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1.
Water Sci Technol ; 87(7): 1630-1642, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37051787

RESUMO

The advancing digitalisation is one of the great challenges of our times. Related activities also concern the wastewater sector. In the field of building construction, one emerging approach is building information modelling (BIM). The presented work investigates to which extent BIM practices have already found their way to wastewater management, and what kind of benefits and constraints are incorporated. Information is collected by means of a literature review and international expert surveys. Results indicate that several BIM-related key elements are already well established in the sector, but not necessarily in the intended manner. Consequently, the digital transition in the wastewater sector is not about replacing existing procedures and techniques but to rethink and optimise them. This primarily concerns data and information management in combination with the application of digital tools. Furthermore, wastewater management requires more integrated approaches, involving interdisciplinary/collaborative concepts and life cycle perspectives. Appropriate change management is necessary to give support and guidance to employees during the transition process. Furthermore, also from the political side, a clear definition and communication of the pursued digital vision is important. This article aims at stimulating discussion and research to optimise wastewater management from the digital perspective.


Assuntos
Águas Residuárias
2.
J Environ Manage ; 265: 110507, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32292170

RESUMO

Multiple pressures as urbanization, densification and climate change lead to the need for adaptation of sewer systems within urban environments. To increase the adaptive capacity of stormwater management systems, there is a shift towards decentralized nature-based solutions (NBS). Especially in densely built areas the availability of land can be a limiting factor for the implementation of NBS. To consider the spatial framework conditions in planning we developed an integrated modelling framework for prioritizing sites for NBS implementation for stormwater management within built urban structures. The implementation potential of NBS from a settlement structure model and a street typology model are combined with the discharge reduction potential from a sewer model. In effectiveness matrices priorities for stormwater management sites for individual NBS are identified. This modelling framework offers a transparent and flexible approach to decision making for the implementation of NBS.


Assuntos
Chuva , Urbanização , Mudança Climática
3.
Water Sci Technol ; 78(11): 2239-2246, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30699075

RESUMO

It is widely accepted that partial nitrification by ANAMMOX has the potential to become one of the key processes in wastewater treatment. However, large greenhouse gas emissions have been panobserved in many cases. A novel mesh separated reactor, developed to allow continuous operation of deammonification at smaller scale without external biomass selection, was compared to a conventional single-chamber deammonification sequencing batch reactor (SBR), where both were equally-sized pilot-scale reactors. The mesh reactor consisted of an aerated and an anoxic zone separated by a mesh. The resulting differences in the structure of the microbial community were detected by next-generation sequencing. When both systems were operated in a sequencing batch mode, both systems had comparable nitrous oxide emission factors in the range of 4% to 5% of the influent nitrogen load. A significant decrease was observed after switching from sequencing batch mode to continuous operation.


Assuntos
Poluentes Atmosféricos/análise , Reatores Biológicos , Óxido Nitroso/análise , Eliminação de Resíduos Líquidos/métodos , Nitrificação , Telas Cirúrgicas , Águas Residuárias
4.
Reproduction ; 142(3): 427-37, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21730112

RESUMO

The role of innate cells and their receptors within the male genital tract remains poorly understood. Much less is known about the relative contribution of different genital tract cells such as epithelial/stromal cells and resident leucocytes. In this study, we examined innate immune responses to Chlamydia trachomatis by prostate epithelial/stromal cells and prostate resident leucocytes. Murine prostate primary cultures were performed and leucocyte and epithelial/stromal cells were sorted based on surface protein expression of CD45 by magnetism-activated cell sorting or fluorescence-activated cell sorting. Prostate derived CD45- and CD45+ cells were infected with C. trachomatis and chemokine secretion assayed by ELISA. Similar experiments were performed using prostate CD45+ and CD45- cells from myeloid differentiation factor 88 (Myd88(-/-)) mice or toll-like receptor (Tlr2(-/-)) and Tlr4(mutant) double-deficient mice. Moreover, a TLR-signalling pathway array was used to screen changes in different genes involved in TLR-signalling pathways by real-time PCR. Prostate derived CD45- and CD45+ cells responded to chlamydial infection with the production of different chemokines. Both populations expressed genes involved in TLR signalling and required to respond to pathogen-associated molecular patterns and to C. trachomatis infection. Both populations required the adaptor molecule MYD88 to elicit chemokine response against C. trachomatis. TLR2-TLR4 was essential for chemokine production by CD45+ prostate derived cells, but in their absence, CD45- cells still produced significant levels of chemokines. We demonstrate that C. trachomatis is differentially recognised by prostate derived CD45+ and CD45- cells and suggest that diverse strategies are taking place in the local microenvironment of the host in response to the infection.


