization/statistics & numerical data , Humans , Inpatients/statistics & numerical data , Liver Cirrhosis/epidemiology , Male , Middle Aged , Prevalence , Risk Factors
5.
J Fish Biol ; 83(1): 39-51, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23808691

ABSTRACT

This study evaluated the diet and feeding selectivity of the catfish Imparfinis mirini in streams with different degrees of urbanization and the effect of rainfall on the availability of prey. The diet was based especially on Chironomidae and Trichoptera. Significant spatial differences in diet were found between the streams; the diet of the fish was similar in the rural and peri-urban streams, and differed from that in the urban stream. Seasonality was an unimportant factor affecting the species' diet, which did not differ significantly between the rainy and dry periods in any of the streams. Fish from the urban stream fed more according to what was available in the environment, while fish from the peri-urban and rural streams showed higher degrees of selectivity. The results indicate that environmental conditions influenced the diet and prey selection of this species in response to the differences in diversity and abundance of the food organisms. They indicate that trophic studies of benthivorous fishes, such as I. mirini, may represent an alternative way to assess human effects on streams.


Subject(s)
Catfishes , Diet , Feeding Behavior , Rivers , Urbanization , Animals
6.
Eur J Trauma Emerg Surg ; 48(3): 2081-2088, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34689226

ABSTRACT

PURPOSE: Emergency departments are frequently confronted with traumatic dental injuries (TDIs). The prognosis of the injured tooth is related to early dental trauma management. For this reason, physicians must be familiar with the appropriate management of TDI. This study aimed to investigate the knowledge and skills of German emergency physicians regarding TDI. METHODS: An electronic questionnaire was sent to 438 emergency departments throughout Germany. Four hundred and twenty seven questionnaires were evaluated and included in the analysis. The survey contained questions about physician characteristics and assessed their knowledge and skills of managing dental trauma. For statistical analysis, the Kruskal-Wallis, Mann-Whitney U test or ANOVA test was used as appropriate. Rank correlations were performed with the Spearman's rank correlation. RESULTS: Out of 427 participants, 256 (59.95%) stated they had no or insufficient knowledge, and 266 (71.12%) stated they had no skills in dental trauma management. Almost 76% of the participants had no previous knowledge of dentistry. Only 7.28% knew the right procedure for replanting an avulsed tooth. Just 26.06% would choose the right medium for temporary tooth storage. Having a dentist in the family (p = 0.0074) or clinical exposure to patients with dental trauma (p = 0.0384) influenced the results of the knowledge score. CONCLUSION: The knowledge and skills in dental trauma management among German emergency physicians are generally inadequate. Targeted training courses are necessary to ensure early and adequate TDI treatment to reduce the resulting medical and societal costs as much as possible.


Subject(s)
Physicians , Tooth Avulsion , Tooth Injuries , Health Knowledge, Attitudes, Practice , Humans , Surveys and Questionnaires , Tooth Avulsion/therapy , Tooth Injuries/therapy
7.
Ann Oncol ; 22(4): 801-807, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20880998

ABSTRACT

BACKGROUND: Metabolic syndrome (MS) is a set of risk factors that includes obesity and insulin resistance and has been implicated in the development of prostate cancer. Its impact on androgen deprivation therapy (ADT) efficacy has not been studied. PATIENTS AND METHODS: Retrospective study of prostate cancer patients seen from 1998 to 2005 in a medical oncology clinic. MS, as defined by modified Adult Treatment Panel III criteria, was assessed at the time of initiation of ADT. The study end points were time to prostate-specific antigen (PSA) progression and overall survival (OS) from time of starting ADT. RESULTS: Eighty-two patients treated with ADT and data to assess for presence of MS were identified. Median age in men with and without MS was 70 years and 49% of the patients evaluated met criteria for MS. Median time to PSA progression for patients with MS was 16 versus 36 months without MS (P=0.003). The median OS for patients with MS was 36.5 months after commencing ADT compared with 46.7 months for those patients without MS (P=0.061). CONCLUSIONS: This preliminary data suggest that MS is a risk factor for earlier development of castration-resistant prostate cancer and support the need for a prospective evaluation of this finding.


