Is chemodenervation with incobotulinumtoxinA an alternative to invasive chronic anal fissure treatments?

BACKGROUND: Botulinum toxin type A is currently strongly recommended for the treatment of anal fissures (AFs). However, there is still no consensus on dosage or injection technique. This study provides further efficacy and safety evidence in a 2-year follow-up. METHOD: Prospective, open-label, single-arm, single-center study carried out in adult patients with AFs non-responsive to previous treatments. Patients were treated with incobotulinumtoxinA (incoBoNT/A) injected in both laterals and posterior intersphincteric groove. Healing rate at 2 years was the primary endpoint. Secondary endpoints included internal anal sphincter pressures, incontinence, and safety. RESULTS: A total of 49 patients were treated with a mean incoBoNT/A dose of 40.5 U (spread across three locations). Healing rate at 2 years was 83.9% with a 24.5% of recurrence throughout the study. Only 7 patients (14.3%) reported adverse events (AEs) that were mild and temporary. Mean reduction in anal resting pressure was -9.1 mmHg at 3 months (p = 0.001). Mean reduction in voluntary squeeze pressure was -27.5 mmHg at 3 months (p < 0.001). Mean pain perception measured with a visual analog scale decreased by -6.5 points at 2 years (p < 0.001). There was an incontinence increase at 1 month of 1.3 points (p = 0.006), but baseline values were restored at 6 months. CONCLUSION: We present results that support the use of incoBoNT/A as a second line for AFs that do not respond to ointment therapy. IncoBoNT/A injection is a less invasive treatment that should be considered before surgery due to its efficacy and its safety which includes no permanent impairment. TRIAL REGISTRATION: ISRCTN90354265; Registered on 16th February 2024. Retrospectively registered.

Therapeutic yoga reduces pro-tumorigenic cytokines in cancer survivors.

INTRODUCTION: Chronic inflammation can remain many years after the completion of cancer treatment and is associated with cancer recurrence. The purpose of this study was to examine how a 16-week therapeutic yoga program (TYP) modulates the cytokine profile in heterogeneous cancer survivors. METHODS: Eligible participants were 18 years of age or older and clinically diagnosed with cancer. Consenting participants were asked to attend three, 75-min sessions weekly of TYP with meditation. Seventeen patients provided blood samples at baseline and end of study. Eight cytokines (interferon (IFN)-γ; interleukin (IL)-1b, IL-1ra, IL-4, IL-6, IL-8, IL-10; and tumor necrosis factor (TNF)-α), three receptors (sIL-6R, sTNFRI, sTNFRII), and C-reactive protein (CRP) were quantified. RESULTS: Patients were 59.6 ± 7.3 years old; over half (56%) were overweight or obese BMI ≥ 25 kg/m2); majority were female (71%) and breast cancer survivors (65%), of which 44% were Hispanic. Marked reductions were observed in all cytokines except IL-4, with significant reductions (p < 0.05) found in IL-1b (- 13%) and IL-1ra (- 13%). No significant changes were observed in soluble cytokine receptors or CRP. CONCLUSIONS: TYP led to significant reduction in circulating cytokines associated with chronic inflammation in a heterogeneous sample of cancer survivors.

HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System.