Assuntos
Quimiocinas/metabolismo , Infecções por Chlamydia/patologia , Chlamydia trachomatis/fisiologia , Antígenos Comuns de Leucócito/metabolismo , Próstata/metabolismo , Próstata/patologia , Animais , Células Cultivadas , Quimiocina CXCL1/metabolismo , Infecções por Chlamydia/genética , Infecções por Chlamydia/metabolismo , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/fisiologia , Cultura Primária de Células , Próstata/microbiologia , Regulação para Cima
5.
Trials ; 22(1): 84, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482890

RESUMO

BACKGROUND: The lack of approved treatments for the majority of rare diseases is reflective of the unique challenges of orphan drug development. Novel methodologies, including new functionally relevant endpoints, are needed to render the development process more feasible and appropriate for these rare populations and thereby expedite the approval of promising treatments to address patients' high unmet medical need. Here, we describe the development of an innovative master protocol and primary outcome assessment to investigate the modified amino acid N-acetyl-L-leucine (Sponsor Code: IB1001) in three separate, multinational, phase II trials for three ultra-rare, autosomal-recessive, neurodegenerative disorders: Niemann-Pick disease type C (NPC), GM2 gangliosidoses (Tay-Sachs and Sandhoff disease; "GM2"), and ataxia telangiectasia (A-T). METHODS/DESIGN: The innovative IB1001 master protocol and novel CI-CS primary endpoints were developed through a close collaboration between the Industry Sponsor, Key Opinion Leaders, representatives of the Patient Communities, and National Regulatory Authorities. As a result, the open-label, rater-blinded study design is considerate of the practical limitations of recruitment and retention of subjects in these ultra-orphan populations. The novel primary endpoint, the Clinical Impression of Change in Severity© (CI-CS), accommodates the heterogenous clinical presentation of NPC, GM2, and A-T: at screening, the principal investigator appoints for each patient a primary anchor test (either the 8-m walk test (8MWT) or 9-hole peg test of the dominant hand (9HPT-D)) based on his/her unique clinical symptoms. The anchor tests are videoed in a standardized manner at each visit to capture all aspects related to the patient's functional performance. The CI-CS assessment is ultimately performed by independent, blinded raters who compare videos of the primary anchor test from three periods: baseline, the end of treatment, and the end of a post-treatment washout. Blinded to the time point of each video, the raters make an objective comparison scored on a 7-point Likert scale of the change in the severity of the patient's neurological signs and symptoms from video A to video B. To investigate both the symptomatic and disease-modifying effects of treatment, N-acetyl-L-leucine is assessed during two treatment sequences: a 6-week parent study and 1-year extension phase. DISCUSSION: The novel CI-CS assessment, developed through a collaboration of all stakeholders, is advantageous in that it better ensures the primary endpoint is functionally relevant for each patient, is able to capture small but meaningful clinical changes critical to the patients' quality of life (fine-motor skills; gait), and blinds the primary outcome assessment. The results of these three trials will inform whether N-acetyl-L-leucine is an effective treatment for NPC, GM2, and A-T and can also serve as a new therapeutic paradigm for the development of future treatments for other orphan diseases. TRIAL REGISTRATION: The three trials (IB1001-201 for Niemann-Pick disease type C (NPC), IB1001-202 for GM2 gangliosidoses (Tay-Sachs and Sandhoff), IB1001-203 for ataxia telangiectasia (A-T)) have been registered at www.clinicaltrials.gov (NCT03759639; NCT03759665; NCT03759678), www.clinicaltrialsregister.eu (EudraCT: 2018-004331-71; 2018-004406-25; 2018-004407-39), and https://www.germanctr.de (DR KS-ID: DRKS00016567; DRKS00017539; DRKS00020511).


