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Resumen: Objetivo: Descripción y análisis de la relación entre las fracturas de húmero proximal y la lesión traumática del nervio axilar circunflejo. Material y método: Estudio prospectivo, observacional, de una serie de casos consecutivos de fracturas de extremo proximal de húmero. Se realizó valoración radiográfica, clasificando las fracturas según el sistema AO (Arbeitsgemeinshaft für Osteosynsthesefragen, Asociación de Grupo de Trabajo para el Estudio de la Fijación Interna de las Fracturas), y electromiografía (EMG) para la evaluación de la lesión del nervio axilar. Resultados: De 105 casos consecutivos de fracturas de húmero proximal, 31 pacientes cumplían los criterios de inclusión. Muestra: 86% mujeres y 14% hombres con edad media de 71,8 años (30-96 años). De los pacientes incluidos en el estudio, 58% presentó una EMG normal o leve axonotmesis, 23% presentó neuropatía del nervio axilar sin denervación muscular y 19%, lesión con denervación del nervio axilar. Los pacientes que sufrieron fracturas complejas de húmero proximal (AO11B y AO11C) tuvieron más riesgo de presentar lesiones tipo neuropatía axilar con denervación muscular en la EMG, siendo esta relación estadísticamente significativa (p < 0,001). Conclusiones: Los pacientes que sufren fracturas complejas de húmero proximal (AO11B y AO11C) tienen más riesgo de presentar lesiones tipo neuropatía axilar con denervación muscular en la EMG (p < 0,001). Abstract: Objective: Description and analysis of the relation between the proximal humerus fracture patterns and the traumatic injury of the axillary nerve. Material and method: Prospective, observational study of a consecutive case series that analyzed proximal humerus fractures. Radiographic evaluation was performed, and AO (Arbeitsgemeinshaft für Osteosynsthesefragen) system was used to classify the fractures. Electromyography was used to diagnose the axillary nerve injury. Results: Thirty-one patients on 105 who had a proximal humerus fracture met inclusion criteria. Eighty-six percent of the patients included were women and 14% men. The mean age was 71.8 years (30–96 years). Of the patients included in the study, 58% had normal or mild axonotmesis EMG, 23% had axillary nerve neuropathy without muscle denervation and 19% had injury with axillary nerve denervation. Patients who suffered complex fractures of the proximal humerus (AO11B and AO11C) had a higher risk of presenting axillary neuropathy type lesions with muscle denervation in the EMG, this relationship being statistically significant (p

This paper presents numerical modelling of the ballistic impact response of hybrid laminated structures, which are developed through combinations of ceramics, Ultra-High-Molecular-Weight Polyethylene (UHMWPE), Kevlar and compressed wood. It is, for the first time, to embed the compressed wood in the ballistic panel and numerically investigate the impact response of the hybrid structures made of the multiple constituent materials. Different constitutive models and the related failure criteria were employed in the modelling to capture the ballistic responses of the constituent materials and hybrid structures. The numerical simulations were compared with the corresponding experimental results with acceptable correlation. The essential features of the hybrid composite structures subjected to high velocity impact were simulated by the finite element (FE) models, such as deformation and failure modes, back-face signature and the residual velocities. The FE models developed are ready to be used to assist design lightweight composite armour with optimized ballistic resistance and self-weight.

Objective: Description and analysis of the relation between the proximal humerus fracture patterns and the traumatic injury of the axillary nerve. Material and method: Prospective, observational study of a consecutive case series that analysed proximal humerus fractures. Radiographic evaluation was performed, and AO (Arbeitsgemeinshaft für Osteosynsthesefragen) system was used to classify the fractures. Electromyography was used to diagnose the axillary nerve injury. Results: Thirty-one patients on 105 who had a proximal humerus fracture met inclusion criteria. Eighty-six percent of the patients included were women and 14% men. The mean age was 71.8 years (30–96 years). Of the patients included in the study, 58% had normal or mild axonotmesis EMG, 23% had axillary nerve neuropathy without muscle denervation and 19% had injury with axillary nerve denervation. Patients who suffered complex fractures of the proximal humerus (AO11B and AO11C) had a higher risk of presenting axillary neuropathy type lesions with muscle denervation in the EMG, this relationship being statistically significant (p