Antiretroviral therapy (ART) has transformed HIV into a chronic condition, lengthening and improving the lives of individuals living with this virus. Despite successful suppression of HIV replication, people living with HIV (PLWH) are susceptible to a growing number of comorbidities, including neuroHIV that results from infection of the central nervous system (CNS). Alterations in the dopaminergic system have long been associated with HIV infection of the CNS. Studies indicate that changes in dopamine concentrations not only alter neurotransmission, but also significantly impact the function of immune cells, contributing to neuroinflammation and neuronal dysfunction. Monocytes/macrophages, which are a major target for HIV in the CNS, are responsive to dopamine. Therefore, defining more precisely the mechanisms by which dopamine acts on these cells, and the changes in cellular function elicited by this neurotransmitter are necessary to develop therapeutic strategies to treat neuroHIV. This is especially important for vulnerable populations of PLWH with chemically altered dopamine concentrations, such as individuals with substance use disorder (SUD), or aging individuals using dopamine-altering medications. The specific neuropathologic and neurocognitive consequences of increased CNS dopamine remain unclear. This is due to the complex nature of HIV neuropathogenesis, and logistical and technical challenges that contribute to inconsistencies among cohort studies, animal models and in vitro studies, as well as lack of demographic data and access to human CNS samples and cells. This review summarizes current understanding of the impact of dopamine on HIV neuropathogenesis, and proposes new experimental approaches to examine the role of dopamine in CNS HIV infection. Graphical abstract HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System. Both substance abuse disorders and the use of dopaminergic medications for age-related diseases are associated with changes in CNS dopamine concentrations and dopaminergic neurotransmission. These changes can lead to aberrant immune function, particularly in myeloid cells, which contributes to the neuroinflammation, neuropathology and dysfunctional neurotransmission observed in dopamine-rich regions in HIV+ individuals. These changes, which are seen despite the use antiretroviral therapy (ART), in turn lead to further dysregulation of the dopamine system. Thus, in individuals with elevated dopamine, the bi-directional interaction between aberrant dopaminergic neurotransmission and HIV infection creates a feedback loop contributing to HIV associated neurocognitive dysfunction and neuroHIV. However, the distinct contributions and interactions made by HIV infection, inflammatory mediators, ART, drugs of abuse, and age-related therapeutics are poorly understood. Defining more precisely the mechanisms by which these factors influence the development of neurological disease is critical to addressing the continued presence of neuroHIV in vulnerable populations, such as HIV-infected older adults or drug abusers. Due to the complexity of this system, understanding these effects will require a combination of novel experimental modalities in the context of ART. These will include more rigorous epidemiological studies, relevant animal models, and in vitro cellular and molecular mechanistic analysis.

Daily data of Global Vertical Insolation in the four cardinal orientations in Burgos, Spain.

Daily data of Global, Diffuse and Beam Horizontal Insolation and Global Vertical (North, South, East and West orientations) insolation recorded in Burgos, Spain, are presented in this paper. Ten-minute irradiance data sets are collected over forty-five months in the experimental campaign to produce estimates of daily insolation levels. This data was derived in association with the article titled: "The PV Potential of Vertical Façades: a classic approach using experimental data from Burgos, Spain" (Díez-Mediavilla et al., in press) [1]. This dataset can be used to develop and test new solar radiation and daylight models and estimate the thermal load and lighting needs in buildings for the improvement of energy efficiency.

Formative evaluation of a proposed mHealth program for childhood illness management in a resource-limited setting in Peru.

OBJECTIVE: To conduct a formative evaluation of a proposed mobile health (mHealth) program designed to educate caregivers about management of common childhood illnesses. METHODS: A cluster-randomized sample (n = 220) of mothers in Cono Norte, Arequipa, Peru with at least one child under five completed an iPad-based survey. This descriptive study examined trends in mobile phone ownership and feasibility of and interest in mHealth across sociodemographic categories. Fisher's exact tests were used to evaluate associations. Univariate logistic regression models were fitted to calculate odds ratios and 95% confidence intervals. RESULTS: Of 220 participants, 82.3% and 95.0% reported mobile phone ownership and access, respectively. Ownership was significantly associated with educational level (P = 0.031); however, even among mothers with the lowest education, ownership approached 80%. Educational level and age, respectively, were associated with the ability to open (P < 0.001; P < 0.001), read (P < 0.001; P < 0.001), write (P < 0.001; P < 0.001), and send (P = 0.006; P = 0.047) text messages. Over 85% of mothers were interested in using their mobile phones to receive health advice for their child and to seek help during illness. Regression analyses revealed that ability to use a mobile phone was positively associated with the mother's intention to participate in the mHealth program. CONCLUSIONS: The study findings confirm widespread access to mobile phones and sufficient ability to utilize text messaging within this population of caregivers. In addition to access and feasibility, high levels of interest in using mobile phones for health-related purposes suggest the potential value associated with an mHealth program designed to improve childhood illness management in this community.