Subject(s)
Androgen Antagonists/therapeutic use , Metabolic Syndrome/chemically induced , Orchiectomy , Prostatic Neoplasms/therapy , Aged , Aged, 80 and over , Androgen Antagonists/adverse effects , Androgens , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Retrospective Studies , Risk Factors
8.
Transpl Infect Dis ; 13(3): 222-36, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21585633

ABSTRACT

BACKGROUND: Reactivation of cytomegalovirus (CMV) is a major cause of morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). In healthy individuals, virus-specific T cells (CMV-CTL) control the reactivation of latent CMV. The monitoring of virus-epitope-binding CD8(+) T cells using major histocompatibility complex-I-peptide complexes (tetramers) has recently been established, allowing assessment of the reconstitution of CMV-CTL post HSCT. PATIENTS AND METHODS: In order to study immune reconstitution and reactivation control through CMV-CTL, we regularly monitored all patients undergoing allogeneic HSCT in our department for 2 years, who matched at least 1 of 6 commercially available tetramers for common human leukocyte antigen (HLA) types. To verify risk factors for CMV reactivations in our cohorts, clinical characteristics of all patients transplanted within the last 10 years were included in statistical analyses determining the relative risk for single and recurrent CMV reactivations. RESULTS: As expected, CMV serostatus, HLA match, and donor source significantly influenced the risk of recurrent CMV reactivation. Applying CMV-CTL tetramer monitoring for 2 years allowed the monitoring of 114 (85%) of 134 patients, by testing a set of tetramers representing 6 epitopes from 3 different CMV proteins. The presence of CMV-CTL before day + 50 and their expansion post reactivation seem to protect against recurrent CMV reactivations. The mean number of CMV-CTL by day +100 was >5-fold higher in the recipient CMV-positive/donor-positive (R +/D +) group (91/µL) compared with the R +/ D- (13/µL) and the R -/D +(2/µL) group. Seventy-nine percent of patients from the R +/D + setting recovered >10 CMV-CTL per µL by day + 100, while almost 50% of the other groups failed to mount a CMV-specific response by that time (R +/D -: 58%; R -/D +: 43%). CONCLUSION: Tetramer monitoring can help to predict (recurrent) CMV reactivation and is a useful approach to monitor individual patients with increased risk for recurrent reactivation post HSCT; thus, it could help to identify patients in need of adoptive transfer of CMV-CTL or to optimize the use of antiviral drugs.


Subject(s)
Cytomegalovirus/physiology , Hematopoietic Stem Cell Transplantation/adverse effects , Histocompatibility Antigens Class I/immunology , Immune Reconstitution Inflammatory Syndrome/immunology , Multiprotein Complexes/immunology , Peptides/immunology , Virus Activation/physiology , Adult , CD8-Positive T-Lymphocytes/immunology , Cohort Studies , Cytomegalovirus/immunology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Female , Humans , Male , Middle Aged , Recurrence , Risk Factors , Transplantation, Homologous/adverse effects
9.
Anaesthesist ; 60(11): 995-1001, 2011 Nov.
Article in German | MEDLINE | ID: mdl-21918824