A new combination of factors enhancing the stabilization of austenite, including pre-existed austenite among quenched martensite, prior deformation, and partitioning at high temperatures is employed to create a multi-component refined microstructure in a medium Mn steel (Fe–4Mn–0.31C–2Ni–0.5Al–0.2Mo, wt.%). The microstructure evolution and phase fraction during the processing are systematically investigated using various characterization methods. The microstructure of the specimen after 0.4 strain deformation of 73% martensite–27% austenite at 250 °C and subsequent partition-annealing at 600 °C for 20 min was composed of several phases including tempered martensite, fresh martensite, pearlite, 10% of retained austenite (RA) and undissolved cementite. By increasing the annealing temperature, the pearlitic transformation was suppressed, whereas recrystallization of the deformed martensite and carbide dissolution occurred following annealing at 650 °C for 20 min resulting in an ultrafine-grained microstructure composed of equiaxed ferrite, 32% RA along with some fresh martensite during final cooling and few carbide precipitates. The results demonstrate that the combinatorial approach accelerated partitioning of alloying elements from martensite and carbides to largely pre-existing austenite is responsible for the improved austenite stabilization during intercritical annealing of the deformed dual-phase specimens. However, competitive processes are also enhanced so that the RA content is not increased by deformation.

Resumen: Introducción y objetivos: El objetivo primario fue explorar la tendencia epidemiológica de la enfermedad intestinal inflamatoria pediátrica en América Latina; los secundarios, obtener una visión general del enfoque diagnóstico/terapéutico de miembros de la SLAGHNP y explorar la relación entre la frecuencia de casos y los años del período evaluado. Material y métodos: Se realizó una encuesta en línea a pediatras gastroenterólogos de América Latina con la plataforma SurveyMonkey. Se preguntó la frecuencia anual de pacientes nuevos de 2005 a 2016, su variedad, los segmentos del tubo digestivo afectados, los métodos de diagnóstico y el tratamiento utilizado. Se evaluó la correlación entre la frecuencia anual y los años de estudio. Resultados: Se estudió a 607 pacientes; el diagnóstico de colitis ulcerativa se realizó en 475 (78.3%), de enfermedad de Crohn en 104 (17.1%) y de enfermedad intestinal inflamatoria no clasificable en 28 (4.6%). La tendencia de colitis ulcerativa tuvo un incremento lineal con coeficiente de correlación significativo entre la frecuencia de casos nuevos y el año de estudio; 67.6% tuvieron pancolitis. Los métodos de diagnóstico incluyeron datos clínicos, endoscopia y biopsias en más del 99% de los casos; los estudios de imagen se indicaron de manera selectiva. Los esquemas farmacológicos se circunscribieron a derivados del ácido 5-aminosalicílico, azatioprina, 6-mercaptopurina, infliximab y adalimumab. Conclusiones: La enfermedad intestinal inflamatoria pediátrica en América Latina parece incrementarse en el período estudiado con predominio de formas moderadas o graves de colitis ulcerativa; esta tendencia lineal puede indicar la posibilidad predictiva de incremento gradual en la próxima década, lo que es probable que tenga implicaciones epidemiológicas y clínicas. Abstract: Introduction and objectives: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. Materials and methods: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005 to 2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. Results: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn's disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. Conclusions: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications.

Introduction and aims: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. Materials and methods: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005–2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. Results: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn’s disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. Conclusions: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications. Resumen: Introducción y objetivos: El objetivo primario fue explorar la tendencia epidemiológica de la enfermedad intestinal inflamatoria pediátrica en América Latina; los secundarios, obtener una visión general del enfoque diagnóstico/terapéutico de miembros de la SLAGHNP y explorar la relación entre la frecuencia de casos y los años del período evaluado. Material y métodos: Se realizó una encuesta en línea a pediatras gastroenterólogos de América Latina con la plataforma SurveyMonkey. Se preguntó la frecuencia anual de pacientes nuevos de 2005 a 2016, su variedad, los segmentos del tubo digestivo afectados, los métodos de diagnóstico y el tratamiento utilizado. Se evaluó la correlación entre la frecuencia anual y los años de estudio. Resultados: Se estudió a 607 pacientes; el diagnóstico de colitis ulcerativa se realizó en 475 (78.3%), de enfermedad de Crohn en 104 (17.1%) y de enfermedad intestinal inflamatoria no clasificable en 28 (4.6%). La tendencia de colitis ulcerativa tuvo un incremento lineal con coeficiente de correlación significativo entre la frecuencia de casos nuevos y el año de estudio; 67.6% tuvieron pancolitis. Los métodos de diagnóstico incluyeron datos clínicos, endoscopia y biopsias en más del 99% de los casos; los estudios de imagen se indicaron de manera selectiva. Los esquemas farmacológicos se circunscribieron a derivados del ácido 5-aminosalicílico, azatioprina, 6-mercaptopurina, infliximab y adalimumab. Conclusiones: La enfermedad intestinal inflamatoria pediátrica en América Latina parece incrementarse en el período estudiado con predominio de formas moderadas o graves de colitis ulcerativa; esta tendencia lineal puede indicar la posibilidad predictiva de incremento gradual en la próxima década, lo que es probable que tenga implicaciones epidemiológicas y clínicas.

