Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. RESULTS: Serum 25(OH) vitamin D levels were lower in MS patients than in controls (p = 0.009). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (p = 0.88). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (p = 0.05). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (p = 0.65). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (p = 0.03). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 (p = 0.63). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. CONCLUSION: Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.

The -675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus, its clinical manifestations, and comorbidities in Mexican-Mestizo population.

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the -675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The -675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81-3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62-4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31-2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84-3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the -675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.

Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.

Polymorphism rs2073618 of the TNFRSF11B (OPG) Gene and Bone Mineral Density in Mexican Women with Rheumatoid Arthritis.

Osteoporosis (OP) is highly prevalent in rheumatoid arthritis (RA) and is influenced by genetic factors. Single-nucleotide polymorphism (SNP) rs2073618 in the TNFRSF11B osteoprotegerin (OPG) gene has been related to postmenopausal OP although, to date, no information has been described concerning whether this polymorphism is implied in abnormalities of bone mineral density (BMD) in RA. We evaluated, in a case-control study performed in Mexican-Mestizo women with RA, whether SNP rs2073618 in the TNFRSF11B gene is associated with a decrease in BMD. RA patients were classified as follows: (1) low BMD and (2) normal BMD. All patients were genotyped for the rs2073618 polymorphism by PCR-RFLP. The frequency of low BMD was 74.4%. Higher age was observed in RA with low BMD versus normal BMD (62 and 54 years, resp.; p < 0.001). Worse functioning and lower BMI were observed in RA with low BMD (p = 0.003 and p = 0.002, resp.). We found similar genotype frequencies in RA with low BMD versus RA with normal BMD (GG genotype 71% versus 64.4%, GC 26% versus 33%, and CC 3% versus 2.2%, resp.; p = 0.6). We concluded that in Mexican-Mestizo female patients with RA, the rs2073618 polymorphism of the TNRFS11B gene is not associated with low BMD.

Detección de trayectorias de espermatozoides humanos mediante técnicas de procesamiento de video / Detection of human sperm tracks using video processing techniques

Resumen: El análisis de motilidad espermática es muy importante para la evaluación de fertilidad humana. A menudo este análisis se lleva a cabo de forma manual, pero puede ser susceptible a errores inherentes a la naturaleza del procedimiento. Además de conllevar largos periodos de tiempo, los resultados son subjetivos y carentes de repetitividad. Con el fin de mejorar esto, presentamos un algoritmo semi-automático que rastree de manera precisa el desplazamiento de los espermatozoides. La metodología implementada se basó en la aplicación de modelos gaussianos adaptativos para detectar los espermatozoides en movimiento y segmentarlos a lo largo de los fotogramas de un video, posteriormente fueron aplicadas operaciones morfológicas y análisis de componentes conectados para reducir ruido en la imagen y calcular los centroides respectivamente. Luego, el algoritmo de Munkres y el filtro de Kalman fueron utilizados con el propósito de asignar centroides a las trayectorias. Finalmente, las trayectorias son visualizadas en pantalla. Los resultados evidencian un 90.91% de precision con respecto al análisis manual por parte de un experto. La herramienta tiene como único objetivo detectar el movimiento y trazar el desplazamiento de los espermatozoides en vídeo para muestras espermáticas humanas. Por otra parte, permite a los expertos en andrología llevar a cabo un análisis más exacto de las características individuales de los espermaozoides, teniendo así un soporte tecnológico a bajo costo, preciso y con repetitividad en los resultados que les permita emitir un diagnóstico más acertado. Por lo tanto, este método puede ayudar a especialistas a reducir periodos de tiempo y realizar un análisis más objetivo de motilidad espermática. De esta manera, el diagnóstico de fertilidad será más confiable.

Abstract: Sperm motility analysis is very important for human fertility assessment. It is often carried on manually, but this could be susceptible to mistakes due to the nature of procedure. In addition to being time-consuming, results are merely subjective and non-repeatable. In order to overcome this, we present a semi-automated algorithm that tracks accurately the sperm movements. Adaptive Gaussian models are implemented for detecting moving spermatozoa and segment them throughout video frames. Morphological operators and connected-components labeling are applied to reduce noise and calculate centroids, respectively. Then, the Munkres algorithm along with the Kalman filter are used for the purpose of assigning centroids to tracks. Finally, tracks are displayed on screen. Outcomes show a 90.91 % of accuracy regarding to manual analysis. This algorithm aims only to detect spermatozoa movement and trace its displacement in video for human sperm samples. Moreover, it allows andrology experts to perform a more exact analysis of the individual characteristics of spermatozoa, having so a low cost, accurate and repetitive technological support that will allow them to emit more precise diagnosis. Thus, this method will help specialists to reduce time periods and make more objective analysis of sperm motility. In this way, fertility diagnosis will be more reliable.