Formative evaluation of a proposed mHealth program for childhood illness management in a resource-limited setting in Peru / Evaluación formativa de un programa de salud móvil propuesto para el manejo de las enfermedades de la infancia en un entorno del Perú con recursos limitados

OBJECTIVE: To conduct a formative evaluation of a proposed mobile health (mHealth) program designed to educate caregivers about management of common childhood illnesses. METHODS: A cluster-randomized sample (n = 220) of mothers in Cono Norte, Arequipa, Peru with at least one child under five completed an iPad-based survey. This descriptive study examined trends in mobile phone ownership and feasibility of and interest in mHealth across sociodemographic categories. Fisher's exact tests were used to evaluate associations. Univariate logistic regression models were fitted to calculate odds ratios and 95% confidence intervals. RESULTS: Of 220 participants, 82.3% and 95.0% reported mobile phone ownership and access, respectively. Ownership was significantly associated with educational level (P = 0.031); however, even among mothers with the lowest education, ownership approached 80%. Educational level and age, respectively, were associated with the ability to open (P < 0.001; P < 0.001), read (P < 0.001; P < 0.001), write (P < 0.001; P < 0.001), and send (P = 0.006; P = 0.047) text messages. Over 85% of mothers were interested in using their mobile phones to receive health advice for their child and to seek help during illness. Regression analyses revealed that ability to use a mobile phone was positively associated with the mother's intention to participate in the mHealth program. CONCLUSIONS: The study findings confirm widespread access to mobile phones and sufficient ability to utilize text messaging within this population of caregivers. In addition to access and feasibility, high levels of interest in using mobile phones for health-related purposes suggest the potential value associated with an mHealth program designed to improve childhood illness management in this community.

OBJETIVO: Llevar a cabo una evaluación formativa de un programa de salud móvil (mSalud)) diseñado para educar a los cuidadores acerca del manejo de las enfermedades comunes de la infancia. MÉTODOS: Una muestra aleatorizada por conglomerados (n = 220) de madres de Cono Norte, Arequipa (Perú), que como mínimo tenían un hijo menor de cinco años, completaron una encuesta mediante iPad. Este estudio descriptivo analizó las tendencias en cuanto a la posesión de un teléfono móvil, y la viabilidad y el interés de un programa de mSalud en las diferentes categorías sociodemográficas. Se emplearon pruebas exactas de Fisher para evaluar las asociaciones. Se ajustaron modelos de regresión logística de una sola variable para calcular las razones de posibilidades y los intervalos de confianza de 95%. RESULTADOS: De las 220 participantes, un 95% tenían acceso a un teléfono móvil, de su propiedad (82,3%) o no. La posesión de un teléfono móvil se asoció significativamente con el nivel educativo (P = 0,031); sin embargo, incluso entre las madres con un nivel de formación inferior, un 80% tenían teléfono móvil. El nivel educativo y la edad, respectivamente, se asociaron con la capacidad para abrir (P < 0,001; P < 0,001), leer (P < 0,001; P < 0,001), escribir (P < 0,001; P < 0,001) y enviar (P = 0,006; P = 0,047) mensajes de texto. Más de 85% de las madres estaban interesadas en el uso de sus teléfonos móviles para recibir asesoramiento en temas de salud para su hijo y buscar ayuda en caso de enfermedad. Los análisis de regresión revelaron que la capacidad de usar el teléfono móvil se asociaba positivamente con la intención de la madre de participar en el programa de mSalud. CONCLUSIONS: Los resultados del estudio confirman la generalización del acceso a los teléfonos móviles y de la habilidad suficiente para el envío de mensajes de texto en esta población de cuidadoras. Además del acceso y la viabilidad, los elevados niveles de interés en el uso de los teléfonos móviles para las finalidades relacionadas con la salud indican el valor potencial de un programa de mSalud diseñado para mejorar el manejo de las enfermedades de la infancia en esta comunidad.

Meat-specific IgG and IgA antibodies coexist with IgE antibodies in sera from allergic patients: clinical association and modulation by exclusion diet.