Assuntos
Ataxia Telangiectasia , Gangliosidoses GM2 , Doenças Neurodegenerativas , Feminino , Humanos , Leucina , Masculino , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/tratamento farmacológico , Qualidade de Vida
6.
J Endocrinol Invest ; 33(7): 443-5, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20671407

RESUMO

BACKGROUND: Since its discovery, several distinct effects of pituitary adenylate cyclase activating polypeptide (PACAP) have been established - predominantly in animal studies - in the nervous system, various peripheral organs as well as in the endocrine regulation. It is unknown whether PACAP has any effect on human pregnancy regarding either utero-maternal or perinatal aspects of the gestation. AIM: We investigated alterations of PACAP38-like immunoreactivity (PACAP38-LI) in the human plasma throughout normal pregnancy, during and after delivery, and its level in the umbilical vessels, as well as in the peripheral blood of term healthy newborns. MATERIALS AND METHODS: A 2 ml blood sample was used for each test, PACAP38-LI was determined by radioimmunoassay. RESULTS: In the 2nd and 3rd trimester significant elevation was observed in the PACAP38-LI compared to the earlier gestation and non-pregnant conditions. During delivery its level significantly decreased and returned to the original values 3 days after birth. In the neonates PACAP38-LI level of the peripheral blood was similar to that of healthy adults, but umbilical arteries and veins contained significantly lower concentrations of PACAP38-LI. Besides, the levels were lower in the umbilical vein compared to the artery. CONCLUSIONS: PACAP38-LI levels show sensitive change during normal pregnancy and delivery. Our findings suggest that the fetal organs actively synthesize PACAP. Further investigations are required to elucidate the physiological importance of the alterations observed.


Assuntos
Recém-Nascido/sangue , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/sangue , Período Pós-Parto/sangue , Gravidez/sangue , Adulto , Feminino , Humanos , Parto/sangue , Segundo Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Artérias Umbilicais/química , Veias Umbilicais/química
7.
Physiol Int ; 107(1): 55-66, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32598332

RESUMO

Numerous studies indicate that smoking during pregnancy exerts harmful effects on fetal brain development. The aim of this study was to determine the influence of maternal smoking during pregnancy on the early physical and neurobehavioral development of newborn rats. Wistar rats were subjected to whole-body smoke exposure for 2 × 40 min daily from the day of mating until day of delivery. For this treatment, a manual closed-chamber smoking system and 4 research cigarettes per occasion were used. After delivery the offspring were tested daily for somatic growth, maturation of facial characteristics and neurobehavioral development until three weeks of age. Motor coordination tests were performed at 3 and 4 weeks of age. We found that prenatal cigarette smoke exposure did not alter weight gain or motor coordination. Critical physical reflexes indicative of neurobehavioral development (eyelid reflex, ear unfolding) appeared significantly later in pups prenatally exposed to smoke as compared to the control group. Prenatal smoke exposure also resulted in a delayed appearance of reflexes indicating neural maturity, including hind limb grasping and forelimb placing reflexes. In conclusion, clinically relevant prenatal exposure to cigarette smoke results in slightly altered neurobehavioral development in rat pups. These findings suggest that chronic exposure of pregnant mothers to cigarette smoke (including passive smoking) results in persisting alterations in the developing brain, which may have long-lasting consequences supporting the concept of developmental origins of health and disease (DoHAD).


Assuntos
Comportamento Animal/efeitos dos fármacos , Doenças do Sistema Nervoso/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Fumar/efeitos adversos , Animais , Animais Recém-Nascidos , Peso Corporal , Modelos Animais de Doenças , Feminino , Masculino , Atividade Motora/fisiologia , Doenças do Sistema Nervoso/induzido quimicamente , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos , Ratos Wistar , Reflexo/fisiologia
8.
J Neurol ; 267(4): 1211-1220, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32002650

RESUMO

Cerebellar ataxias (CAs) represent a heterogeneous group of sporadic or inherited disorders. The clinical spectrum of CAs is continuously expanding. Our understanding of the mechanisms leading to the clinical deficits has improved over these last decades, in particular thanks to progress in genetics, neuroimaging and the advent of relevant animal models allowing the identification of the pathophysiological pathways leading to CAs. The rationale behind treatments is now established for most of the CAs encountered during daily practice worldwide. In this update, we will discuss the symptomatic, physical and occupational therapies now being trialled along with individualized exercises, and present key emerging issues on immune-mediated cerebellar ataxias, hereditary cerebellar ataxias. Finally, we will discuss novel therapeutic approaches, including cerebellar non-invasive stimulation and treatments acting on RNA/proteins. So far, no state-of-the art randomized placebo-controlled clinical trial has shown a convincing clinically relevant efficacy of any drug, with the exception of 4-aminopyridine for the symptomatic treatment of episodic ataxia type 2 and downbeat nystagmus (placebo-controlled trials).