Clinical significance of the ABCB1 and ABCG2 gene expression levels in acute lymphoblastic leukemia.

OBJECTIVES: Acute lymphoblastic leukemia (ALL) is a clonal disease that accounts for 20% of acute leukemias in adults. A high percentage of adult patients (ranging from 70 to 80%) reach complete remission; however, the 5-year survival rate is only 20-40%. One of the main obstacles to treatment success is the drug resistance of leukemic cells. Therefore, our research group analyzed the ABCB1 and ABCG2 gene expression levels in 61 patients diagnosed with ALL and assessed whether the levels affected the clinical parameters and 40-month survival rate. METHODS: The ABCB1 and ABCG2 gene expression levels were analyzed using real-time polymerase chain reaction in 61 patients diagnosed with ALL and 99 healthy donors as controls. The association between ABCB1 and ABCG2 gene expression levels and clinical variables was determined using the Chi-square test and Fisher's exact test. Overall survival (OS) was determined using the Kaplan-Meier method. RESULTS: The results showed high ABCB1 and ABCG2 gene levels, which were 4.5 and 2.3 times the levels of healthy donors, respectively. A total of 52% of the study patients expressed high ABCB1 levels and were significantly associated with the high-risk patient group and a decreased 40-month survival rate of 78%. Only 49% of the patients expressed high ABCG2 gene levels. No association was found between the clinical parameters and the ABCG2 gene expression levels. CONCLUSIONS: Early detection of ABCB1 gene expression levels could be important for the diagnosis and monitoring of ALL patients.

Three-dimensional structure and molecular dynamics studies of prorrenin/renin receptor: description of the active site.

The recent finding of a specific receptor for prorrenin/renin (PRR) has brought new insights into the physiology of the renin-angiotensin-aldosterone system. No undoubtable role has been described for this receptor so far. Its role seems to be important in chronic illnesses such as hypertension, possibly participating in the cardiovascular remodeling process, and diabetes where participation in inflammation development has been described. It is not possible, however, to explore the PRR function using classical pharmacological approaches due to the lack of specific agonists or antagonists. Two synthetic peptides have been described to accomplish these roles, but no conclusive data have been provided. There are no X-ray crystallography studies available to describe the structure and potential sites for drug development. So, the aim of this work was to model and theoretically describe the PRR. We describe and characterize the whole receptor protein, its spatial conformation and the potential interactions of PRR with the synthetic peptides available, describing the amino acid residues responsible for these interactions. This information provides the basis for directed development of drugs, seeking to agonize or antagonize PRR activity and study its function in health and ill stages.

First Report of Tomato rugose yellow leaf curl virus Infecting Tomato in Argentina.