IgE-mediated responses play a pivotal role in allergic patients with food intolerance. However, the association of food-specific IgG and IgA antibodies with the clinical outcome of allergic patients is still a matter of controversy. In this study we investigate whether beef-specific IgG and IgA antibodies may coexist with beef-specific IgE antibodies in food-allergic patients and examined their clinical relevance in different allergic settings. Beef-specific IgE, IgG and IgA antibodies were determined by solid-phase enzymoimmunoassay (ELISA) in a population of allergic patients (N=125) classified into patients with asthma, skin disease or gastrointestinal disorders, as well as in control subjects (N=80). IgE antibodies specific for citric fruits, tomato, cows milk, chickens egg and wheat were also determined. Beef was the predominant allergenic food in the whole population, not only for IgE (57.6 percent; P less than 0.001), but also for IgG and IgA isotypes (53.6 percent and 34.0 percent, respectively, P less than 0.001). Beef-specific IgE, IgG and IgA antibodies increased significantly in sera from patients with asthma, gastrointestinal disorders and skin allergy compared to sera from control subjects (P less than 0.001). Remarkably, IgG and IgA isotypes were significantly detected, even in the absence of IgE, in the three allergic conditions. All allergic patients, including those showing only IgG and IgA antibodies, significantly ameliorated their symptoms, and their levels of beef-specific antibodies were considerably reduced in response to a cow meat exclusion diet. While patients with gastrointestinal or skin allergic diseases were capable of tolerating beef following an established period of diet exclusion, asthmatic patients experienced a relapse of symptoms and showed a considerable increase in IgE, IgG and IgA-specific antibodies when re-challenged with a beef-enriched diet. Thus, beef-specific IgG and IgA antibodies coexist with IgE antibodies in sera from allergic patients and are significantly associated with the clinical course of allergic disorders, particularly asthma.

Towards the differentiation of non-treated and treated corundum minerals by ion-beam-induced luminescence and other complementary techniques.

Differentiation of treated and non-treated gemstones is a chief concern for major jewellery import companies. Low-quality corundum specimens coming from Asia appear to be often treated with heat, BeO or flux in order to enhance their properties as precious minerals. A set of corundum samples, rubies and sapphires from different origins, both treated and non-treated has been analysed at the Centre Européen d'Archéométrie, with ion-beam-induced luminescence (IBIL) and other complementary techniques such as Raman, proton-induced X-ray emission (PIXE), and proton-induced gamma-ray emission (PIGE). IBIL, also known as ionoluminescence, has been used before to detect impurities or defects inside synthetic materials and natural minerals; its use for the discrimination of gemstone simulants or synthetic analogues has been elsewhere discussed (Cavenago-Bignami Moneta, Gemología, Tomo I Piedras preciosas, perlas, corales, marfil. Ediciones Omega, Barcelona, 1991). PIXE has been frequently applied in the archaeometric field for material characterisation and provenance studies of minerals (Hughes, Ruby & sapphire. RWH Publishing, Fallbrook, 1997; Calvo del Castillo et al., Anal Bioanal Chem 387:869-878, 2007; Calligaro et al., NIM-B 189:320-327, 2002) and PIGE complements the elemental analysis by detecting light elements in these materials such as-and lighter than-sodium that cannot be identified with the PIXE technique (Sanchez et al., NIM-B 130:682-686, 1997; Emmett et al., Gems Gemology 39:84-135, 2003). The micro-Raman technique has also been used complementarily to ion beam analysis techniques for mineral characterisation (Novak et al., Appl Surf Sci 231-232:917-920, 2004). The aim of this study is to provide new means for systematic analysis of corundum gemstone-quality mineral, alternative to the traditional gemmologic methods; for this purpose, a Spanish jewellery import company supplied us with a number of natural corundum samples coming from different places (part of them treated as explained above). The PIXE elemental concentrations of the samples showed large quantities of calcium and lead in some cases that can be linked to treatment with fluxes or lead oxide. The plot of the chromium and iron concentration grouped the samples in various aggregates that corresponded to the different types of corundum analysed. Micro-Raman complemented the PIXE analysis corroborating the presence of lead oxides but the use of the PIGE technique was not successful for the detection of beryllium due to the low cross section of the nuclear reaction chosen for its identification. IBIL was capable of distinguishing between treated and non-treated samples of the same type based on the luminescent features of the materials.

