Small interfering RNA for cancer treatment: overcoming hurdles in delivery.

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

Expression of an immunogenic LTB-based chimeric protein targeting Zaire ebolavirus epitopes from GP1 in plant cells.

KEY MESSAGE: An antigenic protein targeting two epitopes from the Zaire ebolavirus GP1 protein was expressed in plant cells rendering an antigen capable of inducing humoral responses in mouse when administered subcutaneously or orally. The 2014 Ebola outbreak made clear that new treatments and prophylactic strategies to fight this disease are needed. Since vaccination is an intervention that could achieve the control of this epidemic disease, exploring the production of new low-cost vaccines is a key path to consider; especially in developing countries. In this context, plants are attractive organisms for the synthesis and delivery of subunit vaccines. This study aimed at producing a chimeric protein named LTB-EBOV, based on the B subunit of the Escherichia coli heat-labile enterotoxin as an immunogenic carrier and two epitopes from the Zaire ebolavirus GP1 protein recognized by neutralizing antibodies. The LTB-EBOV protein was expressed in plant tissues at levels up to 14.7 µg/g fresh leaf tissue and proven to be immunogenic in BALB/c mice when administered by either subcutaneous or oral routes. Importantly, IgA and IgG responses were induced following the oral immunization. The potential use of the plant-made LTB-EBOV protein against EBOV is discussed.

Situación del brote de Ébola en África Occidental en el año 2014 / Status Ebola outbreak in West Africa in 2014

Resumen Desde el comienzo del brote en diciembre del 2013, y hasta el corte del 20 de septiembre de 2014, de un total de 6,185 casos probables de Ébola, se han registrado un total de 2,909 defunciones. Con una letalidad inferior al 50%, considerablemente menor a la reportada en brotes previos de la enfermedad, se cree que dichas estimaciones están sesgadas debido a la dificultad en la recolección y análisis de la información. El 23 de septiembre, la OMS presentó una revisión a dichas estimaciones, señalando una letalidad del 70%. El brote se registró originalmente en Liberia y Guinea, y posteriormente se han repostado casos en Nigeria, Sierra Leona y Senegal. Todos los casos confirmados por laboratorio han sido positivos al vírus del Ébola. La fuente inicial del brote se localizó en la aldea de Meliandou, prefectura de Guáckádou, Guinea. El caso índice fue un niño de 2 años, el cual falleció el 6 de diciembre de 2013. Su madre, hermana y abuela también fallecieron también por la enfermedad. La gente de la aldea infectada por estas víctimas iniciales transmitió el brote a aldeas aledañas. El brote se esparció inicialmente a Liberia y posteriormente a Sierra Leona. En los tres países continúa la circulación del virus. La llegada de algunos casos a Nigeria y Senegal obligó a dichos países a cerrar sus fronteras, y a poner en cuarentena a ciudadanos de los que se sospechara que estuvieran infectados. Hasta la fecha, ambos países no han presentado casos nuevos, por lo que se consideran en control. Asimismo, se han reportado casos importados de dichos países en Estados Unidos, Francia, Alemania, España, Suiza y el Reino Unido.

Abstract Since the onset of the outbreak im December 2013 and up to the September 20 cut-off, there have been 2,909 deaths in the 6,185 likely cases of Ebola. It is considered that the letality under 50%, considerably lower tan the one reported in previous outbreaks of the disease, is biased due to the dificulty to collect and analyze information. On September 23, WHO showed a review of such estimations, indicating 70% letality. The outbreak was originally reported in Liberia and Guinea. Further cases were reported in Nigeria, Sierra Leone, and Senegal. All the cases confirmed by laboratory have been EBOV positive. The initial source of the outbreak was found in the village called Meliandou in the in Guéckédou Prefecture, Guinea. The index case was a two-year-old boy, who die don December 6, 2013. His mother, sister and grandmother also died because of the disease. The people from this village transmitted the disease to people in nera-by villages. The outbreak initially spread to Liberia and then to Sierra Leone. Virus circulation continues in three countries. The transmision of some cases to Nigeria and Senegal led these countries to close their borders to the three formerly mentioned countries and quarantine suspicious individuals. So far, neither country has presented new cases; hence they are considered under control. Likewise, cases imported from those countries into the United States, France, Germany, spain, Switzerland, and the Uited Kingdom have been reported.

Tropical forests: present status and future outlook.