Assuntos
Ataxia Cerebelar/terapia , Ataxia Cerebelar/genética , Ataxia Cerebelar/imunologia , Ataxia Cerebelar/metabolismo , Humanos
9.
Cancer Res ; 54(4): 1035-41, 1994 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-8313359

RESUMO

In this study, we investigated the effect of bombesin/GRP antagonist RC-3095 on the growth of CFPAC-1 human pancreatic cancer cells transplanted to nude mice or cultured in vitro. Nude mice bearing xenografts of the CFPAC-1 cell line received s.c. injections of RC-3095 (10 micrograms twice a day) or the vehicle (control) for 25 days. Chronic administration of RC-3095 inhibited the growth of CFPAC-1 tumors in nude mice as shown by a significant decrease in tumor volume throughout the period of treatment. Tumor volume doubling time was prolonged by RC-3095 treatment from 7.2 days to 10 days, and the tumor growth rate was decreased by 49%. In mice treated with RC-3095, the tumor growth delay time was 5.8 days. Treatment with RC-3095 decreased the final tumor weight by 37% and reduced DNA and protein contents in tumor tissues by 44 and 39.9%, respectively, compared to the controls. In cultures of the CFPAC-1 cell line, the addition of bombesin(1-14) (1 pM-0.1 microM) to the medium induced a dose-dependent increase in cell number. RC-3095 at 1 nM concentration effectively inhibited the bombesin-stimulated growth of CFPAC-1 cells in cultures. In the presence of 1 microM RC-3095 in the culture medium, the bombesin-induced growth of CFPAC-1 cells was totally suppressed. Bombesin was also shown to stimulate the DNA synthesis in CFPAC-1 cells in vitro as based on [3H]thymidine incorporation assay. When the cells were cultured in the presence of 1-100 nM bombesin, the uptake of [3H]thymidine by the cells was increased by 89-131%. RC-3095 inhibited both the basal and bombesin-stimulated DNA synthesis of CFPAC-1 cells. Addition of RC-3095 (10-100 nM) alone to the cultures caused a 39-40% decrease in the [3H]thymidine incorporation by the cells. Concomitant addition of RC-3095 (1 microM) and bombesin (1-100 nM) to the cultures induced a significant reduction in the uptake of [3H]thymidine by the cells compared to the values obtained with bombesin alone. Receptor binding assays showed the presence of two classes of specific binding sites for bombesin on CFPAC-1 cells, one with high affinity (Kd = 4.25 +/- 0.77 nM) and low capacity (Bmax = 0.268 +/- 0.052 pmol/10(6) cells) and the other with low affinity (Kd = 321.70 +/- 68.46 nM) and high capacity (Bmax = 3.991 +/- 0.374 pmol/10(6) cells).(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Antineoplásicos/uso terapêutico , Bombesina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Receptores da Bombesina/antagonistas & inibidores , Animais , Bombesina/antagonistas & inibidores , Bombesina/metabolismo , Bombesina/farmacologia , Bombesina/uso terapêutico , DNA de Neoplasias/análise , DNA de Neoplasias/biossíntese , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/análise , Transplante de Neoplasias , Neoplasias Pancreáticas/patologia , Fragmentos de Peptídeos/farmacologia
10.
Int J Oncol ; 6(6): 1165-72, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21556653

RESUMO

It has been demonstrated that bombesin/GRP antagonist D-Tpi(6),Leu(13)psi(CH2NH) Leu(14)-BN(6-14) (RC-3095) inhibits effectively the growth of pancreatic cancer and other tumors in experimental animals and in cell cultures. In an attempt to develop antagonists with still greater antitumor activity, several new pseudononapeptide bombesin/GRP antagonists containing C-terminal Leu psi(CH2N)Tac-NH2 have been synthesized in our laboratory. In this study, we investigated the ability of four Leu(13)psi(CH2N)Tac(14)-BN(6-14) antagonists to inhibit the binding of bombesin to specific receptors for bombesin/GRP on CFPAC-1 human pancreatic cancer cells. Receptor binding assays were performed by incubating CFPAC-1 cells (5x10(4) cells/well) with 0.5 nM [I-125]-Tyr(4)-bombesin in the absence or presence of (1 pM to 10 mu M) unlabeled bombesin, GRP(14-27) and various antagonists for 2 h at 22 degrees C. Displacement assays showed that antagonist D-Tpi(6),Leu(13)psi(CH2N)Tac(14)-BN(6-14) (RC-3910-II) with a similar structure to RC-3095, but a different C-terminal, had a binding affinity to CFPAC-1 cells 15 times higher than RC-3095. Three other antagonists, RC-3925-II, RC-3940-II and RC-3950-II contained the same C-terminal Leu psi(CH2N)Tac-NH2 as RC-3910-II, but had different N-terminal residues: D-Cpa, Hca and D-Phe, respectively. Among them, Hca(6),Leu(13)psi(CH2N)Tac(14)-BN(6-14) (RC-3940-II) showed the highest binding affinity to the receptors on CFPAC-1 cells, which was 50 times higher than that of RC-3095 or 3 times greater than RC-3910-II. Our findings suggest the merit of further investigation of pseudononapeptide bombesin/GRP antagonist RC-3940-II ind related analogs for a possible development of a new hormonal therapy for pancreatic cancer.