Effect of mode of birth on purine and malondialdehyde in umbilical arterial plasma in normal term newborns.

OBJECTIVE: To examine the effect of mode of birth on plasma purine and malondialdehyde levels in normal term infants. STUDY DESIGN: Umbilical arterial cord blood was obtained immediately after birth from a convenience sample of 119 normal term newborns born by vaginal delivery, with or without oxytocin augmentation or by elective cesarean delivery. Plasma was analyzed for purine and/or malondialdehyde levels. Numeric data were analyzed utilizing independent samples t-test and ordinal data were analyzed using Mann-Whitney test. Correlation coefficients were obtained using Spearman's rho. RESULT: Uric acid levels were significantly elevated (P<0.001) in neonates undergoing vaginal birth, compared to neonates born by elective cesarean delivery. When the effect of oxytocin and length of labor was analyzed, neonates born to mothers on oxytocin had lower hypoxanthine, significantly lower xanthine (P=0.05) and higher uric acid levels. In addition, malondialdehyde levels were significantly higher (P<0.006) in neonates born to mothers who received oxytocin compared to neonates born to mothers without oxytocin augmentation. We also found significant correlations between malondialdehyde (MDA) and hypoxanthine (r=-0.465, P<0.039) and between MDA and xanthine (r=-0.753, P=0.003) in neonates born via oxytocin-augmented birth. Mode of birth had no statistically significant effect on clinical outcomes, although infants born by elective cesarean had higher incidence of acute respiratory distress and transient tachypnea of the newborn compared to those born vaginally. CONCLUSION: Neonates born by elective cesarean had the lowest purine levels in cord blood compared to neonates born vaginally. Oxytocin augmentation is associated with some degree of uterine hyperstimulation which may enhance the ATP degradation pathway resulting in the rapid conversion of hypoxanthine to xanthine and xanthine to uric acid. Significantly higher MDA levels in neonates whose mothers received oxytocin as well as significant correlation between MDA and the purines hypoxanthine and xanthine, suggest free-radical production, most likely due to xanthine oxidase activation. However, despite differences in plasma purine and malondialdehyde levels, no significant differences were seen in neonatal outcome. Further studies are required to fully characterize the effect of mode of birth on purine metabolism and free-radical production.

Some new trends in the ionoluminescence of minerals.

Ionoluminescence (IL) has mainly been used to detect impurities or defects inside synthetic materials. This paper gives a summary of new applications of IL to natural minerals that might be found in ancient pieces of jewellery or decorative artefacts (affreschi, stucchi, mosaics). Some relevant examples of its use for archaeometrical purposes are given to highlight the potential of the technique. Chemical information can be obtained by luminescent characterization of minerals. IL spectra act as digital imprint for elements or defects inside each material, enabling differentiation of natural specimens from imitations and/or synthetic analogues. Crystal field theory indicates it is the coordination number of the emitter inside the crystalline structure that gives information on its valence. Historical confusion between rubies and red spinel can easily be resolved by analysis of IL spectra. Modern synthetic diamonds can also be discriminated and blue sapphire can be distinguished from blue kyanite, a silicate that is currently being sold as its imitation. The technique can also differentiate between the synthetic and the natural gems. Polymorphs can be identified, and it is possible to recognize minerals from isomorphic series (from the same chemical group with the same structure) even when they share the same light emitter (e.g. Mn(2+), in carbonates). High-quality glasses (e.g. laser glasses) which are normally used for faking gemstones can be also detected. We fully believe IL will, in the future, be a powerful technique for determining the crystallinity of solids. This paper gives an overview of possible applications of IL to archaeometry for mineral characterization; this is a new application that still requires further study.

Shedding of PECAM-1 during HIV infection: a potential role for soluble PECAM-1 in the pathogenesis of NeuroAIDS.