Tomato plants exhibiting typical symptoms of begomovirus infection, including leaf deformation, curling, and yellowing, were collected from cultivated fields in Lavalle Department, Corrientes, Argentina, in 2010. Although the number of affected plants was only 2% within a farm, the finding is of considerable importance since the white fly Bemisia tabaci is widely spread within the country, even in other southernmost areas such as the cinturón hortícola de Buenos Aires (horticultural belt around Buenos Aires). DNA isolated from infected tomato leaves collected from three symptomatic tomato plants was amplified by PCR with specific primers designed to amplify a region of component A and B of the Begomovirus genome (3). The amplified DNA fragment was sequenced and a new set of primers were designed based on the obtained sequences. A DNA fragment of about 1,300 bp was amplified and later the complete genome, which was 2,683 bp long. No fragments were obtained when template DNA was from non-infected leaf samples. The 2,683-bp fragment was annotated at the NCBI under Accession No. KC132844. Analysis by NCBI BLAST showed that it was highly homologous to DNA-A component of Begomovirus. Furthermore, the genome organization was typical of DNA-A component of bipartite New World begomovirus. The sequence had one open reading frame (ORF) on the viral-sense strand (AV1/CP) and four ORFs on the complementary-sense strand (AC1/Rep, AC2/TrAp, AC3/REn, and AC4). In order to confirm this finding, the viral genome was amplified by rolling circle amplification (RCA, TempliPhi 100 Amplification Kit, Amersham Biosciences) as described by the manufacturer instructions. The RCA full-length product was digested with XhoI generating a 2,700-bp DNA fragment, suggesting the presence of only one restriction site, in agreement with the bioinformatics analysis of the KC132844 sequence. This PCR product was used as template in PCR reactions with specific primers to DNA-A or DNA-B components. While the DNA-A primers generated the expected 1,300-bp fragment, those homologous to the DNA-B component did not generate amplifications. These results confirmed the identity of the DNA-A component of the isolate MT8. The full sequence of the DNA-A component was 94% homologous to the DNA-A sequence of the Uruguayan begomovirus Tomato Rugose Yellow Leaf Curl Virus-[U4.1] (JN381823.1). Therefore, considering our results and the criteria proposed by Fauquet (1), isolate MT8 is a new species of begomovirus described recently (2). This is the first report of TRYLCV in one of the main areas of tomato production in Argentina. This virus might be accompanying another begomovirus TYVSV that provoked yellow veins symptoms in tomato plants cultivated in the same area of Corrientes. These viruses appeared recently and concomitantly with the introduction of the white fly Bemisia spp. in the area, which is one of the main production areas of tomato and provides fresh tomatoes to the whole country, and in wintertime to the city of Buenos Aires, when the horticultural belt around Buenos Aires is not under production. References: (1) C. M. Fauquet et al. Arch Virol 153:783, 2008. (2) B. Márquez-Martín et al. Arch Virol 157:1137, 2012. (3) M. R. Rojas et al. Plant Dis. 77:340, 1993.

Decreased blood levels of B lymphocytes and NK cells in patients with systemic lupus erythematosus (SLE) infected with papillomavirus (HPV).

Patients with systemic lupus erythematosus (SLE) show an enhanced risk to develop human papillomavirus (HPV) infection, and aggressive forms of this condition are seen in these patients. The aim of this study was to assess the possible relationship among HPV infection, immunosuppressive therapy and levels of leukocyte subsets in patients with SLE. The following individuals were included in the study: (1) SLE patients under immunosuppressive therapy and with lesions caused by HPV (n = 16); (2) SLE patients under immunosuppressive therapy and no evidence of HPV infection (n = 20); (3) untreated SLE patients with no evidence of HPV infection (n = 7), and; (4) healthy female subjects without evidence of HPV infection (n = 10). Peripheral blood was obtained and the percentages of different lymphocyte subsets were determined by flow cytometry, with the use of the following monoclonal antibodies: CD3, CD4, CD8, CD16, CD19, CD20, CD22, CD56, and CD335 (NKp46). We found that SLE patients under immunosuppressive therapy and with lesions caused by HPV showed significantly lower levels of B lymphocytes and NK cells compared to other groups. In contrast, SLE patients receiving immunosuppressive drugs and with no evidence of HPV infection showed similar levels of B and NK cells than healthy controls. Those patients receiving mycophenolate mofetil (MMF) had a diminished number of B cells, and a positive correlation was detected between the dose of MMF and the number of HPV skin lesions. Our data suggest that therapy of SLE patients with MMF is associated with diminished levels of B and NK cells and an enhanced risk for HPV infection.

mRNA expression of MAGE-A3 gene in leukemia cells.

Leukemia-associated antigens such as proteins encoded by MAGE genes might provide tools for immunotherapy of leukemia. Positive and negative results of MAGE-A gene expression in hematological malignancies have been reported. This led us to study MAGE-A gene expression in human leukemias using RT-PCR. Among 115 leukemias from various subtypes, 14/34 (41.17%) AML were positive for one of the three genes analyzed (MAGE-A1 1/32; MAGE-A3 10/32; MAGE-B2 3/12). Expression was also detected in 23/76 (30.26%) B-cell ALL patients (MAGE-A1 2/53; MAGE-A3 20/53; MAGE-B2 1/32). One of these patients expressed both MAGE-A1 (weak signal) and -A3 (strong signal) genes. Other patient with CML were positive for MAGE-B2 (1/5, 20%). MAGE-A3 expression data were corroborated by real time RT-PCR through determination of MAGE-A3 transcript levels. We concluded that the MAGE-A3 gene is expressed at the mRNA level in a proportion of human leukemias.

[Sydenham's chorea. A clinical analysis of 55 patients with a prolonged follow-up]. / Corea de Sydenham. Análisis clinico de 55 pacientes con seguimiento prolongado.