Tropical forests still cover almost 8 million km squared of the humid tropics but they are being destroyed at ever-more rapid rates. In 1989, the area deforested amounted to 142,200 km squared, or nearly 90% more than in 1979. Thus, whereas the 1989 amounted total to 1.8% of the remaining biome, the proportion could well continue to rise for the foreseeable future, until there is little forest in just a few decades. Deforestati on patterns are far from even throughout the biome. In much of the Southeast and Southern Asia, East and West Africa, and Central America, there is likely to be little forest left by the year 2000 or shortly thereafter. But in the Zaire basin, western Brazilian Amazonia, and the Guyana highlands, sizeable expanses of forest could persist a good while longer. The main agent of deforestation in the 'shifted cultivator' or displaced peasant, who, responding to land hunger and general lack of rural development in traditional farming areas of countries concerned, feels there is no alternative but to adopt a slash-and-burn lifestyle in forestlands. This person is now accounting for at least 60% of deforestation, a rapidly expanding proportion. However, he receives far less policy attention than the commercial logger, the cattle rancher, and other agents of deforestation.

[Primary care of low birth weight premature infants in the rural areas of Africa]. / Cuidados basicos de los prematuros de bajo peso en las areas rurales de Africa.

PIP: The Evangelical Medical Center in Nyankunde, Zaire, has had some success in treating low birth weight premature infants despite its lack of mechanical respiratory assistance and permanent parenteral feeding. But the norms and procedures for attending to newborns have varied in recent years due to frequent changes in the hospital's administration. A retrospective study was conducted of the 46 infants weighing 1800g or less who were born at the hospital between January 1985-February 1988 to determine the correlation between feeding, antibiotic therapy, and temperature control and survival of the infants. Feeding was considered accomplished if the infant accepted at least 90 ml/kg of maternal milk through a nasogastric tube on the 1st day with a progressive increase in liquids in the 3 following days. Antibiotic therapy was considered given when gentamycin, penicillin, or ampicillin was administered. The temperature was considered controlled if it was taken at least 4 times daily during the 1st 3 days. 7 of the 46 infants were excluded from the study, 3 because their birth weight was less than 1000 g and 4 for inadequate information. The 3 remaining infants had an average birth weight of 1510 g. Gestational ages at birth ranged from 30-35 weeks. 19 were male and 20 female. 27 (69%) survived and were discharged from the hospital. 8 boys and 4 girls died. The wright of those who died ranged from 1140-1760 g. 21 of the 26 who were fed survived, vs. only 6 of the 13 who were not fed. Almost all the mothers were capable of adequately breast feeding. 19 of the 24 patients receiving antibiotics survived, vs. 8 of the 15 who did not. 25 of the 34 whose temperature was routinely taken survived, vs. 2 of 5 for whom it was not. 17 of the 21 infants receiving all 3 forms of treatment survived (81%), vs. 10 of 18 who received none (56%). More detailed prospective studies are needed to confirm the effectiveness of these simple measures and to evaluate other measures appropriate for rural and poorly equipped maternity centers in developing countries.^ieng

Cesarean section.

PIP: The leading cause of maternal mortality and morbidity in developing countries is the lack of cesarean section deliveries due to the tremendous logistical, cost, and training problems associated with this procedure. This article describes the need for raising cesarean section rates in developing countries and what can be done with existing inadequate health care in these countries to increase these rates. 5 to 10% of all births should be done by cesarean section, yet only 0.3% of births in rural Zaire are cesarean sections. To help educate health officials about women who may need a cesarean section, this article provides: 5 basic warning signs of pregnancy complications, characteristics of high risk women, and women in their 3rd trimester who need to be referred. Crucial factors that delay mothers from getting prenatal care include cultural obstacles and undereducated traditional birth attendants. Complication signs include severe vomiting, swelling of face, feet and hands, vaginal bleeding, headache and fever. High risk mothers are age 18 or 35 years, have had 5 or more previous births, and under 150 cm. in height, experienced an abortion or stillbirth with previous pregnancy or delivered by cesarean section, had previous cephalo-pelvic disproportion or in labor 12 hours, or has chronic medical problems. Third trimester women experiencing or developing hypertensive diseases, non-vertex presentation, severe anemia, multiple birth or antepartum bleeding should be referred to a health center where a cesarean can be done if necessary.^ieng

[Problems posed by HIV infection in women in tropical zones]. / Les problèmes posés par l'infection à virus HIV chez les femmes en zone tropicale.