There hasn't been a previous case report of the anterior interosseous nerve injury secondary to the presence of the muscle of Gantzer in a patient with myasthenia gravis in literature before. The anterior interosseous nerve compressive syndrome, also known as Kiloh-Nevin syndrome, is a rare disorder comprising less than 1% of all upper limb neuropathies. Establishing the etiology of anterior interosseous nerve compressive syndrome is challenging because of the lack of specific clinical findings or testing. Herein is the case of a 46 years-old male presented with left eye ptosis, ophthalmoparesis, diplopia, and right-hand weakness. On physical examination, the Pinch Grip test was positive. Electromyography studies showed neurogenic atrophy in the muscles innervated by the anterior interosseous nerve, as well as a pathological decrement of the muscle action potential of more than 10% on repetitive nerve stimulation. Concluding that the presence of the Gantzer muscle caused anterior interosseous nerve compressive syndrome was mainly a diagnosis of exclusion, after careful consideration of other possible etiologies including carpal tunnel syndrome, cervical radiculopathy, and Parsonage-Turner Syndrome. Even though anterior interosseous nerve compressive syndrome is very rare, clinical suspicion ought to arise in the presence of weak radial flexor digitorum profundus and flexor pollicis longus muscles. This case highlights the importance of a thorough medical history, a meticulous physical examination, and particularly the significance of electromyography studies in diagnosing different neuropathological entities. When appropriate, these steps offer information crucial to the differential diagnosis and eventual surgical management, assisting physicians in making informed and accurate treatment decisions.

Purpose: Epidemiological surveillance of novel Coronavirus SARS CoV-2 in the Constitutional Province of Callao in Perú. Methods & Materials: We used the data collection about the notifications of cases of COVID-19. The database was uploaded from the application of the national notification system (Notiweb). We analyzed the information from 13th March in 2020 to 27th June in 2021. Concerning deaths, the names and dates also corroborated by the death notification system (Sinadef). Results: The first notified confirmed case in the region was a female patient on 13th March in 2020. We have 154 977 notifications cases as accumulated total; 97 381 confirmed cases (with laboratory analyzes that confirm infection), 43 970 suspected cases (compatible symptoms of COVID-19), 12 646 discarded cases and 984 compatible cases (suspected case more epidemiological criteria or suspected case more radiological criteria). The districts with more cases are Callao and Ventanilla. The group of age more affected was an adult (30-59 years old) with 43 702 cases (54.60%). The primary care is provided by three “Redes de Salud”, the Red de Salud Ventanilla report 17 421 confirmed cases of COVID-19, Red de Bonilla 13 706 confirmed cases and Red de Salud BEPECA 10 786 confirmed cases. The hospitals, private clinics and others notification centres report the rest of the cases. From 9290 deaths as confirmed cases, the majority occur at the big hospitals; 6948 deaths occur at Essalud Hospitals, 1175 deaths at National Hospitals, 977 deaths at the Navy Army hospital, 45 deaths at private clinics. The rest outside third-level establishments; 92 deaths on their residence place, 45 on temporary isolation services, 06 on public roads and 02 on primary care's centres. Conclusion: The province of Callao is a remarkable region in Peru because it has two points of entry to the country, the International Airport “Jorge Chavez” and the international seaport “Terminal Portuario del Callao”, and also have 01 prisons. The curve of the total number of reported cases of COVID-19 shows two waves; this second wave is currently decreasing, with 9290 deaths over 97 381 confirmed cases, we have a Lethality rate of 9.54%