Human immunodeficiency virus (HIV) infection is characterized by viral entry into the central nervous system (CNS), which is mediated, in part, by the transmigration of HIV-infected monocytes into the brain. The elaboration of chemokines and other factors by these infected cells contributes to CNS inflammation and cognitive impairment in a significant number of HIV-infected individuals. Recently, we demonstrated that HIV-infected monocyte transmigration into the CNS is enhanced greatly by the chemokine CC chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1. Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays an important role in leukocyte transmigration across the endothelium of the systemic vasculature by mediating homophilic interactions between endothelial cells (EC)-EC and EC-leukocytes, thus preserving vessel integrity. The role of PECAM-1 in HIV-infected leukocyte transmigration across the blood brain barrier (BBB) and NeuroAIDS has not been characterized. We demonstrate that in brain tissue from individuals with HIV encephalitis, there is an accumulation of cleaved, soluble forms of the extracellular region of PECAM-1 (sPECAM-1). In addition, HIV-infected individuals have elevated levels of sPECAM-1 in their sera. Our in vitro data demonstrate that HIV-infected leukocytes, when treated with CCL2, shed sPECAM-1, suggesting a mechanism of extracellular PECAM-1 cleavage and release dependent on HIV infection and CCL2. We hypothesize that sPECAM-1 production by HIV-infected leukocytes, resulting in the accumulation of sPECAM-1 within the CNS vasculature and the generation of truncated, intracellular forms of PECAM-1 within leukocytes, alters PECAM-1 interactions between EC-EC and EC-leukocytes, thus contributing to enhanced transmigration of HIV-infected leukocytes into the CNS and changes in BBB permeability during the pathogenesis of NeuroAIDS.

MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis.

Acquired immunodeficiency syndrome (AIDS)-associated dementia is often characterized by chronic inflammation, with infected macrophage infiltration of the CNS resulting in the production of human immunodeficiency virus type 1 (HIV-1) products, including tat, and neurotoxins that contribute to neuronal loss. In addition to their established role in leukocyte recruitment and activation, we identified an additional role for chemokines in the CNS. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to protect mixed cultures of human neurons and astrocytes from tat or NMDA-induced apoptosis. Neuronal and astrocytic apoptosis in these cultures was significantly inhibited by co-treatment with MCP-1 or RANTES but not IP-10. The protective effect of RANTES was blocked by antibodies to MCP-1, indicating that RANTES protection is mediated by the induction of MCP-1. The NMDA blocker, MK801, also abolished the toxic effects of both tat and NMDA. Tat or NMDA treatment of mixed cultures for 24 h resulted in increased extracellular glutamate ([Glu]e) and NMDA receptor 1 (NMDAR1) expression, potential contributors to apoptosis. Co-treatment with MCP-1 inhibited tat and NMDA-induced increases in [Glu]e and NMDAR1, and also reduced the levels and number of neurons containing intracellular tat. These data indicate that MCP-1 may play a novel role as a protective agent against the toxic effects of glutamate and tat.

Application of a thermoluminescence method for the detection of irradiated spices.

Food irradiation is extremely effective at reducing food-borne illness as well as losses caused by infestation and contamination. Despite the well-established regulations that permit irradiation to control pathogens in spices, there are no widespread methods to detect previously irradiated food. Therefore, it has become necessary to develop new detection and dose determination methods for food subjected previously to irradiation. The present work deals with the application of the thermoluminescence (TL) phenomenon to detect irradiated spices. The process is based upon the thermoluminescence properties exhibited by the polymineral content of the irradiated specimen. After separating the organic material, it is possible to extract some polymineral substances that are suitable for thermoluminescence analysis due to interaction of the spice to ionising radiation. The method was successfully applied to examine irradiated and non-irradiated paprika of Mexican origin. The spice was irradiated with gamma rays at doses of 5, 10 and 15 kGy. The separated thermoluminescent polymineral was found to be composed mainly of quartz and feldspar. The thermoluminescence glow curve of the irradiated specimen shows a wide band peaked 228, 268 and 336 degrees C, resembling closely the combined TL of quartz and feldspars. The method allows for the determination of the retrospective dose exposure.

Nutrition education training of health workers and other field staff to support chronically deprived communities.

