The impact of government- and institution-implemented COVID-19 control measures on tertiary- and regional- level intensive care units in Pietermaritzburg, KwaZulu-Natal Province, South Africa

Background. The COVID-19 pandemic has had a significant impact on healthcare systems globally as most countries were not equipped to deal with the outbreak. To avoid complete collapse of intensive care units (ICUs) and health systems as a whole, containment measures had to be instituted. In South Africa (SA), the biggest intervention was the government-regulated national lockdown instituted in March 2020. Objective. To evaluate the effects of the implemented lockdown and institutional guidelines on the admission rate and profile of non-COVID-19 patients in a regional and tertiary level ICU in Pietermaritzburg, KwaZulu-Natal Province, SA. Methods. A retrospective analysis of all non-COVID-19 admissions to Harry Gwala and Greys hospitals was performed over an 8-month period (1 December 2019 - 31 July 2020), which included 4 months prior to lockdown implementation and 4 months post lockdown. Results. There were a total of 678 non-COVID-19 admissions over the 8-month period. The majority of the admissions were at Greys Hospital (52.4%; n=355) and the rest at Harry Gwala Hospital (47.6%; n=323). A change in spectrum of patients admitted was noted, with a significant decrease in trauma and burns admissions post lockdown implementation (from 34.2 - 24.6%; p=0.006). Conversely, there was a notable increase in non-COVID-19 medical admissions after lockdown regulations were implemented (20.1 - 31.3%; p<0.001). We hypothesized that this was due to the gap left by trauma patients in an already overburdened system. Conclusions. Despite the implementation of a national lockdown and multiple institutional directives, there was no significant decrease in the total number of non-COVID-19 admissions to ICUs. There was, however, a notable change in spectrum of patients admitted, which may reflect a bias towards trauma admissions in the pre COVID-19 era

Increased expression of interleukin-6 gene in gastritis and gastric cancer

Helicobacter pylori (H. pylori) induces an intense inflammatory response, mediated by proinflammatory cytokines, including interleukin (IL)-6 and its membrane receptor (IL-6R), which activates important signaling pathways in the development of gastric disease and cancer. We investigated the gene and protein expression of IL-6 and IL-6R and the influence of polymorphisms rs1800795, rs1800796, and rs1800797 on its gene expression together with H. pylori infection. Furthermore, an in-silico analysis was performed to support our results. Gastric biopsies were obtained from patients with gastric symptoms and patients with gastric cancer (GC) and were divided into groups (Control, Gastritis, and Cancer). H. pylori was detected by PCR. Real-time-qPCR was employed to determine gene expression, and western blot assay was used to analyze protein expression levels. PCR-RFLP was used to characterize IL-6 polymorphisms. Bioinformatics analyses were performed using the Gene Expression Omnibus (GEO) database and GEO2R to screen out differentially expressed genes (DEGs). H. pylori was detected in 43.3% of the samples. Statistically significant differences were found for IL-6 (P=0.0001) and IL-6R (P=0.0005) genes among the three groups, regardless of the presence of H. pylori. Among patients with H. pylori infection, the IL-6 and IL-6R gene and protein expressions were significantly increased, highlighting IL-6 gene overexpression in patients with GC. No statistically significant differences were found for the rs1800795, rs1800796, and rs1800797 polymorphisms compared to IL-6 gene expression. The results indicated that the IL-6 polymorphisms do not influence its expression, but IL-6 and IL-6R expression seems to be altered by the presence of H. pylori.