ABSTRACT

OBJECTIVE: Epidural regional analgesia is still recommended as the gold standard for obstetric analgesia due to its high efficacy and less depressing effects to the central nervous system. However, if absolute or relative contraindications for a regional anesthetic technique are present, there is a need for an effective and safe alternative. This survey investigates the current use of intravenous opioids, with a focus on remifentanil as patient-controlled intravenous analgesia (PCIA), in obstetrics in German hospitals. METHODS: A questionnaire was sent to 930 anesthesia units. Data were collected and analyzed using SPSS statistical package (PASW Statistics 18.0). The questionnaire requested statistics on births, the existing alternative labor analgesic techniques, intramuscular or intravenous opioids, PCIA or other options. Furthermore, the questions focused on details regarding the use of intravenous opioids in conjunction with PCIA techniques. RESULTS: Replies were received from 343 anesthetic departments (response rate 37%) and 281 clinics had an obstetric department and were included for further analysis. All clinics provided a 24 h epidural service and the most commonly used opioids were pethidine (19%), meptazinol (17%) and piritramide (16%) for intermittent intravenous/intramuscular administration. Only 0.9% of the clinics offered nitrous oxide as an alternative analgesic technique and 22 (8%) of the responding anesthetic departments offered PCIA. Remifentanil was the most popular choice in conjunction with PCIA (68%) for labor analgesia. Most hospitals offering PCIA continuously monitor oxygen saturation (91%) and the blood pressure (95%), whereas continuous electrocardiograms (18%) and clinical observation of the respiratory frequency (19%) were less commonly reported. However, most clinics offered one-to-one nursing for the parturient using an opioid PCIA. CONCLUSIONS: This survey revealed that pethidine, meptazinol and piritramide are the most common opioids for opioid-based systemic labor pain relief in Germany. If PCIA is offered, remifentanil is the most popular opioid. However, only a few clinics are routinely using PCIA for obstetric analgesia. Furthermore the study showed that the current monitoring standards seem to have room for improvement with respect to safe administration of an opioid PCIA. The safety standards require continuous observation of the oxygen saturation, the possibility for oxygen supply, one-to-one nursing for a close clinical observation of the mother and the presence of an anesthetist during the initial titration phase to safely apply this technique. Applying these safety standards PCIA may prove a useful alternative for central neuraxial labor analgesia in those women who either do not want, cannot have or do not need epidural analgesia.


Subject(s)
Analgesia, Obstetrical/methods , Analgesics, Opioid , Piperidines , Adult , Analgesia, Epidural , Analgesia, Patient-Controlled , Analgesics, Opioid/administration & dosage , Drug Utilization , Electrocardiography , Female , Germany , Health Care Surveys , Humans , Meperidine/administration & dosage , Meptazinol , Monitoring, Physiologic , Oxygen/blood , Piperidines/administration & dosage , Pirinitramide/administration & dosage , Pregnancy , Remifentanil , Surveys and Questionnaires
10.
Adv Pharmacol ; 92: 521-553, 2021.
Article in English | MEDLINE | ID: mdl-34452696

ABSTRACT

Male sex determination and sexual differentiation occur between 6-12 weeks of gestation. During the "male programming window" the fetal testes start to produce testosterone that initiates the development of the male reproductive tract. Exposure to endocrine disrupting chemicals (EDCs) able to mimic or disrupt steroid hormone actions may disrupt testicular development and adversely impact reproductive health at birth, during puberty and adulthood. The testicular dysgenesis syndrome (TDS) occurs as a result inhibition of androgen action on fetal development preceding Sertoli and Leydig cell dysfunction and may result from direct or epigenetic effects. Hypospadias, cryptorchidism and poor semen quality are elements of TDS, which may be considered a risk factor for testicular germ cell cancer (TGCC). Exposure to estrogen or estrogenic EDCs results in developmental estrogenization/estrogen imprinting in the rodent for prostate cancer (PCa). This can disrupt prostate histology by disorganization of the epithelium, prostatic intraepithelial neoplasia (PIN) lesions, in particular high-grade PIN (HGPIN) lesions which are precursors of prostatic adenocarcinoma. These defects persist throughout the lifespan of the animal and later in life estrogen exposure predispose development of cancer. Exposure of pregnant dams to vinclozolin, a competitive anti-androgen, and results in prominent, focal regions of inflammation in all exposed animals. The inflammation closely resembles human nonbacterial prostatitis that occurs in young men and evidence indicates that inflammation plays a central role in the development of PCa. In conclusion, in utero exposure to endocrine disrupters may predispose to the development of TDS, testicular cancer (TCa) and PCa and are illustrations of Developmental Origins of Health and Disease (DOHaD).