Retroviruses (mainly H.I.V. 1 and H.I.V. 2) are now largely spread over in Central Africa and Caribbean Islands, particularly in large cities. Their transmission is essentially horizontal and mainly sexual. As a matter of fact, sexual transmission is responsible in about 80% of the cases, leaving only a small percentage to transmission by needle (or by any aggressive material), blood or blood by-products. As far as sexual transmission is concerned, it is essentially heterosexual, in spite of the primary epidemic outbreak in the occidental world that focused interest toward male homosexual group, the first exposed to A.I.D.S. Nowadays we know that heterosexual transmission is important and bi-directionnal, even if transmission female to male has seemed to be more difficult to enlight, as it is common in sexually transmitted diseases. Transmission risk to an heterosexual partner is between 20 and 70%. Virus is present in semen, and in cervico-vaginalis secretions during all menstruation cycle. Vertical transmission, mother to child, through placenta or during delivery is frequent, and is of about 50%. First data on heterosexual transmission have been found in Central Africa, indicating high rates for prostitutes, their "customers", unmarried women with numerous partners, women with an other S.T.D. A.I.D.S. in child has been first described in Haïti and in Zaïre. The very important role played by heterosexual transmission imposed sanitary education and usage of contraceptives which are efficient but difficult to firmly recommended for social and cultural considerations.

PIP: The retrovirus responsible for AIDS began circulating in Africa during the 1970s. Seroepidemiologic studies in Zaire and elsewhere in Central Africa show infection rates of 6-10%, with urban rates even higher and most rural rates close to zero. The modes of transmission are analogous to those of hepatitis B. Homosexual transmission has probably played a small role in Africa. Most epidemiological studies in Central Africa show that almost all seropositive persons are young sexually active adults, with the most affected age groups 20-30 for women and 30-40 for men. The risk of male to female sexual transmission appears to be about 20%, but increases with prolonged relationships. Sperm is able to induce a chronic immunological stimulation and immune perturbations favoring clinical expression of the infection, especially if the sperm comes in contact with the partner's blood because of erosion of the vaginal or anal mucus. Infection of men by women is harder to demonstrate but it cannot yet be confirmed that there are significant differences related to sex. The virus is present in cervicovaginal secretions during the entire menstrual cycle. Seroprevalence rates among prostitutes in Central Africa have increased steadily and are correlated to the time spent as a prostitute and the annual number of clients. Sexually transmitted diseases that disturb the genital mucus appear to favor infection during heterosexual intercourse. In Zaire, 61% of women and 36% of men with AIDS are unmarried. For both sexes, numerous partners appear to increase the risk of infection. Frequent use of prostitutes increases the risk for men. Transmission from mothers to infants can occur during delivery or transplacentally during any trimester of pregnancy. The risk of transmission from an infected mother appears to be about 50%. HIV infection does not appear to have any specific clinical manifestation in the female genital tract. Some studies suggest that the likelihood of 1st trimester spontaneous abortion or of postnatal mortality is increased in infants of seropositive mothers. The clinical characteristics of AIDS in children are not specific and a positive serological test in necessary to confirm the diagnosis. Prevention of HIV infection in the foreseeable future will require health education and the use of condoms, which gained little acceptance in most of Africa.

Third world family planning programs: measuring the costs.

PIP: The use of cost-benefit analysis (CBA) and cost-effectiveness analysis (CEA) is explained and demonstrated in evaluating Third World family planning programs. CBA, which aids decisions on alternate uses of investment funds, e.g., family planning versus new schools, helped convince Third World governments to adopt family planning programs because of their economic value in overall development. CEA is a technique which can show which family planning delivery systems work best for the money expended as measured, e.g., by cost per acceptor, per "couple-year of protection" against the risk of pregnancy, or per birth averted. This is increasingly necessary in the 1980s as funds for family planning are being pinched in both developing and donor countries. At the same time it is estimated that annual expenditures on family planning in the Third World must rise from the current $1 billion to $64 billion by the year 2000 if this population is to be eventually stabilized. Following a general description of the 2 techniques, 9 case studies from Brazil, Colombia, Ghana, Haiti, India, Thailand, and Zaire are presented to demonstrate what cost-effectiveness analysis has revealed about such issues as integration of family planning with health services, use of paramedical staff and community-based distribution to promote contraceptive use, and important factors to include to ensure comparability of findings. Such studies have already aided family planning program decisions. Several ways that cost-effectiveness analysis can be improved in practice to make it most useful include: 1) all inputs must be included, 2) services and methods need to be evaluated, 3) cost per acceptor should be relied on less, 4) user characteristics must be taken into account, and 5) anticipating cost-effectiveness analysis, the data needed should be built into the project at the planning stage.^ieng

A comparative description of infant feeding practices in Zaire, the Philippines and St. Kitts-Nevis.

