Macrophage Biology in Human Granulomatous Skin Inflammation.

Cutaneous granulomatoses represent a heterogeneous group of diseases, which are defined by macrophage infiltration in the skin. Skin granuloma can be formed in the context of infectious and non-infectious conditions. Recent technological advances have deepened our understanding of the pathophysiology of granulomatous skin inflammation, and they provide novel insights into human tissue macrophage biology at the site of ongoing disease. Here, we discuss findings on macrophage immune function and metabolism derived from three prototypic cutaneous granulomatoses: granuloma annulare, sarcoidosis, and leprosy.

Biology and physiology of Hanseniaspora vineae: metabolic diversity and increase flavour complexity for food fermentation.

Apiculate yeasts belonging to the genus Hanseniaspora are predominant on grapes and other fruits. While some species, such as Hanseniaspora uvarum, are well known for their abundant presence in fruits, they are generally characterized by their detrimental effect on fermentation quality because the excessive production of acetic acid. However, the species Hanseniaspora vineae is adapted to fermentation and currently is considered as an enhancer of positive flavour and sensory complexity in foods. Since 2002, we have been isolating strains from this species and conducting winemaking processes with them. In parallel, we also characterized this species from genes to metabolites. In 2013, we sequenced the genomes of two H. vineae strains, being these the first apiculate yeast genomes determined. In the last 10 years, it has become possible to understand its biology, discovering very peculiar features compared to the conventional Saccharomyces yeasts, such as a natural and unique G2 cell cycle arrest or the elucidation of the mandelate pathway for benzenoids synthesis. All these characteristics contribute to phenotypes with proved interest from the biotechnological point of view for winemaking and the production of other foods.

Bringing physics to bear on the phenomenon of life: the divergent positions of Bohr, Delbrück, and Schrödinger.

The received view on the contributions of the physics community to the birth of molecular biology tends to present the physics community as sharing a basic level consensus on how physics should be brought to bear on biology. I argue, however, that a close examination of the views of three leading physicists involved in the birth of molecular biology, Bohr, Delbrück, and Schrödinger, suggests that there existed fundamental disagreements on how physics should be employed to solve problems in biology even within the physics community. In particular, I focus on how these three figures differed sharply in their assessment of the relevance of complementarity, the potential of chemical methods, and the relative importance of classical physics. In addition, I assess and develop Roll-Hansen's attempt to conceptualize this history in terms of models of scientific change advanced by Kuhn and Lakatos. Though neither model is fully successful in explaining the divergence of views among these three physicists, I argue that the extent and quality of difference in their views help elucidate and extend some themes that are left opaque in Kuhn's model.

Risk analysis. HIV / AIDS country profile: Zambia.

PIP: The World Health Organization (WHO) estimates that, as of the end of 1994, 17% of adults in Zambia had been infected with HIV. The Ministry of Health's National AIDS/STD/TB and Leprosy Program's (NASTLP) prevalence estimates concur with those of the WHO. NASTLP surveillance covers women attending antenatal clinics, outpatients, and blood donors. Although available HIV prevalence data for the country are less than reliable, it is clear that HIV prevalence has increased over time to presently high levels and that prevalence is higher in urban areas than in rural areas. Very high levels of HIV prevalence have been found among some health care professionals tested at Lusaka University Teaching Hospital. The data on AIDS cases are of poor quality. 42% of urban and 33% of rural households in 1993 contained orphans. Projections of the course of the epidemic are presented along with discussion of the potential impact upon the economy, the agricultural sector, and the private sector. Zambia's background is outlined. Vulnerability is then considered with regard to sexually transmitted diseases, poverty, the loss of formal sector employment and structural adjustment programs, mobility within society, urbanization, social pressure upon girls to have sexual intercourse, and the traditional practice of cleansing surviving spouses through sexual intercourse with an in-law. Government and private sector responses and external assistance from the European Commission are noted.^ieng

Tuberculosis prevention: where do we go from here?

