A role for mast cells and mast cell tryptase in driving neutrophil recruitment in LPS-induced lung inflammation via protease-activated receptor 2 in mice.

OBJECTIVE: This study aims to investigate the role of protease-activated receptor (PAR) 2 and mast cell (MC) tryptase in LPS-induced lung inflammation and neutrophil recruitment in the lungs of C57BL/6 mice. METHODS: C57BL/6 mice were pretreated with the PAR2 antagonist ENMD-1068, compound 48/80 or aprotinin prior to intranasal instillation of MC tryptase or LPS. Blood leukocytes, C-X-C motif chemokine ligand (CXCL) 1 production leukocytes recovered from bronchoalveolar lavage fluid (BALF), and histopathological analysis of the lung were evaluated 4 h later. Furthermore, we performed experiments to determine intracellular calcium signaling in RAW 264.7 cells stimulated with LPS in the presence or absence of a protease inhibitor cocktail or ENMD-1068 and evaluated PAR2 expression in the lungs of LPS-treated mice. RESULTS: Pharmacological blockade of PAR2 or inhibition of proteases reduced neutrophils recovered in BALF and LPS-induced calcium signaling. PAR2 blockade impaired LPS-induced lung inflammation, PAR2 expression in the lung and CXCL1 release in BALF, and increased circulating blood neutrophils. Intranasal instillation of MC tryptase increased the number of neutrophils recovered in BALF, and MC depletion with compound 48/80 impaired LPS-induced neutrophil migration. CONCLUSION: Our study provides, for the first time, evidence of a pivotal role for MCs and MC tryptase in neutrophil migration, lung inflammation and macrophage activation triggered by LPS, by a mechanism dependent on PAR2 activation.

Efficacy of iron-fortified rice in reducing anemia among schoolchildren in the Philippines.

BACKGROUND: Iron deficiency anemia (IDA) in the Philippines is a serious public health problem. Fortifying rice offers a great opportunity to control IDA. However, information on other types of fortificants that can be used is scarce. OBJECTIVE: To compare the effects of two types of iron fortificants in rice in improving the hematological status of schoolchildren. DESIGN: 180 randomly selected 6-to 9-year-old anemic children were randomly allocated to three groups in a double-blinded manner: One group received iron-enriched rice (IER) with extruded iron premix rice (IPR) using ferrous sulfate as fortificant (ExFeSO4); the second group received IER with extruded IPR using micronized dispersible ferric pyrophosphate (ExFeP80); and the third group received non-fortified rice (Control). These were administered daily for 5 days a week for 6 months. Blood samples were collected at baseline after 3 and 6 months. RESULTS: At baseline, one child in the ExFeP80 group was suffering from IDA; at 3 months, no IDA was found in any groups; while at 6 months, one child in the ExFeP80 developed IDA. The baseline prevalence of anemia in all groups, which was 100%, was significantly reduced to 51%, 54%, and 63% in the ExFeSO4, ExFeP80 and Control groups respectively. After 6 months, further significant reductions were observed in the ExFeSO4 (38%) and ExFeP80 (33%) but remained at 63% in the Control group. Greater, significant increases were also observed in plasma ferritin in the fortified groups than in the Control group from baseline to 6 months. The predictors of change in hemoglobin (Hb) and plasma ferritin were group allocation and basal values. CONCLUSION: The consumption of rice fortified with FeP80 using extrusion technology has similar effects as that of FeSO4 in reducing the prevalence of IDA among schoolchildren.