11.
Int J Oncol ; 6(5): 969-75, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-21556626

RESUMO

The effects of luteinizing hormone-releasing hormone (LH-RH), and LH-RH antagonist Cetrorelix, (SB-75, [Ac-D-Nal(2)(1),D-Phe(4-Cl)(2),D-Pal(3)(3),D-Cit(6),D-Ala(10)]LH-RH) on cell growth and the production of hCG and cAMP in JAR human choriocarcinoma cells were examined in vitro. Both LH-RH and its antagonist SE-75, at 1 mu g concentration, inhibited the growth of JAR cells in cultures. When SE-75 (1 mu M) was given in combination with different doses (0.1 nM to 1 mu M) of LH-RH, it was found that 0.1 nM LH-RH nullified the inhibitory effect of SE-75 on cell growth, however, the 100 nM and 1 mu M doses of LH-RH caused a greater inhibition of cell proliferation than SE-75 alone. Incubation with LH-RH slightly increased the hCG production and the cAMP release in the cultured tumor cells. SE-75 alone or in combination with LH-RH reduced the hCG as well as the cAMP release from JAR human choriocarcinoma cells; however, the magnitude of the decrease was smaller for hCG than for cAMP. The effect of different doses of LH-RH, administered simultaneously with 1 mu M SE-75, on the cAMP production, was similar to that on cell growth: 0.1 nM LH-RH in combination with 1 mu M SE-75 caused a smaller inhibition of cAMP than SE-75 alone. However, when LH-RH was given at concentrations from 1 nM to 1 mu M together with 1 mu M SE-75, we observed a greater inhibition of cAMP than after SE-75 alone. The presence of low affinity LH-RH receptors on JAR cells was also demonstrated and competitive binding studies showed that agonist D-Trp(6)-LH-RH and antagonist SE-75 could bind to these receptors. Our findings provide new information on the effect of LH-RH and antagonist SE-75 on the proliferation of JAR human choriocarcinoma cells and may offer a new insight on their mechanisms of action in the suppression of tumor cell growth and their influence on intracellular signal transduction pathways. Hormonal therapy based on Cetrorelix could be considered for the development of new approaches to treatment of patients with choriocarcinomas.

12.
Int J Oncol ; 6(3): 547-53, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21556569

RESUMO

The effects of bombesin/GRP antagonists RC-3095 and RC-3940-II on the in vitro proliferation of JAR human choriocarcinoma cells were evaluated. Antagonists RC-3095 and RC-3940-II effectively inhibited growth of cultured JAR cells, inducing a dose- and time-dependent decrease in the number of treated cells. RC-3940-II was more potent than RC-3095 in inhibiting the growth of JAR cells. Addition of RC-3940-II to JAR cell cultures significantly inhibited the cell proliferation at concentrations as low as 1 nM, while 10 nM RC-3095 was required for a similar effect. Receptor binding studies demonstrated the presence of a single class of binding sites for bombesin on JAR cells. RC-3940-II displaced [I-125]Tyr(4)-bombesin bound to the receptors. When JAR cells were cultured in the presence of 10 nM RC-3095 or RC-3940-II for 72 h, cAMP levels in the incubation medium were decreased by 70-80%, compared to the controls. These results suggest that bombesin/GRP antagonists RC-3095 and RC-3940-II inhibit the proliferation of JAR human chorionic adenocarcinoma cells in vitro and that these effects may involve intracellular cAMP pathway.