Changes in surgical practice in 85 South African hospitals during COVID-19 hard lockdown

Background. In preparation for the COVID-19 pandemic, South Africa (SA) began a national lockdown on 27 March 2020, and many hospitals implemented measures to prepare for a potential COVID-19 surge.Objectives. To report changes in SA hospital surgical practices in response to COVID-19 preparedness.Methods. In this cross-sectional study, surgeons working in SA hospitals were recruited through surgical professional associations via an online survey. The main outcome measures were changes in hospital practice around surgical decision-making, operating theatres, surgical services and surgical trainees, and the potential long-term effect of these changes.Results. A total of 133 surgeons from 85 hospitals representing public and private hospitals nationwide responded. In 59 hospitals (69.4%), surgeons were involved in the decision to de-escalate surgical care. Access was cancelled or reduced for non-cancer elective (n=84; 99.0%), cancer (n=24; 28.1%) and emergency operations (n=46; 54.1%), and 26 hospitals (30.6%) repurposed at least one operating room as a ventilated critical care bed. Routine postoperative visits were cancelled in 33 hospitals (36.5%) and conducted by telephone or video in 15 (16.6%), 74 hospitals (87.1%) cancelled or reduced new outpatient visits, 64 (75.3%) reallocated some surgical inpatient beds to COVID-19 cases, and 29 (34.1%) deployed some surgical staff (including trainees) to other hospital services such as COVID-19 testing, medical/COVID-19 wards, the emergency department and the intensive care unit.Conclusions. Hospital surgical de-escalation in response to COVID-19 has greatly reduced access to surgical care in SA, which could result in a backlog of surgical needs and an excess of morbidity and mortality

Errores de medicación en el Servicio de Medicina de un hospital de alta complejidad / Monitoring medication errors in an internal medicine service

Background: Patients admitted to internal medicine services receive multiple drugs and thus are at risk of medication errors. Aim: To determine the frequency of medication errors (ME) among patients admitted to an internal medicine service of a high complexity hospital. Material and Methods: A prospective observational study conducted in 225 patients admitted to an internal medicine service. Each stage of drug utilization system (prescription, transcription, dispensing, preparation and administration) was directly observed by trained pharmacists not related to hospital staff during three months. ME were described and categorized according to the National Coordinating Council for Medication Error Reporting and Prevention. In each stage of medication use, the frequency of ME and their characteristics were determined. Results: A total of 454 drugs were prescribed to the studied patients. In 138 (30,4%) indications, at least one ME occurred, involving 67 (29,8%) patients. Twenty four percent of detected ME occurred during administration, mainly due to wrong time schedules. Anticoagulants were the therapeutic group with the highest occurrence of ME. Conclusions: At least one ME occurred in approximately one third of patients studied, especially during the administration stage. These errors could affect the medication safety and avoid achieving therapeutic goals. Strategies to improve the quality and safe use of medications can be implemented using this information.

Spontaneous extracranial internal carotid artery aneurysm: a case report / Aneurisma espontáneo de la arteria carótida interna extracraneal: reporte de caso

Extracranial internal carotid artery aneurysms are rare. They may result in thromboembolic phenomena but spontaneous rupture is rare. The clinical presentation may be an asymptomatic neck mass or there may be symptoms of upper aerodigestive tract compression. The diagnosis may be suspected on clinical examination but radiologic investigations play an important role in diagnosis as well as in assessing the risk of complications of surgical intervention. We present a case of a patient with an extracranial internal carotid artery aneurysm, along with a short review of the treatment options.

Los aneurismas de la arteria carótida interna extracraneal son raros. Pueden ocasionar fenómenos tromboembólicos pero la ruptura espontánea no es común. La manifestación clínica puede ser una masa asintomático en el cuello, o pueden presentarse síntomas de compresión de las vías aerodigestivas superiores. Pueden producirse indicios para el diagnóstico a partir de sospechas durante el examen clínico, pero las investigaciones radiológicas desempeñan un papel importante a la hora de diagnosticar, y evaluar el riesgo de complicaciones de la intervención quirúrgica. Presentamos un caso de un paciente con un aneurisma de la arteria carótida interna extracraneal, junto con una breve reseña de las opciones de tratamiento.