PIP: The Karonga (Malawi) Prevention Trial revealed that repeat BCG vaccinations did not protect against pulmonary tuberculosis (TB) but appeared to provide some protection against glandular TB. They increased protection against leprosy. In fact, a single BCG vaccination conferred 50% protection against leprosy and a repeat BCG vaccination increased protection by another 50%. This trial's findings confirm the need for maintaining BCG vaccination programs in countries where leprosy is a public health problem, for individuals at high risk of leprosy (i.e., contacts of leprosy cases), and because BCG provides some protection against severe forms of TB (i.e., miliary disease and TB meningitis). An alternative TB vaccine needs to be developed, however. The protective efficacy of BCG against pulmonary TB is higher at latitudes far from the equator (80% in northern Europe vs. 0% in India and Malawi). It appears that the immunologic effects of environmental mycobacteria compromise BCG's protective effect against pulmonary TB. There is heterologous immunity between various mycobacterial infections. Low-level delayed-type hypersensitivity (DTH) to tuberculin in non-BCG vaccinated people reflects exposure to environmental mycobacteria. These people are at lower risk of TB than are people with either no DTH or strong DTH to tuberculin. Intradermal exposure to different mycobacteria provides varying degrees of protection against TB in guinea pigs. The warmer and the wetter the environment, the more widespread is colonization by mycobacteria. An area of future research is mapping the distribution of environmental mycobacteria, correlating it with the pattern of DTH responses to tuberculin, and then laboratory work to isolate relevant antigens of the mycobacteria. Another approach is identifying mycobacterial antigens that elicit protective immune responses in vitro so researchers can then identify which antigens and responses are associated with patterns of DTH known to reflect low risk of TB and which response patterns are elicited by BCG against leprosy but not TB antigens. New vaccines are not on the imminent horizon, however.^ieng

India's vaccine inventor: Gursaran Talwar.

PIP: Dr Gursaran Talwar, 68, has worked for almost 20 years to find a safe, long-lasting, and reversible contraceptive vaccine. The Director of India's National Institute of Immunology began his research in the mid 1970s with financial support from the Indian government and IDRC. Toxicology studies were conducted for 10 years. The vaccine increases production of antibodies against human chorionic gonadotropin (HCG), a hormone which assists in preparing the uterus for embryo implantation. The vaccine blocks this process and prevents pregnancy. Without the vaccine, 50-75% of embryos fail to be implanted because of antibodies to HCG; with the vaccine, 100% do. The vaccine is administered once a month for 3 months. Although another form of contraception must be used during this time, protection afterwards lasts for a year. Boosters are given annually. In a clinical study of 88 vaccinated women, 1 pregnancy occurred in 821 menstrual cycles. Fertility returns with discontinuation of the vaccinations. Dr Talwar is also working on a contraceptive for the 3-month period using the purified extract of the neem tree, a male contraceptive, a treatment for prostate cancer, and a vaccine against leprosy.^ieng

Leprosy: an urgent need to step up use of MDT in Africa.

PIP: 10-12 million people in the world have leprosy. India claims about 4 million of these cases. Overall at least 20% of the cases are children. In the 1940s, dapsone was the only drug used to treat leprosy. By the early 1970s, dapsone did not perform as expected and Mycobacterium leprae were beginning to exhibit resistance to dapsone. In 1982, WHO published results of its study which recommended fixed and relatively short duration regimens of multiple drug therapy (MDT) for all people with leprosy. It also listed recommendations on diagnosis, classification, and distribution of patients to either pauci or multibacillary groups. MDT depends on what type of leprosy patients have. For example, patients with multibacillary leprosy receive rifampicin, clofazimine, and dapsone whereas those with paucibacillary leprosy receive only rifampicin. In many African countries, however, MDT is not used. Yet cases of leprosy exist in 94% of Africa's countries. Moreover 37% have highly prevalent leprosy and the lowest percentage of patients on MDT (18% vs. world average of 56%). In fact, Nigeria is included in the group of 5 countries with 84% of all cases. Until the various countries in Africa can satisfy the ideal requirements for establishing a MDT program, they should begin MDT at least on a small scale. They do need, however, an adequate supply of the drugs. The other requirements include a good plan of action, laboratory facilities, transport, and referral centers. If the period of time needed to meet these requirements is long, then physicians should conduct pre MDT screenings to diagnose cases and determine who needs chemotherapy. The best way to diagnose cases is from clinical experience and paying particular attention to dermatological and neurological findings. Early identification is needed since leprosy cases are stigmatized. This article includes MDT dosages in adults and children.^ieng

Care and development of children in tribal areas.