A 53-year-old man presented with acute ischemic stroke, NIHSS score of 7, 28 days after traumatic subdural haematoma and 8 days after haemothorax surgery. The MRI, MRA, and cerebral angiography revealed a thrombotic occlusion of the left middle cerebral artery (MCA), M2 segment. A significant laboratory abnormality was platelet count of 784 x109/l. Endovascular treatment using Penumbra thrombectomy system and 500 mg aspirin was applied intra-arterially to enhance recanalization. Final TICI 2b/3 result was achieved and onset-to-recanalization time was 260 min. In our center, this was the first patient with acute cerebral artery occlusion treated successfully during neuro-intervention with intra-arterial application of 500 mg aspirin. On control MRI, DWI core area was not enlarged after the intervention. The patient was discharged on day 8, and on 90 days his NIHSS and mRS scores were 0. In the pathogenesis of this stroke, some non-traditional causes were discussed: post-traumatic subdural haematoma and haemothorax, surgery, as well as reactive thrombocytosis and hyperhomocysteinaemia. On 3rd month follow-up, the transcranial colour coded doppler examination detected abnormal blood flow velocities in the left MCA, M1 segment, consistent with moderate to high-grade intracranial stenosis, which was verified by cerebral CT angiography. Secondary stroke prevention of the patient was guided in accordance with clarified etiologic mechanisms and additional risk factors.

The development of successful climate services faces a number of challenges, including the identification of the target audience and their needs and requirements, and the effective communication of complex climate information, through engagement with a range of stakeholders. This paper describes how these challenges were tackled during the European Climatic Energy Mixes (ECEM) project, part of the Copernicus Climate Change Service (C3S), in order to deliver a pre-operational, proof-of-concept climate service for the European renewable energy sector. The process of iterative user engagement adopted in ECEM is described, from the initial presentation of the team’s first vision for such a service to support external stakeholders, through to evaluation of the final interactive tool for visualisation, data download and supporting documentation (the C3S ECEM Demonstrator). The outcomes of this evaluation are outlined, together with a retrospective reflection on the engagement and development process. The extent to which co-production and co-design were achieved in practice is assessed. The paper also highlights the distance travelled from the start to end of ECEM in terms of building capacity, developing a community of practice, and raising the Technology Readiness Level. The relevance of ECEM for the European climate services market is briefly considered, including the development of downstream commercial services which build upon the public C3S services. Keywords: Climate services, Sectoral information system, Renewable energy, User needs and requirements, Stakeholder engagement, Co-production

Resumen: Los trastornos funcionales de dolor abdominal tienen una alta prevalencia en los niños. Estos trastornos pueden estar presentes por sí solos o en combinación con enfermedades orgánicas, tales como la enfermedad celíaca y las enfermedades inflamatorias intestinales. La inflamación intestinal (infecciosa y no infecciosa) predispone a los niños al desarrollo de hipersensibilidad visceral que puede manifestarse como trastornos funcionales de dolor abdominal, entre ellos el síndrome de intestino irritable. La aparición de síntomas de síndrome de intestino irritable en un paciente con una enfermedad orgánica subyacente, como la enfermedad inflamatoria intestinal, es un reto clínico, dado que la misma sintomatología puede representar un periodo de exacerbación de la enfermedad inflamatoria intestinal o un trastorno de dolor abdominal funcional sobrepuesto. Así mismo, puede ser que los síntomas del síndrome de intestino irritable en un niño con diagnóstico de enfermedad celíaca ocurran por un inadecuado control de la enfermedad celíaca o por la sobreposición con un trastorno de dolor abdominal funcional. Existe poca investigación acerca de la sobreposición de los trastornos funcionales abdominales y las enfermedades orgánicas en niños. Los estudios sugieren que la sobreposición entre los trastornos funcionales de dolor abdominal y la enfermedad inflamatoria intestinal es más común en adultos que en niños. Las causas de estas diferencias de prevalencia son aún desconocidas. Solo se han publicado unos cuantos estudios que tratan el tema de la sobreposición entre la enfermedad celíaca y los trastornos funcionales abdominales en niños. El presente artículo proporciona una revisión de la literatura acerca de la sobreposición entre la enfermedad celíaca, la enfermedad inflamatoria intestinal, y los trastornos funcionales de dolor abdominal en niños, además de establecer comparaciones con estudios realizados en adultos. Abstract: Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults. Palabras clave: Dolor abdominal, Enfermedad celíaca, Enfermedad inflamatoria intestinal, Niños, Inflamación gastrointestinal, Keywords: Abdominal pain, Celiac disease, Inflammatory bowel disease, Children, Gastrointestinal inflammation

Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infusions of agalsidase alfa. For the whole cohort, the average duration of home therapy was 1 year and 11 months (range 3 months–4 years and 6 months), and during this period, compliance to treatment (number of infusions performed vs scheduled) reached 100%. The EQ-5 VAS scale was administered to patients to evaluate the self-reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up compared to baseline (home treatment start) or remaining stable. A mild increase of average disease severity, measured through Mainz Severity Score Index (MSSI), was found during hospital treatment (p