Detection of Helicobacter pylori in gastric biopsies, saliva and dental plaques of dyspeptic patients from Marília, São Paulo, Brazil: presence of vacA and cagA genes

Helicobacter pylori, a gram-negative bacterium, possesses two important virulence factors: the vacuolating toxin (vacA), and the cytotoxin-associated gene product (cagA). The aim of the present study was to evaluate the presence of H. pylori in the stomach and oral cavity of humans and compare the cagA and vacA genotypes of H. pylori found in different samples (stomach, saliva and dental plaque) from the same patient. Gastric biopsies, saliva and dental plaques were obtained from 62 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori and the alleles cagA and vacA. Persons with gastritis had a higher frequency of H. pylori -positive samples in the stomach while positive samples from gastric biopsies were significantly correlated with those from the oral cavity. There was a high H. pylori frequency in patients while the cagA gene was associated with vacA s1 alleles in gastric biopsies. Our results suggest a reservoir of the species in the oral cavity and that, in one patient, more than one H. pylori strain may exist in the saliva, dental plaque and stomach. We found a relationship between gastric infection and the bacterium in the oral cavity, with the cytotoxin genotype varying between saliva and dental plaque.(AU)

Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line

Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG-100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95 percent) of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85 percent) presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.

DNA mismatch repair gene methylation in gastric cancer in individuals from northern Brazil

Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.

Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer

Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80°C before DNA extraction. Patients had never been submitted to chemotherapy or radiotherapy, nor did they have any other diagnosed cancer. None of the gastric cancer samples presented methylated DNA sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal gastric mucosa; however, the CDKN2A promoter was methylated in 30.4 percent of gastric cancer samples, with 35 percent methylation in diffuse-type and 26.9 percent in intestinal-type cancers. CDKN2A methylation was associated with the carcinogenesis process for ~30 percent diffuse-type and intestinal-type compared to non-neoplastic samples. Thus, ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis in our samples. CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.

Actualización de los factores pronósticos del melanoma maligno / Prognostic factors for malignant melanoma: updates

Introducción: En el año 2002, el American Joint Committee of Cancer (AJCC) propuso un nuevo sistema de etapificación para el MM a partir de factores pronósticos independientes. Se ha visto que existen otros factores que no fueron analizados que podrían modificar el pronóstico. Método: Se revisaron en la literatura los factores pronósticos clínicos e histopatológicos del melanoma descritos hasta la fecha. Se consideraron los niveles de evidencia y la aplicación clínica. Resultados: Según los criterios del AJCC, para el estadio I y II, los factores pronósticos son el índice de Breslow, nivel de Clark para el grupo <1mm y la presencia de ulceración. Para el estadio III, importa el número de linfonodos comprometidos (1vs 2-3 vs >3), enfermedad micro o macrometastásica, metástasis en tránsito y satélites. Para el estadio IV, el sitio de metástasis y los valores de LDH. Se ha visto que el sexo masculino, edad avanzada y tumores localizados en extremidades son factores pronósticos adversos. A pesar que aún no se recomienda el uso rutinario del índice mitótico, se ha postulado que sería un factor pronóstico más importante que la ulceración. La presencia de regresión e invasión linfovascular serían otros factores histopatológicos de mal pronóstico. Los mecanismos moleculares de la tumorogénesis pueden mejorar la predicción del pronóstico del paciente.Conclusión: Si bien el sistema de etapificación actual provee una excelente herramienta para determinar un pronóstico general, el uso de factores pronósticos recientemente identificados permitirá realizar un pronóstico más preciso y más individualizado.

Introduction: In 2002, the American Joint Committee of Cancer (AJCC) proposed a new system for staging MM from independent prognostic factors. It appears that there are other factors that were not analyzed that could change prognosis. Method: We reviewed the literature on the clinical and pathological prognostic factors of melanoma described so far. Evidence levels and clinical application were considered.Results: According to the AJCC, the criteria for stage I and II prognostic factors are: Breslow index, Clark level for the < 1mm group, and the presence of ulceration. For stage III, the number of adenopathies involved (1vs 2-3 vs.> 3), micro or macro metastatic disease, metastases in transit and satellites are important. For stage IV, the site of metastasis and values of LDH. Adverse prognostic factors appear to be: male, elderly and having tumors in the extremities. Although the routine use of mitotic index has not been recommended yet, it has been postulated that this may be a prognostic factor more than important ulceration. The presence of regression and linfovascular invasion are other histopathological elements of poor prognosis. The molecular mechanisms of tumor formation can make prognosis more precise and individualized. Conclusion: Although the current staging system provides an excellent tool to determine an overall prognosis, the use of newly identified prognostic factors will permit a more accurate and more individualized prognosis.

TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72) polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia), and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg) = 0.69 and P (Pro) = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.

Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

Werner syndrome (WS) is a premature aging disease caused by a mutation in the WRN gene. The gene was identified in 1996 and its product acts as a DNA helicase and exonuclease. Some specific WRN polymorphic variants were associated with increased risk for cardiovascular diseases. The identification of genetic polymorphisms as risk factors for complex diseases affecting older people can improve their prevention, diagnosis and prognosis. We investigated WRN codon 1367 polymorphism in 383 residents in a district of the city of São Paulo, who were enrolled in an Elderly Brazilian Longitudinal Study. Their mean age was 79.70 ± 5.32 years, ranging from 67 to 97. This population was composed of 262 females (68.4 percent) and 121 males (31.6 percent) of European (89.2 percent), Japanese (3.3 percent), Middle Eastern (1.81 percent), and mixed and/or other origins (5.7 percent). There are no studies concerning this polymorphism in Brazilian population. These subjects were evaluated clinically every two years. The major health problems and morbidities affecting this cohort were cardiovascular diseases (21.7 percent), hypertension (83.7 percent), diabetes (63.3 percent), obesity (41.23 percent), dementia (8.0 percent), depression (20.0 percent), and neoplasia (10.8 percent). Their prevalence is similar to some urban elderly Brazilian samples. DNA was isolated from blood cells, amplified by PCR and digested with PmaCI. Allele frequencies were 0.788 for the cysteine and 0.211 for the arginine. Genotype distributions were within that expected for the Hardy-Weinberg equilibrium. Female gender was associated with hypertension and obesity. Logistic regression analysis did not detect significant association between the polymorphism and morbidity. These findings confirm those from Europeans and differ from Japanese population.

Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro

Mercury is a xenobiotic metal that is a highly deleterious environmental pollutant. The biotransformation of mercury chloride (HgCl2) into methylmercury chloride (CH3HgCl) in aquatic environments is well-known and humans are exposed by consumption of contaminated fish, shellfish and algae. The objective of the present study was to determine the changes induced in vitro by two mercury compounds (HgCl2 and CH3HgCl) in cultured human lymphocytes. Short-term human leukocyte cultures from 10 healthy donors (5 females and 5 males) were set-up by adding drops of whole blood in complete medium. Cultures were separately and simultaneously treated with low doses (0.1 to 1000 æg/l) of HgCl2 and CH3HgCl and incubated at 37°C for 48 h. Genotoxicity was assessed by chromosome aberrations and polyploid cells. Mitotic index was used as a measure of cytotoxicity. A significant increase (P < 0.05) in the relative frequency of chromosome aberrations was observed for all concentrations of CH3HgCl when compared to control, whether alone or in an evident sinergistic combination with HgCl2. The frequency of polyploid cells was also significantly increased (P < 0.05) when compared to control after exposure to all concentrations of CH3HgCl alone or in combination with HgCl2. CH3HgCl significantly decreased (P < 0.05) the mitotic index at 100 and 1000 æg/l alone, and at 1, 10, 100, and 1000 æg/l when combined with HgCl2, showing a synergistic cytotoxic effect. Our data showed that low concentrations of CH3HgCl might be cytotoxic/genotoxic. Such effects may indicate early cellular changes with possible biological consequences and should be considered in the preliminary evaluation of the risks of populations exposed in vivo to low doses of mercury.