INTRODUCTION: Sydenham's chorea is permanently on the rise in developing countries and may suddenly reappear in developed nations. PATIENTS AND METHODS: We studied a prospective series of 55 cases, involving a total of 89 outbreaks with long-term follow-ups. All the cases were considered to be rheumatic from the outset, whether they were pure choreas or accompanied by the other signs from the Jones criterion, 38 and 17 respectively, in the first outbreak. Ages ranged between 7 and 22 years, with a mean of 15, at the time of the first outbreak; there was a predominance of females (87%). RESULTS: Hemichorea accounted for 54% of cases. Presentation under treatment was mild (60%), moderate (27%) and severe (13%). Duration ranged from 30 to 365 days. Most of the patients presented just one outbreak and only 18% had multiple outbreaks, between 2 and 10 in number. Ballism was observed in five patients, a state of chorea in two of them, another two had chorea mollis and corea gravidarum was found in five of the patients. Chorea was associated to hypotonia, incoordination, fatigue, postural disorders, motor impersistence, dysarthria and altered gait. Psychiatric disorders were frequent and varied, the most predominant being anguish, irritability, psychomotor restlessness, obsessive-compulsive traits and insomnia. The only important sequela involved the heart, with 10 cases, two of which required surgery. CONCLUSIONS: Crystalline penicillin was used to eradicate streptococcus, neuroleptic agents were employed to reduce involuntary movements and psychiatric symptoms, and benzathine was utilised as a prophylaxis for relapses and sequelae.

La tomografía computada en el diagnóstico de patología de los tejidos blandos del cuello / Computed tomography in the diagnosis of pathology of soft tissues of the neck

Este artículo enfatiza la importancia de los compartimientos y espacios anatómicos del cuello en la valoración diagnóstica de patología cervical primaria y ganglionar. Nuestro propósito es enfatizar la importancia de la combinación de localizacion anatómica y de aspectos clínicos relevantes para el diagnóstico definitivo en un grupo de patologías de presentación poco frecuente.Analizamos 91 estudios de Tomografía Computada (TC) de lesiones de cuello, clasificándolos en base a sus características clínicas, localización y comportamiento tomográfico de sus lesiones en quísticas, vasculares, neurogénicas, ganglionares y tumorales.Los autores demuestran la importancia que sigue teniendo la TC en el diagnóstico cotidiano de la patología benigna y maligna encontrada a nivel del cuello.

A multinational evaluation of the efficacy, safety and acceptability of the Protectaid contraceptive sponge.

OBJECTIVE: The Protectaid sponge (Gefar Pharma, Switzerland) is a new feminine barrier contraceptive method containing three low-dose spermicidal agents. In order to evaluate its efficacy and safety profiles, an international, multicenter study has been conducted in four countries. METHODS: Healthy, presumably fertile and sexually active women were enrolled in this study and were followed at 15 days, 3, 6, 9 and 12 months. Contraceptive efficacy was assessed by a pregnancy test, while safety was evaluated by performing gynecological examinations as well as reporting adverse events. The 'acceptability' of the sponge by the women was assessed through a standard questionnaire. RESULTS: A total of 129 women were enrolled in the study, generating 1182 cycles of use of the sponge. The overall efficacy rate was 77%, with no significant influence of age or parity. Acceptability was high, with 85% of subjects being symptom- or problem-free while using the sponge. Finally, the safety profile was very good, with no clinically significant evidence of local or systemic adverse reactions. CONCLUSION: The new Protectaid sponge is a safe and effective non-hormonal contraceptive method for women.

Occupational and environmental medicine in Colombia.

Colombia is a country rich in natural resources, with a steadily developing economy. Occupational and environmental medicine (OEM) education and practice have developed relatively recently in Colombia, mainly in response to a series of long overdue (and still partially implemented) reforms to the health care, social benefits, and education systems. Expansion in general and occupational health coverage of the Colombian population and development of OEM education and training were to be achieved through a clear stimulus to private sector initiatives. Despite some measurable overall progress, the goals remain elusive. This article discusses several aspects and the perspectives for further development of the specialty in this country, in the context of the socioeconomic factors involved in that process.

Sarcoplasmic reticulum Ca2+ depletion by caffeine and changes of [Ca2+](i) during refilling in bovine airway smooth muscle cells.