To account for progress towards conservation targets, monitoring systems should capture not only information on biodiversity but also knowledge on the dynamics of ecological processes and the related effects on human well-being. Protected areas represent complex social-ecological systems with strong human-nature interactions. They are able to provide relevant information about how global and local scale drivers (e.g., climate change, land use change) impact biodiversity and ecosystem services. Here we develop a framework that uses an ecosystem-focused approach to support managers in identifying essential variables in an integrated and scalable approach. We advocate that this approach can complement current essential variable developments, by allowing conservation managers to draw on system-level knowledge and theory of biodiversity and ecosystems to identify locally important variables that meet the local or sub-global needs for conservation data. This requires the development of system narratives and causal diagrams that pinpoints the social-ecological variables that represent the state and drivers of the different components, and their relationships. We describe a scalable framework that builds on system based narratives to describe all system components, the models used to represent them and the data needed. Considering the global distribution of protected areas, with an investment in standards, transparency, and on active data mobilisation strategies for essential variables, these have the potential to be the backbone of global biodiversity monitoring, benefiting countries, biodiversity observation networks and the global biodiversity community. Keywords: Essential variables, Global monitoring, Biodiversity, Ecosystem services, Systems approach

The induction and role of nitric oxide (NO) during antigen presentation by macrophages to T helper (Th) cell subsets was examined. When cultured with Th1 clones, macrophage APC produced NO only in the presence of cognate Ag, which in turn suppressed T cell proliferation. IFN-gamma production by the activated Th1 cells was essential for the induction of NO. Th2 cells presented with the same cognate Ag did not induce NO production and proliferated uninhibited. Coactivation of Th1 and Th2 cells specific for the same Ag indicated that Th2 cells did not inhibit NO production, but were sensitive to NO induced by stimulated Th1 cells. Antigenic activation of Th2 cells in the presence of rIFN-gamma resulted in NO-mediated inhibition of proliferation. Th2 cells provided only a cell-associated cofactor, whereas Th1 cells secreted a soluble cofactor for IFN-gamma as well, i.e., TNF-alpha. Finally, a role for IFN-gamma and NO during immune responses was studied in spleen cells obtained from immunized IFN-gamma(-/-) mice. NO production and subsequent inhibition of Ag-specific proliferation ex vivo was observed only after the addition of rIFN-gamma. These studies suggest an IFN-gamma-dependent regulatory role for NO during Ag-specific Th cell activation involving macrophages, with obvious implications for Th subset-dependent immune responses in general., (Copyright 2000 Academic Press.)

We made an effort to prepare effective cantharidinimides by heating the reactants 1 and 2a-j to 200 degrees C with toluene and triethylamine to provide 10 N-thiazolyl- and N-thiadiazolylcantharidinimides 3a-j in high yields of 48-91%. All of the synthetic compounds were tested for their capability to suppress growth of the human hepatocellular carcinoma cell lines, SK-Hep-1 and Hep 3B. The results showed that compound 3f was the most potent, and it was more cytotoxic than cantharidin. Copyright 2000 Academic Press.

To study the effect of nitric oxide (NO) on the activity of Th subsets, cloned Th1 and Th2 lymphocytes were stimulated in the presence of an NO donor. NO, when present from the start of incubation, inhibited the proliferation of both Th subsets dose-dependently, achieving complete inhibition at a relatively low level. The addition of NO 24 h after the onset of T cell stimulation also resulted in reduced proliferation of both Th subsets, suggesting that NO affects a late process during T cell activation. Stimulation of T cells in the presence of NO did not induce apoptosis at the concentrations that completely inhibited proliferation, although apoptosis became evident at higher NO concentrations. The secretion of several cytokines (i.e., IFN-gamma, IL-4, and IL-5) was slightly upregulated, while IL-2 production was modestly inhibited in the presence of NO. However, exogenous IL-2 did not reverse the NO-induced inhibition of T cell proliferation, nor did additional stimulation with phorbol esters. Finally, expression of IL-2R was modestly decreased in the presence of NO, although TCR expression was not affected. These studies demonstrate that relatively low concentrations of NO induce a strong and specific inhibition of T cell proliferation in both Th subsets, suggesting that local NO production may regulate Th-mediated tissue inflammation., (Copyright 1999 Academic Press.)