Subject(s)
Endocrine Disruptors , Gonadal Dysgenesis , Testicular Neoplasms , Adult , Animals , Endocrine Disruptors/toxicity , Female , Humans , Male , Pregnancy , Semen Analysis , Testicular Neoplasms/chemically induced
11.
Ann Oncol ; 20(12): 1971-6, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19605506

ABSTRACT

BACKGROUND: No standard therapy exists for post-docetaxel castrate-resistant prostate cancer (CRPC) patients. This trial aimed to determine the safety and efficacy of pemetrexed in post-docetaxel CRPC patients. MATERIALS AND METHODS: CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out. RESULTS: Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy. CONCLUSIONS: Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.


Subject(s)
Antineoplastic Agents/therapeutic use , Glutamates/therapeutic use , Guanine/analogs & derivatives , Orchiectomy , Prostatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Glutamates/adverse effects , Guanine/adverse effects , Guanine/therapeutic use , Humans , Male , Membrane Transport Proteins/genetics , Middle Aged , Mutation , Neoplasm Metastasis , Pemetrexed , Pharmacogenetics , Polymorphism, Genetic , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Survival Analysis
12.
Hum Reprod ; 24(10): 2429-38, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19608568

ABSTRACT

BACKGROUND: There is mounting evidence that deteriorated semen quality may be associated with increased serum concentration of 1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane (DDT) and its metabolites. The problem is exacerbated in situations where DDT is the only resource available to control malaria mosquitoes and DDT metabolite plasma concentration can reach 1000-fold the level found in other populations. There are limited and contradictory epidemiological data on whether DDT/dichlorodiphenyl-dichloroethylene (DDE) can also damage sperm DNA. Therefore, there is a need to investigate the possible adverse effects on human sperm genetic integrity in a sufficiently large study population with adequate exposure contrasts, especially in the high exposure range. METHODS: We conducted a cross-sectional study, recruiting 209 young males from three communities in an endemic malaria area where DDT is sprayed annually. Blood plasma p,p'-DDT and its metabolite p,p'-DDE levels were measured and expressed as lipid adjusted p,p'-DDT and p,p'-DDE values. The sperm chromatin structure assay and Aniline Blue test were used to assess sperm DNA/chromatin integrity. RESULTS: The lipid adjusted p,p'-DDT mean (+/-SD) and median concentrations were 109.2 (+/-106.6) and 83.9 microg/g, respectively; and the lipid adjusted p,p'-DDE mean (+/-SD) and median concentrations were 246.2 (+/-218.5) and 177.8 microg/g, respectively. The results point to a weak association between DDT/DDE plasma concentration and the incidence of sperm with chromatin defects. CONCLUSIONS: The results suggest that non-occupational environmental DDT exposure may have a negative impact on sperm chromatin integrity in young South African males.


Subject(s)
Chromatin/drug effects , DDT/toxicity , Spermatozoa/drug effects , Adolescent , Adult , Cross-Sectional Studies , DDT/blood , DNA Damage , DNA Fragmentation , Dichlorodiphenyl Dichloroethylene/blood , Flow Cytometry , Humans , Male , Semen Analysis , South Africa
13.
Mini Rev Med Chem ; 9(5): 627-3, 2009 May.
Article in English | MEDLINE | ID: mdl-19456293

ABSTRACT

Proteome analysis, the key technology for biomarker discovery, continues to gain importance in clinical diagnosis and follow-up. In this review we describe proteome analysis in the context of allogeneic, hematopoietic stem cell transplantation concentrating on capillary electrophoresis coupled on-line to mass spectrometry.