PIP: About 53 million people (8% of the population) of India belong to various tribes in about 400 tribal communities. These groups live in different ecological geoclimatic conditions throughout India ranging from the Sub-Himalayas to the islands in the Bay of Bengal and in the Arabian Sea. They also differ in distinct biological traits and cultural and socioeconomic background. Due to cultural patterns which vary from tribe to tribe, they are all at different stages of social, cultural, and economic development. Since the tribes live in isolated and inaccessible areas, it is hard to implement health care and nutrition activities, elementary education, and preventive promotive health care. The government does plan to provide rural day care for 0-3 year old children. The Integrated Child Development Services (ICDS) Scheme reaches 2197 of 5143 tribal development blocks. ICDS activities include immunization of children and mothers, health education, and supplementary nutrition. The government also promotes primary health care in tribal areas. Despite these efforts, child welfare and development in tribal areas have not improved. Recently nongovernmental organizations have joined child welfare and development efforts in tribal areas. The Jigyansu Tribal Research Center has compiled a long list of recommendations to improve child welfare and development efforts in tribal areas including improving preventive activities especially those that target specific local diseases such as cerebral malaria and leprosy, introduction of traditional herbal medicines, and comprehensive data collection.^ieng

AIDS in Africa--an update.

PIP: At least 1 million people in Central and East Africa are infected with HIV-1, and there are 10,000 new cases of AIDS per year. HIV-1 is spreading into the Ivory Coast, Ghana, Mozambique, Angola and southern Africa. HIV-2 is prevalent in West Africa, particularly Senegal and Guinea-Bissau. Groups at greatest risk for HIV-1 are prostitutes, their customers, and patients with a history of sexually-transmitted diseases, which cause breaches in mucosal epithelium. 24% of pregnant women in Uganda are infected, and the risk of transplacental infection is estimated to be between 17% and 79%. Blood transfusion is the 3rd most frequent mode of infection, largely due to need for blood by anemic women. Repeated pregnancy is a cofactor in the progression of AIDS, and infected infants suffer intrauterine growth retardation, premature birth, low birth weight, and high mortality in the 1st week of life. AIDS in adults is often accompanied by tuberculosis, herpes zoster, hepatitis B, herpes type 2, and leprosy. Clinical diagnosis of AIDS is made by enzyme-linked immunosorbent assay, but African patients have a high frequency of anti-p24 antibody which masks the p24 antigenemia. Some African countries have AIDS education programs, condom distribution and blood screening, but AIDS control programs need to be integrated with primary health care.^ieng

Effect of oral contraceptives on urinary porphyrins.

PIP: Several studies have reported on the appearance of cutaneous porphyria in people treated with estrogen. This study was undertaken to investigate the effects of oral contraceptives (OCs) on levels of porphyrins in urine in nonporphyric women. 30 women aged 21-40 and on OCs were observed as the study group, and 10 women using other contraceptive methods were observed as the control group. Urinary porphyrins were measured by the Remington method. Levels of urinary coproporphyrin and of urinary uroporphyrin were higher in the study group than in the control group. These differences, however, are not statistically significant. To study the effect of duration of OC treatment, women who had taken OCs for 3-6 months and women who had taken OCs for longer than 6 months were observed, and the means of urinary coproporphyrin and uroporphyrin measured. Again, the differences were found to be insignificant, although slightly higher values of urinary coproporphyrin were obtained for women who had been on OCs for a longer period. These results compare favorably with others reported in the published literature. It can be concluded that OC treatment has no significant bearing on porphyrin metabolism.^ieng