13.
J Cancer Res Clin Oncol ; 120(9): 519-28, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8045917

RESUMO

We investigated the effect of bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095 and other analogs on the growth of Hs746T human gastric cancer cells implanted in nude mice or cultured in vitro and on the binding of bombesin to its receptors. Nude mice bearing xenografts of the Hs746T cell line received s.c. injections of RC-3095 (10 micrograms twice daily) or the vehicle (control) for 21 days. Administration of antagonist RC-3095 inhibited the growth of Hs746T tumors. Treatment with RC-3095 produced a significant decrease in tumor volume, prolonged the tumor volume doubling time from 3.6 days to 5.1 days, and decreased the tumor growth rate by 76.9%. The tumor growth delay time in mice treated with RC-3095 was 2.8 days. Treatment with RC-3095 also decreased the final tumor weight by 88.3% and reduced DNA and protein contents in tumors by 91.5% and 89.5%, respectively, as compared to controls. The presence of specific receptors for bombesin/GRP was investigated on the crude membranes of implanted tumors of Hs746T cells. Saturation binding assays showed that the binding of [125I-Tyr4]bombesin to the membranes was saturable and reversible. Scatchard analysis indicated the presence of a single class of binding sites with a high affinity (Kd = 0.24 +/- 0.07 nM) and a low binding capacity (Bmax = 57.0 +/- 0.9 fmol/mg protein). In displacement studies, the binding of [125I-Tyr4]bombesin was inhibited in a dose-dependent manner by unlabelled bombesin(1-14), [Tyr4]-bombesin and GRP (14-27), but not by structurally unrelated peptides. Synthetic bombesin/GRP antagonists RC-3095, RC-3110, and RC-3950-II were all able to inhibit effectively the binding of [125I-Tyr4]bombesin to the membranes of Hs746T cells. RC-3950-II showed a higher binding affinity for bombesin receptors than RC-3095 or RC-3110. Addition of the non-hydrolyzable guanine-nucleotide analog GTP [S] to the binding buffer caused a significant reduction in the amount of [125I-Tyr4]bombesin bound to the cells, indicating that the bombesin receptor is coupled to a G-protein. In cell cultures, bombesin significantly stimulated the growth of Hs746T cells in vitro as shown by an increase in the uptake of [3H]thymidine. Bombesin antagonist RC-3095 could effectively inhibit the bombesin-stimulated growth of Hs746T cells in cultures. These observations suggest that bombesin/GRP may act as growth factors through specific receptors present on the membranes of Hs746T cells. Bombesin/GRP antagonists appear to nullify the effects of bombesin/GRP and may be useful for the treatment of gastric cancers.


Assuntos
Antineoplásicos/farmacologia , Bombesina/análogos & derivados , Bombesina/farmacologia , Fragmentos de Peptídeos/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Animais , Bombesina/antagonistas & inibidores , Bombesina/metabolismo , DNA de Neoplasias/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Humanos , Camundongos , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Transplante de Neoplasias , Células Tumorais Cultivadas
14.
AIDS Educ Prev ; 12(5 Suppl): 87-98, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11063072

RESUMO

HIV prevention research interventions usually follow protocols with specific procedures. If a community-delivered intervention uses the same procedures with the same populations as those in the original research, the behavior change effects should be similar. However, community-based providers may not replicate an intervention exactly as it was conducted in the effectiveness study. Adaptation may be needed to better meet the needs of the clients, community, or organization. We propose that interventions can be defined in terms of core elements likely to be responsible for effectiveness. These core elements cannot be changed without fundamentally changing the intervention, whereas other characteristics may be modified without altering effectiveness. HIV prevention researchers and service providers can collaborate to develop interventions that not only are effective but can also be successfully implemented by service organizations. If researchers actively involve service providers and community members in intervention planning, technology transfer goals can be better achieved.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Infecções por HIV/prevenção & controle , Serviços Preventivos de Saúde/organização & administração , Transferência de Tecnologia , Humanos , Modelos Organizacionais , Desenvolvimento de Programas , Estados Unidos
15.
IEEE Trans Biomed Eng ; 42(10): 967-72, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8582726

RESUMO

Flexible plastic waveguides (FPW) were devised for the delivery of Er-YAG laser radiation. The FPW characteristics were studied under various conditions. In vitro studies were carried out to explore the drilling procedure on extracted teeth and the FPW-tissue mutual effects. The results which were obtained proved that the FPW as a delivery device might be a substitute hand applicator for the pneumatic turbine for drilling in teeth.