This paper focuses on the provision of adequate training in nutrition education to health and other community development workers for their improved performance and achievement. The difficulties encountered and special care needed when dealing with low-income, chronically deprived communities are raised. A brief analysis of past and present trends in nutrition education is presented to show the progress made from restricted, authoritative and not very successful proposals to more comprehensive and participatory approaches. The need to train and update regional and field-level personnel on the new approaches, theories and models offered by nutrition education is highlighted, but the scant availability of resources for training activities may be a great limitation for this undertaking. The contribution of educational, social, psychological and communication sciences, as well as marketing, in improving and broadening the performance of health and nutrition education is recognised. Some successful nutrition education projects, implemented in different regions, using various approaches, have managed to improve the nutrition situation of low-income groups and could be used as good examples to be followed. Recommendations for implementing nutrition education projects or activities need to consider some prerequisites, such as good knowledge and analysis of the nutrition situation, careful selection of the strategies and methods, careful planning and implementation, and clear definition of the procedures and instruments for follow-up and evaluation.

Mycophenolate mofetil treatment reduces atherosclerosis in the cholesterol-fed rabbit.

Immune/inflammatory responses of arterial vessel wall constituents to lipid metabolic disturbances have been postulated to contribute to the pathogenesis of atherosclerosis. Mycophenolate mofetil (MMF), an antiproliferative agent used in clinical transplantation, has been shown to inhibit smooth muscle cell (SMC) proliferation and decrease the recruitment of monocytes into sites of chronic inflammation. This study was conducted to determine the effect of MMF on atherosclerotic plaque development after cholesterol-induced injury. New Zealand white rabbits were fed a high-cholesterol diet containing 0.5% cholesterol and 8% peanut oil. The experimental group (n = 10) was given MMF (80 mg/kg/day subcutaneously); the control group (n = 10) received placebo injections. The aortas were harvested at 12 weeks for immunohistochemical analyses. SMCs were identified by reactivity with a monoclonal antibody (mAb) to alpha smooth muscle actin. Monocytes/macrophages were detected with mAb RAM 11. Cross-sectional areas of the media and neointima were measured using computer-assisted image analysis. The density of SMCs and macrophage/foam cells within the neointima was calculated by dividing the number of cells by the area of the plaque. Total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein were significantly increased compared with levels before the initiation of a high-cholesterol diet, but there were no significant differences between the MMF-treated and untreated groups. Neointimal area in aortic tissue sections of the MMF-treated group (0.586 +/- 0.602 mm(2)) was significantly lower when compared with that in control animals (1.082 +/- 0.621 mm(2)) (P < 0.05). The densities of neointimal SMCs and monocytes/macrophages in the control group were 778 +/- 293 and 341 +/- 90 cells/mm(2), respectively. MMF treatment significantly reduced the number of neointimal SMCs (506 +/- 185 cells/mm(2)) (P < 0.05). The number of monocytes/macrophages was also reduced after MMF treatment (260 +/- 124 cells/mm(2)) but not significantly. Our results demonstrate that the administration of MMF significantly reduced neointimal SMC accumulation and plaque development in a hypercholesterolemic model of atherosclerosis.

ESR and optical absorption studies of gamma- and electron-irradiated sugar crystals

Electron spin resonance (ESR) studies of the free radicals induced in gamma- or electron-irradiated sugar crystals were performed. The number of radicals increases linearly, pointing out that this material can be used as a dosimeter. The optical absorption studies show the presence of several distinctive bands in the infrared and UV region, whose intensity changes with the irradiation dose. An interpretation of these results in terms of the formation of free radicals and possible crosslinking along the sugar molecular chains is presented.

Induction of IG9 monocyte adhesion molecule expression in smooth muscle and endothelial cells after balloon arterial injury in cholesterol-fed rabbits.