BACKGROUND: In airway smooth muscle (ASM), Ca2+ influx in response to the Ca2+ depletion of the sarcoplasmic reticulum (SR) seems to play a role in the regulation of intracellular free Ca2+ concentrations ([Ca2+](i)). This study evaluates some possible Ca2+ entry pathways activated during SR-Ca2+ depletion induced by 10 mM caffeine. METHODS: Enzymatically dispersed bovine ASM cells were loaded with Fura-2/AM to permit measurement of [Ca2+](i) changes in single cells. RESULTS: Caffeine (10 mM) induced a transient increase in [[Ca2+](i) that depleted SR-Ca(2)+ content. After caffeine washout, a decrease in basal [Ca2+](i) (undershoot) was invariably observed, followed by a slow recovery. This phenomenon was inhibited by cyclopiazonic acid (5 microM). External Ca(2)+ removal in depolarized and nondepolarized cells induced a decrease in basal [Ca2+](i) that continued until depletion of the SR-Ca2+ content. The decrease in [Ca2+](i) induced by Ca2+-free physiological saline solution (PSS) was accelerated in caffeine-stimulated cells. Recovery from undershoot was not observed in Ca2+-free PSS. Depolarization with KCl and addition of D600 (30 microM) did not modify recovery. Similar results were obtained when the Na(+)/Ca2+ exchanger was blocked by substituting NaCl with KCl in normal PSS (Na(+)-free PSS) or by adding benzamil amiloride (25 microM). CONCLUSIONS: SR-Ca2+ content plays an important role in the Ca2+ leak induced by Ca2+-free medium, and does not depend on membrane potential. Additionally, recovery from undershoot after caffeine depends on extracellular Ca2+, and neither voltage-dependent Ca2+ channels nor the Na(+)/Ca2+ exchanger are involved.

Correlations between intestinal parasitosis, physical growth, and psychomotor development among infants and children from rural Nicaragua.

The correlations between malnutrition, parasitosis (especially helminth infections), and child development are complex, and studies of these interrelationships will allow health agencies to maximize screening and intervention strategies for developing countries. We examined these correlations in a cross-sectional program in Carazo State, Nicaragua. Nine hundred sixty-one children in two age strata (ages 0-24 months and ages 2-10 years) from one urban and three rural communities were screened for intestinal parasites (direct smear and ZnSO4 flotation), malnutrition, and developmental delays. Nutritional status was determined as weight-for-age (WFA), weight-for-height (WFH), and height-for-age (HFA). Developmental status (normal, suspect) was determined for the four subtests of the Denver II Screening Test. The prevalence of malnutrition was 14.6% (WFA), 8.4% (WFH), and 36.3% (HFA). Parasitosis was more prevalent in children less than 24 months of age with low HFA, whereas in older children low WFA was more closely associated with parasitic infections. Ascaris and Trichuris were more prevalent in malnourished children. On the Denver II, suspect test results in all four categories (language, social, gross motor, and fine motor) were associated with low WFA, and suspect language tests were associated with both intestinal parasites (P = 0.0003) and Ascaris infection in particular (P = 0.044). Developmental disabilities are a significant and frequently undetected health problem in developing countries, and malnutrition associated with intestinal helminth infections may be an important contributory factor for these disabilities.

PIP: Studies of the correlations between malnutrition, parasitosis, and child development will help health agencies to maximize screening and intervention strategies for developing countries. Such correlations were examined in a cross-sectional study in Carazo State, Nicaragua. 961 children aged 0-24 months and 2-10 years from 1 urban and 3 rural communities were screened for infection with intestinal parasites, malnutrition, and developmental delays. Developmental status was determined for the 4 subtests of the Denver II Screening Test. The prevalence of malnutrition was 14.6% according to weight-for-age (WFA), 8.4% for weight-for-height (WFH), and 36.3% for height-for-age (HFA). Parasitosis was more prevalent among children under age 2 years with low HFA, while low WFA was more closely associated with parasitic infections in older children. Ascaris and Trichuris were more prevalent in malnourished children. On the Denver II, suspect test results in language, social, gross motor, and fine motor were associated with low WFA, while suspect language tests were associated with both intestinal parasites, and Ascaris infection in particular. Developmental disabilities are a significant and often undetected health problem in developing countries. Malnutrition associated with intestinal helminth infections may be an important contributory factor for such disabilities.

Measuring condom use among sex workers in the Dominican Republic.