Assuntos
Instrumentos Odontológicos , Terapia a Laser/instrumentação , Preparo da Cavidade Dentária/instrumentação , Desenho de Equipamento , Estudos de Avaliação como Assunto , Humanos , Técnicas In Vitro , Propriedades de Superfície , Temperatura
16.
J Endod ; 19(6): 272-6, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8228745

RESUMO

Fifteen maxillary central incisors were treated in vitro with pulsed CO2 laser radiation (wavelength:9.6-microns pulse duration:135-microseconds pulse energy:60 mJ energy density:12 J/cm2) delivered by an AgCl fiber into the root canal. Preliminary results show opening of dentin tubules as well as fused areas of hydroxyapatite in the root canal after laser treatment. Temperature measurement at the root surface showed that 40 degrees C was not exceeded. These preliminary results show the ability of this laser system to open dentin tubules and to fuse hydroxyapatite but further development in fiber technology is necessary to achieve predictable results.


Assuntos
Preparo da Cavidade Dentária/instrumentação , Cavidade Pulpar/efeitos da radiação , Dentina/efeitos da radiação , Terapia a Laser , Tratamento do Canal Radicular/instrumentação , Dióxido de Carbono , Dentina/ultraestrutura , Durapatita/efeitos da radiação , Tecnologia de Fibra Óptica , Humanos , Incisivo , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Compostos de Prata
17.
Sci Total Environ ; 277(1-3): 95-100, 2001 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-11589412

RESUMO

Non-ionic surfactants are widely used for household and industrial purposes. For different reasons the metabolites, e.g. 4-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate and 4-tert-octylphenol, are especially considered to be endocrine disruptive and thus potentially harmful for the environment. In this study, field samples of raw wastewater from different point sources, including industrial effluents, household effluents, the influent and secondary effluent of a wastewater treatment plant that treats this wastewater were monitored simultaneously. Composite samples were taken five times over periods of 1 week at nine sample sites. The results showed that the concentrations and fluxes were varying. In addition industrial, influent and effluent samples were investigated for nonylphenol (NP). The highest concentrations of bismuth active substances (BiAS) were obtained by wastewater samples from a chemical and a cloth washing company ranging from 10,200 to 65,600 microg/l and 14,600 to 33,900 microg/l BiAS, respectively. Although the concentration of BiAS in the wastewater of the paper production was only between 460 and 1200 microg/l BiAS, the NP/BiAS ratio of 0.51% was considerably higher than in other industrial effluents. The BiAS concentration in wastewater samples from households ranged from 2200 to 7900 microg/l BiAS, but the NP concentration was quite low, 0.01% of BiAS. This could be due to the effort within the EU to phase out nonylphenol polyethoxylates in household detergents. Influent concentrations between 700 and 2200 microg/l BiAS with removal rates in the WWTP ranging from 70.7 to 99.4% with an average of 92.2% could be measured.


Assuntos
Bismuto/química , Fenóis/química , Esgotos/química , Bismuto/análise , Sistema Endócrino/efeitos dos fármacos , Monitoramento Ambiental , Habitação , Indústrias , Fenóis/análise , Eliminação de Resíduos
18.
SADJ ; 57(8): 313-7, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12428525

RESUMO

UNLABELLED: The aim of the study was to make a direct comparison of the pulpal effects of laser and turbine preparations in subhuman primates. One female baboon (Papio Ursinus ursinus), weighing 15 kg, was used. General anaesthesia was administered (ketamine 100 mg/ml/kg body weight) and maintained with acepromazine (10 mg/ml/kg body weight). Class V cavities were prepared buccally in a total of 28 teeth (7 in each quadrant). Teeth in the upper right and lower left quadrants were prepared using a conventional 330 carbide bur in a high-speed fibre-optic handpiece with copious water spray. Teeth in the upper left and lower right quadrants were prepared using an Er:YAG laser drill (Fotona Twinlight, Llubljana, Slovenia) delivering 500 mJ at a pulse rate of 10 Hz and a wavelength of 2940 nm. The animal was sacrificed after 25 days. After general anaesthesia as described before, perfusion fixation of the head was accomplished with 10% neutral buffered formalin, pumped through a catheter inserted into the left carotid artery. The jaws were removed and, using a 330 carbide bur in a high speed handpiece, a continuous groove was cut through the bone and the roots at the level of the middle third of all the roots to promote thorough fixation of pulpal tissue. Decalcification and grading of the severity of the pulpal responses were conducted according to standard procedures. RESULTS: Owing to procedural errors seven teeth, FDI numbers 23, 24, 31, 34, 35, 44 and 45, had to be eliminated. The turbine-prepared teeth (N = 11) had a mean remaining dentine thickness (RDT) of 0.77 mm (SD = 0.42) and the laser-prepared teeth (N = 10) had a mean RDT of 0.81 mm (SD = 0.60). All pulps appeared normal except in one turbine-prepared tooth (12 with RDT = 0.20) and one laser-prepared tooth (27 with RDT = 0.30, where irreversible damage was caused. The only other deviations from normal were seen in the laser-treated 41 (RDT = 0.69) and the turbine-treated 36 (RDT = 0.77) where moderate hyperaemia was seen. Within the limitations of this study it can be concluded that there is no significant difference between dental pulp of teeth where Class V cavities were prepared with an Er:YAG laser drill compared with those prepared with a standard turbine drill.