Cytogenetic characteristics of patients with signs and symptoms of myelodysplastic syndromes in the State of Pará, Brazil

The myelodysplastic syndromes (MDS) are clonal hematopoietic diseases characterized by medullary dysplasia, cytopenias, and frequent evolution to acute myeloid leukemia. In 1982, the French-American-British (FAB) group proposed a classification for the MDS, based on morphological characteristics of peripheral blood and of the bone marrow. Later, cytogenetics proved to be a useful tool for the refinement of prognosis, through the use of the International Prognosis Score System (IPSS), as well as through evidence of clonality. Recently, the World Health Organization (WHO) proposed a new classification for the MDS, based on significant modifications of the FAB proposal, with the inclusion of chromosome analysis. A cytogenetic analysis was made of 17 patients with symptoms of MDS in the State of Para, based on WHO recommendations, and application of the IPSS. Good metaphases were obtained for 13 patients; 12 had a normal karyotype and only one had a clonal abnormality, del(3)(p25). The genes related to neoplastic processes that have been mapped to 3p are: XPC in 3p25.1 and FANCD2 and VHL in 3p25-26. Four patients had classic symptoms of MDS; in the rest the possibility of MDS was excluded or several months of observation before diagnosis were recommended. Among those with MDS, it was not possible to apply IPSS and WHO recommendations, because fundamental data were lacking, specifically the medullary blast and ring sideroblast counts. We advocate the implementation of routine cytogenetic analyses for the study of MDS, especially in patients with moderate hematopoietic dysplasia

Genotoxic effects of rotenone on cultured lymphocytes

Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.

Genomic instability in scleroderma.

Scleroderma is an enigmatic rheumatic disorder of uncertain etio-pathogenesis. Cancer has an approximately two-fold higher incidence in scleroderma patients than in the general population. There are preliminary data of acquired genetic damage in scleroderma but the significance of these observations are uncertain. To determine somatic mutation frequency at the glycophorin-A (GPA) locus in patients with limited and diffuse cutaneous scleroderma. The GPA assay measures the total somatic mutation frequency (Vf), composed of gene inactivating mutations (NO) and mutations arising from mitotic recombination (NN) in individuals heterozygous for the GPA MN blood group. Mutation frequency was determined using a validated GPA flow cytometric assay using fluorescent labeled monoclonal antibodies specific for the GPA blood groups M and N. This assay detects and enumerates progeny of red blood cell (rbc) precursor cells which have acquired genetic damage resulting in a loss of expression of one of the GPA alleles. It was found that patients with scleroderma (n = 23) had significantly elevated Vf as compared with young healthy controls (p < 0.001) and elderly controls (p = 0.03). Patients with diffuse scleroderma had higher mean Vf as compared with limited scleroderma (p = 0.055). In comparison with controls, patients with scleroderma exhibit a higher proportion of mitotic recombinant mutations than inactivating mutations (p < 0.002). There was no correlation between Vf and disease duration, age at onset or autoantibody status. We have documented evidence of acquired genetic damage at the GPA locus in scleroderma. Evidence of acquired genetic damage in this disorder may be importance in explaining both the etio-pathogenesis of scleroderma and the association of scleroderma with cancer.

Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0) originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60 percent of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.

The TGF beta receptor endoglin in systemic sclerosis.

Immunohistochemical, flow cytometric and ELISA studies were performed to examine the expression of endoglin (CD105, a TGF beta receptor) on dermal endothelial cells, peripheral blood monocytes and free and bound serum levels in patients with systemic sclerosis as compared with appropriate controls. Endoglin was found to be significantly upregulated on dermal blood vessels in patients with scleroderma (and in patients with inflammatory skin disorders) as compared to healthy skin (p < 0.05). In contrast, there was no significant difference in endoglin expression on circulating blood monocytes between scleroderma patients and patients with a rheumatic disoder or healthy control subjects; however, endoglin expression was upregulated on monocytes in inflammatory joint fluid from patients with rheumatoid arthritis. Endoglin expression on monocytes was also influenced by isolation techniques and during whole blood culture. No differences were found in circulating free or bound endoglin levels between scleroderma patients and healthy controls. In conclusion, endoglin expression on dermal endothelial cells was significantly enhanced in scleroderma but levels on circulating monocytes and in the serum were within normal limits. The functional significance of this upregulation is uncertain but may reflect endothelial activation in scleroderma.