The purpose of this paper is to assess the internal consistency of self-reported condom use among sex workers in Puerto Plata and Santo Domingo, Dominican Republic. We examined the responses to questions about condom use among 4 cross-sectional samples of sex workers. We compared measures based on: (1) questions using always-to-never scales; (2) questions about use with the past 5 clients; and (3) questions about use in the past week obtained from a retrospective coital log. In each sample, more women reported 'always' using condoms with clients than with each of the past 5 clients. In 3 of the 4 samples, only about half of the women who reported 'always' using condoms used condoms with the most recent 5 clients and with all clients in the past week. Internal consistency was significantly higher when the comparison was limited to use with the most recent 5 clients and use in the past week. Self-reported measures of condom use can be difficult to interpret. Assessing the internal consistency of several measures of use provides insight into the strengths and weaknesses of each measure.

PIP: Although evaluations of interventions to curtail the spread of HIV rely, to a large extent, on self-reported changes in behavior, the validity of self-reported condom use is difficult to assess. The internal consistency of self-reported condom use was investigated among four convenience samples of commercial sex workers in Puerto Plata (n = 408) and Santo Domingo (n = 604), Dominican Republic, interviewed before and after targeted HIV/AIDS educational programs. Three measures of condom use were assessed: 1) a measure based on reported frequency of use with new clients and regular clients using an always-to-never scale, 2) a measure of use with the most recent 5 clients, and 3) a measure based on a retrospective coital log of use with clients in the past 7 days. In each sample, more women reported "always" using condoms with clients than with each of the past 5 clients. The largest discrepancy was found in the second Puerto Plata sample, where 153 women (76%) reported always using condoms with clients, but only 96 women (47.5%) reported using condoms with each of the past 5 clients. "Sometimes" users were significantly more consistent in their responses than "always" users. Internal consistency was significantly improved (83-89%) when the comparison was limited to use with the most recent 5 clients and use in the past week.

Efectos de la contaminación ambiental en la salud de los agentes de tránsito de Santafé de Bogotá, octubre de 1993 / Effects of environmental pollution in traffic polices health in Bogotá, October 1993

Objetivos- Determinar algunos efectos característicos agudos y crónicos en la salud de los agentes de tránsito, ubicados en la zona de influencia de la secretaría de tránsito y transporte de Santafé de Bogotá, expuestos a la contaminación ambiental; correlacionarlos con las mediciones ambientales de los siguientes contaminantes: Plomo (pb), Oxidos de nitrógeno (NO), Oxidos de azufre (SO), Ozono (O3), Monóxido de carbono (CO), Hidrocarburos (Hc), Partículas y Ruido; y comparar los hallazgos en la salud con un grupo no expuesto. Métodos- Se realizaron dos tipos de estudio, uno descriptivo de Prevalencía con el fin de determinar los efectos crónicos en la salud de los agentes de tránsito de Santafé de Bogotá (n=288) asociados a contaminación ambiental comparado con un grupo de personas no expuestas y otro de seguimiento prospectivo anidado en el de Prevalencía donde participaron 207 agentes, con el fín de evaluar efectos agudos y establecer una asociación con los niveles ambientales de los contaminantes evaluados durante el mes de octubre de 1993. Para el análisis estadístico se utilizaron pruebas de Prevalencía y análisis de regresión logística multivariado. Resultados- En el estudio de Prevalencía se hallaron diferencias significativas entre las prevalencias de los expuestos y no expuestos en el caso de alteraciones del sistema nervioso central siendo de 0.718 y 0.456 respectivamente y una relación positiva con el tiempo de servicio, con un RR de 1.098 = 0.042. Enfermedad pulmonar obstructiva crónica, EPOC, Asma, y alteraciones del Sistema Nervioso priférico se presentaron solo en los expuestos. El síndrome de estrés y reacción presenta una relación inversa con la edad. En el análisis multivariado se evidenció asociación con la edad en la Hipoacusia neurosensorial grado III y en los trastornos de equilibrio. De otro modo en la Hipoacusia grado II sin antecedentes ototóxicos se observó asociación con el tiempo de servicio. En el estudio de seguimiento prospectivo se hallo un incremento en las proporciones de Prevalencía entre la primera y la segunda evaluación en faringitis irritativa. Las pruebas biológicas se encontraron dentro de los limites normales. Con relación a los niveles contaminantes del estudio se encontraron superando la normal el (CO) en la estación de san Juan de Dios, NO2 en la avenida caracas con calle 53 y SO2 y partículas en la del Tunal