Assuntos
Preparo da Cavidade Dentária/instrumentação , Polpa Dentária/lesões , Lasers/efeitos adversos , Lesões Experimentais por Radiação , Animais , Polpa Dentária/patologia , Érbio , Feminino , Temperatura Alta/efeitos adversos , Papio , Projetos Piloto
19.
Orv Hetil ; 140(29): 1611-8, 1999 Jul 18.
Artigo em Húngaro | MEDLINE | ID: mdl-10443138

RESUMO

Perinatal intensive centers deal with preterm infants of the region. Therefore, the rate of preterm deliveries at the Department of Obstetrics and Gynecology, Medical University of Pécs was high in 1997, about the double of the national rate (18.7%). Among prematures the rate of very low birth weight (VLBW) infants (less than 1500 g) was about 40%, moreover, the rate of extremely low birth weight infants (less than 1000 g) was 39% within the latter group. Related to the new regulation concerning preterm delivery the number of immature infants (weighing less than 750 g) with poor outcome increased. The most characteristic disease of preterm infants is the idiopathic respiratory distress syndrome (IRDS). This could be prevented by maternal steroid treatment, a therapy accepted worldwide, however, not so common in Hungary. Direct fetal steroid therapy may be applied also in selected cases. In the treatment of IRDS surfactant products made a breakthrough. Several factors (maternal tocolytic and fluid therapy, Cesarean section) influence the cardiopulmonary adaptation which may be monitored with impedance cardiography. Late hyponatremia and metabolic acidosis may develop in 1/3 of VLBW infants. Besides the fluid therapy the introduction of enteral feeding must be planned carefully and examination of gastric emptying with ultrasound is useful. The development of osteopenia may be prevented by passive exercise of the preterm infant. Anemia is common and human recombinant erythropoietin is available for treatment. Screening of vision, hearing, and neurodevelopmental follow up are integral parts of neonatal care. As a result of the above mentioned preventive and therapeutic interventions neonatal mortality has decreased significantly in Hungary in the past decades.


Assuntos
Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Terapia Intensiva Neonatal , Feminino , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino
20.
Orv Hetil ; 133(7): 403-5, 1992 Feb 16.
Artigo em Húngaro | MEDLINE | ID: mdl-1531869

RESUMO

Atrial natriuretic peptide (ANP) is a potent natriuretic and hypotensive substance whose importance in pregnancy has not been fully elucidated. Because abnormalities of sodium and water balance are known to be involved in the pathogenesis of toxemic pregnancy, the authors attempted to evaluate the role of ANP by measuring its plasma concentration in 16 normal and 22 toxemic pregnant women (gestational age 26-40 wks, mean 34.5 +/- 1.2 and 28-40 wks, mean 36.0 +/- 1.0, respectively). The weight gain during pregnancy was significantly higher in the toxemic group (13.9 +/- 1.0 vs 9.1 +/- 1.0 kg, p less than 0.01). Plasma ANP level in the toxemic group (40.65 +/- 6.17 pg/ml) was significantly (p less than 0.05) increased compared to that measured in the normal pregnancy group (22.46 +/- 4.22 pg/ml). There was no statistical correlation between ANP levels and gestational age or weight gain during pregnancy. The results suggest that ANP may play a role in the regulation of impaired water and sodium homeostasis in toxemic pregnancy.


Assuntos
Fator Natriurético Atrial/sangue , Pré-Eclâmpsia/sangue , Feminino , Humanos , Gravidez
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