Estudio de prescripción-indicación de antibióticos de mayor espectro en las unidades de terapia intensiva de los hospitales de la ciudad de Buenos Aires: análisis de los patrones de utilización / Prescription-indication study of major spectrum antibiotic in intensive care units of Buenos Aires City hospitals: analysis of utilisation patterns

Los ATB de mayor espectro se utilizan más frecuentemente en Unidades de Terapia Intensiva (UTI). Objetivos: Evaluar los patrones de utilización de piperacilina/tazobactam (PIP/T), imipenem (IMP), meropenem (MRP), colistina (COL), ceftazidima (CAZ) y vancomicina (VAN) en las UTI de hospitales públicos de la Ciudad de Buenos Aires. Diseño: Estudio multicéntrico prospectivo. Métodos: Análisis de los episodios de infección en pacientes internados en UTI de ocho hospitales que recibieron estos ATB entre octubre 12 y diciembre 12 de 2005. La recolección de datos la realizó el infectólogo, y para el procesamiento se utilizó Excel. Resultados: 116 pacientes (edad X 55.6; 62.4% hombres) presentaron 143 episodios. Hubo 216 prescripciones (1.86/ pte): PIP/T 22, IMP 60, MRP 5, COL 14, CAZ 40 y VAN 75. Los diagnósticos principales fueron neumonía asociada a ARM (NptARM) 29, infección abdominal postquirúrgica (POPabd) 21, catéter (Cat) 17, neumonía sin ARM (Npt) 15, infección abdominal secundaria (Abd) 13 y sepsis sin foco (SepSF) 13. Las prescripciones según indicación más frecuentes fueron (n): PIP/T: NptARM 6, Npt 4 y Abd 3; IMP: NptARM 11, POPabd 9 y Abd 8; COL: POPabd 5 y NptARM 4; CAZ: NptARM 7 y POPabd 7; VAN: Cat 14 y NptARM 12. Período medio entre ingreso a UTI e inicio del ATB: 12 días (0-133; p = 0,0038 entre hospitales; p = 0,063 entre ATB). Duración media de tratamientos: 8 días(1-32). El 45% de las prescripciones se basaron en hallazgos bacteriológicos. Fallecieron 51 pacientes: 25/59 (42%) de tratados empíricamente y 26/77(34%) de documentados (p = 0,7). Conclusiones: El estudio de los patrones de prescripción permite establecer diferencias entre hospitales y evaluar la necesidad de intervenciones correctivas.

Food fortification: issues on quality assurance and impact evaluation in developing countries.

Quality assurance and impact evaluation are essential components of a food fortification program and should be integrated in the fortification process. Quality assurance will ensure that the micronutrient meant to be delivered is indeed reaching the target population at the correct level. Impact evaluation will determine the effectiveness of food fortification as a strategy in controlling micronutrient deficiency and enable program planners to make decisions on the future of the program. In developing countries, both quality assurance and impact evaluation are often constrained not only by inadequacy of facilities as well as financial and manpower resources, but by unclear definition of objectives and inappropriate design. It is therefore necessary to consider the target audience for the quality assurance monitoring and impact evaluation in order to clearly define their objectives and in turn suit the design to these objectives, at the same time as the limitations in financial and manpower resources are considered.

Fortification challenges and needs.

Experience in many parts of the developing world has shown that food fortification offers a cost-effective and sustainable solution to the problem of micronutrient malnutrition. Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs, governments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy. On the other hand, formidable challenges still remain in many countries in Asia, constraining the widespread adoption of this strategy. The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making. The government faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort. Industry faces the challenge of adapting its production system to the requirements of fortification in order that they can contribute to social objectives while pursuing their economic objectives. The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification, as these players in turn face the challenges that confront them.

A phase II study of gemcitabine and cisplatin combination as induction chemotherapy for untreated locally advanced cervical carcinoma.