Subject(s)
Electrophoresis, Capillary/methods , Hematology , Mass Spectrometry/methods , Online Systems , Proteome/analysis , Diagnosis , Humans
14.
J Fish Biol ; 75(1): 75-86, 2009 Jul.
Article in English | MEDLINE | ID: mdl-20738483

ABSTRACT

The relative abundance and size of prey fish in the stomachs of the predator Acestrorhynchus pantaneiro were compared with those recorded in the field to estimate prey selection. Fish samples were taken monthly in the Manso Reservoir (State of Mato Grosso, Brazil) immediately after the impoundment, from March 2000 to February 2001 (period I) and from March 2003 to February 2004 (period II). In period I, the small relative dominance of the prey in the environment seemed to have lead to random foraging. In period II, however, when the forage fish Moenkhausia dichroura was dominant in the environment, the predator shifted its diet, foraging mainly on this prey. Species with short relative body depth were positively selected. The prey size classes between 30 and 49 mm, and 50 and 69 mm standard length (L(S)) were the most abundant in the environment. Small prey were predominantly selected by A. pantaneiro. Even when a given prey or prey size was predominant in the environment, A. pantaneiro was a selective predator and maintained its preferences associated to prey type and L(S), although it consumed the most abundant resource.


Subject(s)
Fishes/physiology , Food Preferences/physiology , Predatory Behavior , Animals , Body Size/physiology , Brazil , Feeding Behavior/physiology , Fresh Water , Tropical Climate
15.
Physiol Int ; 106(1): 29-38, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30888218

ABSTRACT

PURPOSE: We previously found that homocysteine (Hcy)-induced apoptosis in endothelial cells coincided with increased NADPH oxidase (NOX) activity. In addition, in ischemic endothelial cells present in the heart, we showed that loss of serine protease dipeptidyl peptidase IV (DPP4) expression was correlated with induction of tissue factor (TF) expression. Since Hcy can initiate thrombosis through the induction of TF expression, in this study, we evaluated whether the inverse relation of TF and DPP4 is also Hcy-dependent and whether NOX-mediated reactive oxygen species (ROS) is playing a role herein. METHODS: Human umbilical vein endothelial cells (HUVECs) were incubated with 2.5 mM Hcy for 3 and 6 h. The effects of Hcy on DPP4 and TF expression and NOX2/p47phox-mediated nitrotyrosine (ROS) production were studied using digital-imaging microscopy. RESULTS: In HUVECs, high levels of Hcy showed a significant increase of TF expression and a concomitant loss of DPP4 expression after 6 h. In addition, NOX subunits NOX2 and p47phox were also significantly increased after 6 h of Hcy incubation and coincided with nitrotyrosine (ROS) expression. Interestingly, inhibition of NOX-mediated nitrotyrosine (ROS) with the use of apocynin not only reduced these effects, but also counteracted the effects of Hcy on TF and DPP4 expression. CONCLUSION: These results indicate that the inverse relation of TF and DPP4 in endothelial cells is also Hcy-dependent and related to NOX activity.


Subject(s)
Dipeptidyl Peptidase 4/metabolism , Homocysteine/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , NADPH Oxidases/metabolism , Thromboplastin/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Oxidation-Reduction , Reactive Oxygen Species/metabolism
16.
Sci Adv ; 5(4): eaaw2869, 2019 04.
Article in English | MEDLINE | ID: mdl-31016243

ABSTRACT

The Global Deal for Nature (GDN) is a time-bound, science-driven plan to save the diversity and abundance of life on Earth. Pairing the GDN and the Paris Climate Agreement would avoid catastrophic climate change, conserve species, and secure essential ecosystem services. New findings give urgency to this union: Less than half of the terrestrial realm is intact, yet conserving all native ecosystems-coupled with energy transition measures-will be required to remain below a 1.5°C rise in average global temperature. The GDN targets 30% of Earth to be formally protected and an additional 20% designated as climate stabilization areas, by 2030, to stay below 1.5°C. We highlight the 67% of terrestrial ecoregions that can meet 30% protection, thereby reducing extinction threats and carbon emissions from natural reservoirs. Freshwater and marine targets included here extend the GDN to all realms and provide a pathway to ensuring a more livable biosphere.