PIP: Infant feeding issues and research commonly portray infant feeding practices as a dichotomous variable; i.e., breastfeeding vs. bottlefeeding. This research establishes the complexity and variability in infant feeding patterns in 3 sites in the developing world. Comparative data are presented on the modes and products used to feed infants in Kinshasa, Zaire; St. Kitts-Nevis, West indies; and Cebu City, Philippines. They demonstrate that in these areas most infants receive some breastmilk. Bottlefeeding is also common but is rarely the exclusive mode of feeding. And the prevalence, manner of use, and role of the bottle varies among the 3 sites. Early supplementation of breastmilk by a variety of liquids, semisolids, and solids is typical of all 3 areas. These findings have important implications for educators and policymakers, as well as for research efforts relating infant feeding practices to infant health outcomes.^ieng

WHO collaborative study on breast feeding.

WHO, concerned with the declining breast feeding rate in developing countries, has organized investigations in nine different countries of different aspects of breast feeding and breast milk with the ultimate aim of formulating programmes of intervention. The basic epidemiological study on 24000 mother/child pairs is just completed and some preliminary data are reported on the pattern of breast feeding in the three studied socio-economic groups--urban elite, urban poor and traditional rural--which differ significantly in their breast feeding rate as well as in the pattern of return of menstruation in breast-feeding and non-breast-feeding mothers.

PIP: Concerned with the declining breast-feeding rate in developing countries, WHO has organized investigations in 9 different countries of different aspects of breast-feeding and breast milk with the ultimate aim of formulating programs of intervention. The basic study was begun in 1975 and concentrated on the epidemiology of breast-feeding among 3 different socioeconomic groups, the urban elite, urban poor, and traditional rural. 9 countries, Chile, Guatemala, the Philippines, India, Ethiopia, Nigeria, Zaire, Sweden, and Hungary, participated in the study, and altogether almost 24,000 mother/child pairs were involved. Data from all 9 countries have now been compiled, and are being centrally analyzed. Results of a few of the important preliminary findings are reported here. As far as duration of breast-feeding is concerned, significant differences are appearing between the 3 different socioeconomic groups in each country. In most settings, it is apparent that breast-feeding declines most rapidly among the urban elite group and is most prolonged in the rural traditional populations. The preliminary data corroborate the long-held position that postpartum amenorrhea is more prolonged in breast-feeding than in non-breast-feeding mothers. The breast-feeding development in Sweden is contrasted with that in Guatemala, and marked differences are noted in breast-feeding patterns. It was felt that once the various factors influencing breast-feeding patterns are better understood, the specific action and intervention program suitable to each country and setting could be initiated to improve infant nutrition. The action program thus developed would be more effective and efficient since it would be addressed specifically to the factors influencing breast-feeding and infant feeding in a given area.

News, views, trends: a world-wide survey of recent developments, fresh ideas and production plans.

PIP: Recent developments in the tobacco industry in several countries are described: 1) in the USSR the policy is not to encourage smoking but to produce pleasant cigarettes which are as harmless as possible; 2) in the US, a survey shows that in 1975 not more than 12.4% of men over age 21 smoked a pipe; 3) in Britain a new cigarette tax structure will cripple the cigarette industry's coupon scheme of which manufacturers make great use to secure brand loyalty; 4) in the Philippines a proposal to print a health warning on cigarette packets and in advertisements might affect cigarette and tobacco taxes, which contribute 47% of government income; 5) in the Netherlands health warnings will be printed on cigarette packs, 6) in Austria there has been an increase of 4.2% in cigarette smoking since late 1975; 7) in Poland anti-smoking officials have proposed that the name of the popular "Sport" cigarette be changed; 8) in Indonesia there has been a recovery in kretek sales; 9) in Denmark cigarette consumption increased 6% from 1974; and 10) in western Europe it has been shown that up to 99% of grocery stores in Ireland sell tobacco products, 91% in Britain, 30% in Austria, 17% in Spain, and 7% in Italy.^ieng