BACKGROUND: Cisplatin-based chemoradiation for locally advanced cervical carcinoma is now the standard of care for most patients with cervical carcinoma. However, induction chemotherapy followed by surgery, particularly with newer agents or combinations remains to be explored. This study was undertaken to evaluate the antitumor activity and toxicity of gemcitabine in combination with cisplatin for untreated locally advanced cervical carcinoma. PATIENTS AND METHODS: Open-label, single center, phase II, non-randomized study of neoadjuvant gemcitabine plus cisplatin. Forty-one patients with histologic diagnosis of cervical carcinoma, with no previous treatment and staged as IB2 to IIIB, were treated with three 21-day courses of cisplatin 100 mg/m2 day I and gemcitabine 1000 mg/m2 days 1 and 8, followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated before each course and at the end of chemotherapy. RESULTS: All patients were evaluated for toxicity and 40 for response. The overall objective response rate was 95% (95% confidence interval (CI): 88%-100%) being complete in 3 patients (7.5%) and partial in 35 (87.5%). A complete pathological response was found in 6 (26%) of the 23 patients that underwent surgery. Granulocytopenia grades 3-4 occurred in 13.8% and 3.4% of the courses, respectively, whereas non-hematological toxicity was mild. CONCLUSIONS: Induction chemotherapy with the combination of gemcitabine and cisplatin is highly active for untreated cervical cancer patients and has an acceptable toxicity profile.

Nutrition research gaps addressed to medical school

This paper illustrated important gaps in nutrition research that lends themselves well for medical schools to undertake. Medical schools have the distinct opportunity to contribute to the research effort since they have clinical materials for study in the hospital or the community with which they are associated; most have adequate laboratory facilities and even access to biopsy and autopsy materials and most importantly, all have the medical expertise to back the research effort. All it takes is to awaken them to opportunities interest them in research and prod them to start. The area of basic and applied nutrition research is so vast and fertile that researchers in medical school will have no difficulty in seeking topics that suit their own professional interests and at the same time fill gaps that are of practical importance in clinical and community nutrition. What it needs is a measure of inquisitiveness, patience and a scientific frame of mind. A great deal of personal fullfilment not to mention professional advancement awaits him or her who ventures into scientific pursuit of new knowledge

Report of a seminar and workshop on Food-based Dietary Guidelines and Nutrition Education: Bridging Science and Communication.

The 3-day seminar-workshop on 'Food-based Dietary Guidelines and Nutrition Education' was held from 22-24 July 1998 in Kuala Lumpur, Malaysia to present the latest scientific information on nutrition and health and to discuss its impact on the rationale and process for the development of food-based dietary guidelines (FBDG). The first two sessions were devoted to a review of the current information on the relation between lifestyle factors and chronic diseases, particularly obesity; the present health status and food consumption patterns in Malaysia; the current consensus on carbohydrates and fats and oils and the importance of considering the glycemic index of foods; and the importance of micronutrients in health and disease. The third and fourth sessions dealt with the rationale of FBDG and the process of their development, drawing from the 1990 FAO/WHO Consultation on Development of FBDG and the experience in the Philippines and in Europe. The importance of effective dissemination of nutrition messages to the public was thoroughhly discussed. The workshop sessions arrived at recommendations on important issues in the development of FBDG in the region, including main research and information needs, the steps in the development of FBDG, and strategies for their dissemination.

Vitamin A status of Filipino preschool children given a massive oral dose.

The protection period of a 200,000 IU of vitamin A on Filipino children was determined. Subjects were 105 children aged 1-5 years given a single massive dose during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was measured by HPLC at baseline, one, two, four and six months after the administration of the dose. Results showed that baseline serum retinol levels were significantly lower than all follow-up values. Serum retinol values were maintained at levels higher than pre-supplementation values although the values decreased on the second month after supplementation. The proportions of deficient and low (< 20 microg/dl) levels were significantly lower one and six months after supplementation. All follow-up serum retinol levels of children with deficient and low values at baseline were significantly lower (p < 0.001) than those with normal values. The WHO recommendation of 200,000 IU was effective in increasing serum retinol concentrations and maintaining it above pre-supplementation levels up to 6 months after administration of the dose. It also replenished organic vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of infection also decreased among the children. Supplementation with vitamin A has likewise resulted in an increase in hemoglobin values and a decrease in the proportion of anemics (Hb < 11.0 g/dl) among the children.