The expression of monocyte-specific adhesion molecules and chemokines by cell types within the vessel wall plays an important role in foam cell accumulation during atherosclerotic plaque development. We previously identified IG9, a novel monocyte adhesion protein that is expressed on endothelial cells (ECs) overlying human and rabbit advanced atherosclerotic plaques. The present study was designed to determine the temporal and spatial expression of IG9 and the chemokine, monocyte chemoattractant protein-1 (MCP-1), after balloon injury with (double injury) or without (single injury) prior air desiccation EC injury in the femoral arteries of rabbits fed a high-cholesterol diet. By immunohistochemical analyses, intense reactivity with monoclonal antibodies to IG9 and MCP-1 was detected 24 hours after single injury in medial smooth muscle cells (SMCs) and in SMCs of adventitial microvessels. However, monocyte infiltration of the tunica media was minimal or not detected in these sections. IG9 and MCP-1 antibody reactivity in vessel sections 28 days after single injury and 24 hours, 7 days, and 28 days after double injury was localized to medial and neointimal SMCs, foam cells, and luminal ECs overlying the plaques. Uninjured rabbit (cholesterol or normal diet) vessel sections exhibited minimal IG9 and MCP-1 immunostaining. In vitro studies using human aortic SMCs demonstrated IG9 protein induction after 24 hours of treatment with platelet-derived growth factor-BB and interferon-gamma or epidermal growth factor. IG9 expression was further increased by pretreatment of SMCs with the proatherogenic lipid, minimally oxidized low density lipoprotein. After balloon injury (24 hours), IG9 is induced in vascular SMCs before the detectable accumulation of monocytes within the vessel wall. Thus, the expression of IG9 by SMCs as well as by ECs may be an important factor in the accumulation of foam cells in atherosclerotic plaque development after arterial injury.

Human vascular smooth muscle cells possess functional CCR5.

CC chemokine receptors are important modulators of inflammation. Although CC chemokine receptors have been found predominantly on leukocytes, recent studies have suggested that vascular smooth muscle cells respond to CC chemokines. We now report that human smooth muscle cells express CCR5, a co-receptor for human immunodeficiency virus. CCR5 mRNA was detectable by RNA blot hybridization in human aortic and coronary artery smooth muscle cells. The cDNA generated by reverse transcription-polymerase chain reaction from aortic smooth muscle cells had 100% identity throughout the entire coding region with the CCR5 cloned from THP-1 cells. By immunohistochemistry, CCR5 and the CCR5 ligand, macrophage inflammatory protein-1beta (MIP-1beta), were detected in smooth muscle cells and macrophages of the atherosclerotic plaque. In smooth muscle cell culture, MIP-1beta induced a significant increase in intracellular calcium concentrations, which was blocked by an antibody to CCR5. In addition, MIP-1beta caused a calcium-dependent increase in tissue factor activity. Tissue factor is the initiator of coagulation and is thought to play a key role in arterial thrombosis. These data suggest that human arterial smooth muscle cells express functional CCR5 receptors and MIP-1beta is an agonist for these cells.

Infection of endothelial cells with Trypanosoma cruzi activates NF-kappaB and induces vascular adhesion molecule expression.

Transcriptional activation of vascular adhesion molecule expression, a major component of an inflammatory response, is regulated, in part, by the nuclear factor-kappaB/Rel (NF-kappaB) family of transcription factors. We therefore determined whether Trypanosoma cruzi infection of endothelial cells resulted in the activation of NF-kappaB and the induction or increased expression of adhesion molecules. Human umbilical vein endothelial cells (HUVEC) were infected with trypomastigotes of the Tulahuen strain of T. cruzi. Electrophoretic mobility shift assays with an NF-kappaB-specific oligonucleotide and nuclear extracts from T. cruzi-infected HUVEC (6 to 48 h postinfection) detected two major shifted complexes. Pretreatment with 50x cold NF-kappaB consensus sequence abolished both gel-shifted complexes while excess SP-1 consensus sequence had no effect. These data indicate that nuclear extracts from T. cruzi-infected HUVEC specifically bound to the NF-kappaB consensus DNA sequence. Supershift analysis revealed that the gel-shifted complexes were comprised of p65 (RelA) and p50 (NF-kappaB1). Northern blot analyses demonstrated both the induction of vascular cell adhesion molecule 1 and E-selectin and the upregulation of intercellular adhesion molecule 1 mRNA in HUVEC infected with T. cruzi. Immunocytochemical staining confirmed adhesion molecule expression in response to T. cruzi infection. These findings are consistent with the hypothesis that the activation of the NF-kappaB pathway in endothelial cells associated with T. cruzi infection may be an important factor in the inflammatory response and subsequent vascular injury and endothelial dysfunction that lead to chronic cardiomyopathy.