Subject(s)
Biodiversity , Conservation of Natural Resources , Earth, Planet , Ecosystem , Models, Biological , Adaptation, Physiological , Animals , Climate Change , Humans
17.
Urol Oncol ; 36(7): 345, 2018 07.
Article in English | MEDLINE | ID: mdl-29880459

ABSTRACT

BACKGROUND: Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. MATERIALS AND METHODS: Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. RESULTS: A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. CONCLUSION: The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.


Subject(s)
Carcinoma, Transitional Cell/surgery , Neoadjuvant Therapy , Carcinoma in Situ , Cystectomy , Humans , Prognosis , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/surgery
19.
Cancer Res ; 37(3): 879-83, 1977 Mar.
Article in English | MEDLINE | ID: mdl-837383

ABSTRACT

Radiofrequency electromagnetic fields at 13.56 MHz were used to heat locally EMT-6 sarcomas and KHJJ carcinomas in BALB/cKa mice. Temperature profiles obtained in tumors during treatment showed uniform temperature distribution throughout the tumor volume with no systemic hyperthermia. Temperature could be maintained at a stable level throughout treatment by adjustment of power. Tumors were treated at 43 degrees, 43-5 degrees, and 44 degrees, for 5, 10, 20, 30, and 40 min. The EMT-6 tumor was highly sensitive to cure by radiofrequency heating: a 5-min exposure at 44 degrees resulted in cure of almost 50% of the tumors. Cure rate was a function of temperature and of duration of exposure. The KHJJ carcinoma was somewhat more resistant to cure by radiofrequency heating, although most of the animals treated at 43.5 degrees or above were cured of their tumors. In an effort to explain the remarkable effectiveness of radiofrequency heating, tumor cell survival studies were done on EMT-6 tumors treated in situ. Cell inactivation by radiofrequency heating was similar to that for hot water bath heating. However, direct cell killing cannot account for the observed cures, and an additional mechanism must be responsible for tumor eradication.


Subject(s)
Hyperthermia, Induced/methods , Neoplasms, Experimental/therapy , Animals , Cell Survival , Electromagnetic Phenomena , Hyperthermia, Induced/instrumentation , In Vitro Techniques , Mammary Neoplasms, Experimental/pathology , Mammary Neoplasms, Experimental/therapy , Mice , Mice, Inbred BALB C , Neoplasms, Experimental/pathology , Radio Waves , Sarcoma, Experimental/pathology , Sarcoma, Experimental/therapy , Temperature , Time Factors
20.
FEBS Lett ; 462(1-2): 159-60, 1999 Nov 26.
Article in English | MEDLINE | ID: mdl-10580111

ABSTRACT

Commonly applied genotyping of transgenic mice involves using tail or ear biopsies which may cause discomfort to the animal. We tested the possibility of polymerase chain reaction (PCR)-based mouse genotyping using stool specimens from three transgenic mouse lines that overexpress 10-18 transgene copies of human keratin polypeptide 18, as compared to genotyping using tail biopsies. Stool specimens were obtained with ease and provided easy detection of the human transgene product. The method was also able to detect endogenous mouse actin and keratin genes which presumably are present at two copies each. Nested PCR was not necessary for genotyping using stool-derived genomic material but did increase the relative magnitude of the signal obtained. The non-invasive genotyping method described herein offers a reproducible, sensitive and effective modality that could replace invasive tissue sampling procedures currently used to test thousands of genetically altered mice.


Subject(s)
Feces/chemistry , Mice, Transgenic/genetics , Polymerase Chain Reaction/methods , Animals , Biopsy/methods , Genotype , Humans , Keratins/analysis , Keratins/genetics , Mice
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