Interactions among micronutrient deficiencies and undernutrition in the Philippines.

Data gathered from the 1987 National Nutrition Survey in the Philippines provided the opportunity to study the interactions among micronutrient deficiencies and undernutrition in different age groups as basis for program targeting. A randomly selected set of 50% of the households (3,200) covered by the national survey served as source of subjects. Results showed that there was a greater proportion of anemia among the undernourished (as judged by weight for age in children and weight for height in adults) (66.0%) than among the adequately nourished (54.6%) (P < 0.01). However, the observed differences in the proportion of serum vitamin A deficiency and of goiter among the undernourished compared to the adequately nourished were not significant. Also not significant were the observed higher prevalence of anemia among subjects with acceptable serum vitamin A levels for both adequately nourished and undernourished, and the higher prevalence of vitamin A deficiency among the non-anemics. Again there were no significant differences in the prevalence of anemia among goitrous and non-goitrous subjects, as well as the prevalence of goiter among anemic and non-anemic subjects. Neither were there significant differences in the prevalence of vitamin A deficiency among goitrous and non-goitrous subjects, but there were significant differences in the prevalence of goiter among vitamin A deficient and non-vitamin A deficient subjects among the 7-14 years old and among pregnant and lactating women. The study concludes that at the national level, there is apparently an interaction between anemia and protein-energy undernutrition and possibly also between goiter and vitamin A deficiency in the high-risk age groups, but between anemia on the one hand and goiter and vitamin A deficiency in the other, perhaps because of clustering in the latter conditions not found in anemia and general undernutrition. These findings may be useful in targeting communities with high prevalence of micronutrient deficiencies by using prevalence of underweight and goiter as indicators for high prevalence of anemia and vitamin A deficiency, respectively.

Interactions among micronutrient deficiencies and undernutrition in the Philippines.

Data gathered from the 1987 National Nutrition Survey in the Philippines provided the opportunity to study the interactions among micronutrient deficiencies and undernutrition in different age groups as a basis for program targeting. A randomly selected subset of 50% of the households (3,200) covered by the national survey served as source of subjects. Results showed that there was a greater proportion of anaemia among the undernourished (as judged by weight -for-age in children and weight-for-height in adults (66.0%) than among the adequately nourished (54.6%) alpha=0.01). However, the observed differences in the proportion of serum vitamin A deficiency and of goitre among the undernourished compared to the adequately nourished were not significant. Also not significant were the observed higher- prevalence of anaemia among subjects with acceptable serum vitamin A levels for both adequately nourished and undernourished, and the higher prevalence of vitamin A deficiency among the non-anaemic. Again there were no significant difference in the prevalence of anaemia among goitrous and non-goitrous subjects, as well as the prevalence of goitre among anaemic and non-anaemic subjects. Neither were there significant differences in the prevalence of vitamin A deficiency among goitrous and non goitrous subjects, but there were significant differences in the prevalence of goitre among vitamin A deficient and non-vitamin A deficient subjects among the 7-14 year olds and among pregnant and lactating women. The study concludes that at the national level there is apparently an interaction between anaemia and protein-energy undernutrition and possibly also between goitre and vitamin A deficiency in the high risk age groups, but not between anaemia on the one hand and goitre and vitamin A deficiency in another, perhaps because of clustering in the latter conditions not found in anaemia and general undernutrition. These findings may be useful in targeting communities with high prevalence of micronutrient deficiencies by using prevalence of underweight and goitre as indicators for high prevalence of anaemia and vitamin A deficiency, respectively.

Coordinated strategies for controlling micronutrient malnutrition: a technical workshop.

Participants in a November 1991 workshop concluded that coordinated strategies for controlling malnutrition due to iodine, iron, vitamin A and other micronutrients deficiencies are technically feasible and should be given consideration in planning control efforts. Coordinated surveys involving clinical, biochemical and dietary assessment of multiple micronutrients are feasible. Multiple fortification is also possible using such vehicles as salt, processed rice or sugar. Supplementation efforts can be integrated with existing health care programs. Food-based strategies are also effective. The best examples have been community-based and have included a strong nutrition and health education component designed to change food consumption patterns, improve food preservation and preparation practices, and link income-generating activities with food production activities. Successful coordinated efforts will require a strong political commitment and a supportive infrastructure. Specific recommendations include the formation of national coordinating bodies for micronutrient deficiency control, establishment of a micronutrient information network and expansion of technical exchange and training.

Nutrition and socio-economic development in Southeast Asia.

While most Third World countries, particularly in Africa and Latin America, have experienced a deterioration in child welfare as a result of the severe economic downturn in the 1980s, Southeast Asia in general managed to sustain improvements in the situation of its children because it has maintained satisfactory rates of economic growth. However, there were exceptions within Southeast Asia. The Philippines, Vietnam, Dem. Kampuchea and Laos had unsatisfactory growth rates and, consequently, unsustained nutritional gains from the 1970s through the 1980s. Economic factors exerted a big impact on the Philippine nutrition situation, particularly on the dietary status of the households and the nutritional status of children. As a result of the economic dislocation occurring in the country, the nutritional gains of 1978-82 were not maintained in succeeding years. Unlike the case of Thailand, it has been estimated that the solution to nutritional problems in the Philippines is far from being achieved in the immediate future (Villavieja et al. 1989). On the other hand, the nutrition improvements in Thailand have been as remarkable as the economic growth over the last decade. Long-term investments in health, nutrition and other social services in Thailand (as well as in Indonesia) have paid off according to the assessment by the United Nations (1990). It appears, therefore, that the nutrition situation in developing countries is highly dependent on the economic situation, globally and nationally (Cornia et al. 1987), as well as on investment in social services. Adjustment policies should, therefore, consider their implications on distribution and poverty in order that they could positively contribute to the improvement of the nutrition of the people.

PIP: An overview for Southeast Asia is provided for population growth, food availability and consumption patterns and trends in nutritional health; and example of the interaction between the economy and food consumption and nutrition in the Philippines is given. The conclusion is that Southeast Asia, to a great extent, has managed to sustain child welfare improvements through satisfactory rates of economic growth. Countries in Africa and Latin America have not been so fortunate. The exceptions in Southeast Asia are the Philippines, Vietnam, Democratic Kampuchea, and Laos; whatever economic or nutritional gains were made in the late 1970's or early 1980's were hampered due to high population growth rates and economic declines. In the Philippines, there has been political uncertainty, a very heavy debt burden (38.1, in 1989, for debt service), and a decline in Gross National Product. After 1988, economic recovery slowed and Mt. Pinatubo erupted. The result was farm land loss to volcanic ash and greater hardship conditions for the poor and nutritionally vulnerable. Food consumption surveys show increases in consumption in 1982 with a diversified diet and a significant decline in 1987 in mean daily per capita energy, protein, and nutrient intake. The prevalence of underweight preschool children declined from 21.9% in 1978 to 17.2% in 1982, and then increased to 17.7% in 1987. Regional anthropometric measurements and incidence of underweight children aged 0-6 years in 1989-90 showed improvement. Severe chronic malnutrition also improved between 1987-90, which paralleled economic improvements. The population of Southeast Asia has doubled over the past 30 years; food supply has also increased. At the national level, no country shows food shortages. Countries without enough cushion to allow for food losses or distribution problems are Democratic Kampuchea, Papua New Guinea, the Philippines, Thailand, and Vietnam, most of which also may be deficient in consumption of oils and fats. Infant mortality (IM) has declined slightly throughout the region, but particularly in Thailand, Malaysia, and Indonesia. Low-birth-weight babies were the most numerous in Laos. IM rates are similar to other countries in Africa and South Asia , with the exception of Singapore, Thailand, and Malaysia. Nutritional improvement has been the highest in Thailand and Indonesia.

Nutrition situation in metro Manila.

Summarizing the general characteristics of food consumption pattern and dietary status of the country's central urban region, the following are brought to focus: Metro Manila as compared to all urban and rural areas consumes less cereal grains but more sugars and fats and oils; consumes more of the high quality protein foods such as meat, poultry, eggs, milk and dried beans; and consumes less of fruits and vegetables. Availability and affordability of foods in the respective sectors could have affected to a large extent the magnitude of consumption differences. Although urban households had the advantage of a more varied and quantitatively higher food consumption, their nutrient intake was not really very different from rural households. Metro Manila still had a 13.7 percent calorie gap in its intake in 1987, and intake of ascorbic acid was notably lower than the rural sector. However, intake of thiamin and riboflavin as well as fat was appreciably higher in the metropolis. Briefly identifying the trends in food consumption with reference to six survey year periods from 1974 to 1987 (excluding 1984 and 1985), Metro Manila diet disclosed the following: increasing trend for sugars and syrups as well as dried beans, nuts and seeds and decreasing trend for cereal products, fruits and vegetables and condiments and others. There was a decrease in overall food consumption among Metro Manila households during the economic crisis that transpired in 1984 and 1985. However, there was a steady consumption of rice which was under price control, and a significant increase in the intake of some food items particularly green leafy and yellow vegetables which were among the cheapest food items available in Metro Manila markets. Some food adjustments were evidently resorted to during the period of economic dislocation showing the resiliency of the urban population. Metro Manila has been apparently drawing inordinately large amounts of the food supply from the rest of the country. There is therefore an "urban bias" of food supply to Metro Manila, that is, there is a much higher demand capacity for Metro Manila to draw food supply because of its higher income level and bigger population. The impact of this situation in terms of nutrition and food supply in the rural areas should be carefully examined so as not to put the rural areas in extreme disadvantage. FNRI nutrition surveys have shown that dietary energy inadequacy remains rampant in Metro Manila, while protein continues to be a marginal problem.(ABSTRACT TRUNCATED AT 400 WORDS)

Tolerance of preschoolers to two dosage strengths of vitamin A preparation.

The tolerance to two alternative large-dosage strengths of vitamin A preparation was determined in a double-blind study involving 2471 children in two municipalities in the Philippines. Each child, aged 1-6 y, not suffering from active xerophthalmia or from nausea and/or vomiting, headache, diarrhea, and fever, was randomly given 1 mL of a syrupy suspension later identified to contain 0, 60, or 30 mg vitamin A. Clinical evaluation of subjects was done by physicians 24 h and 1 wk after dosing. Nausea and/or vomiting and headache were twice as common among children given 60 mg than those given 30 mg. Severe vomiting (1.2%) was confined to those given 60 mg. Almost all experienced their symptoms within 24 h after dosing; symptoms lasted for no more than 12-24 h. The incidence of diarrhea and fever for vitamin A recipients was not significantly different from that of those receiving placebo.

A case for integrated food, nutrition and family planning programmes.

PIP: Factors in support of integration of family planning with food and nutrition porgrams include effectiveness and efficiency, family rapport, public acceptability, community response, increased interest of workers, and survival of children. Integration begins at the policy and planning level, and each concerned department needs to make its programs multidisciplinary in character at the planning level. Integration at the policy level is most important as the 1st step. Other steps are coordination at the ministerial level; joint planning and evaluation process; integration of peripheral workers and community workers; and coordination of supervisory patterns, logistical support and training. In designing a motivational message for integrated food/nutrition/family planning programs, simplicity is the key element. There are ongoing integrated food/nutrition/family planning programs in operation in the Philippines and in Indonesia.^ieng