Organic nanofibers containing insect pheromone disruptants: a novel technical approach to controlled release dispensers with potential for process mechanization.

Beginning fifty years ago, the search for suitable dispensers containing insect pheromones grew with the availability of these synthetic biotechnical tools. Many economic entomologists and application engineers dearly wish they had the "smart, intelligent and ideal dispenser". More or less suitable approximations are available commercially, but none so far meets all demands. Under economic strictures, novel inexpensive systems would be advantageous with release characteristics tailored to the specific life histories of pest insects, the plants considered and the numerous requirements of growers alike. Simultaneously, their field distribution should be mechanizable and be accomplished by one (or very few) application runs. The dispensers should be biodegradable, biocompatible, sustainably applicable, and they should be based on renewable resources. This report presents first results of a novel organic, electrospun nanofiber dispenser with dimensions in the upper nanometer range. Its load of pheromone can be adjusted to be sufficient for 7 weeks of constant disruptive action in vineyards and can be directed against the European Grape Vine Moth Lobesia botrana (Lepidoptera: Tortricidae) which here serves as a readily available model. Mating disruption in L. botrana and the related Eupoecilia ambiguella is a well studied and developed engineering process. Equally, nanofiber production by electrospinning (for a comprehensive review see Greiner and Wendorff, 2007A, B) is well known and already has numerous applications in filtration technology, air conditioning, and medical wound dressing. Our goal was to bring together and successfully mate these (partly incompatible) technologies via technical tricks of a proprietary nature. Even though the lifetime and effectiveness of currently available nanofibers still must be doubled, the rather complicated system of their production and analysis is known well enough to identify the parameters that need future adjustment. Another challenge is the mechanical distribution of the fibers in the vineyards by suitable machinery. Also, in this respect, certain technical leads are available for future development.

Primary and acquired drug resistance in adult black patients with tuberculosis in South Africa: results of a continuous national drug resistance surveillance programme involvement.

Drug resistance is a major problem in the treatment of tuberculosis, and monitoring programmes are essential in control of this disease. The extent of primary resistance in a community is an important indication of the effectiveness of treatment schedules. Since 1965 the Tuberculosis Research Institute (TBRI) of the South African Medical Research Council has performed 25 annual surveys of drug resistance in adult black tuberculosis patients where the disease is most prevalent. Methodology for patient selection, specimen collection, laboratory procedures and criteria for drug resistance were strictly adhered to. All specimens were processed in a central laboratory supervised by the same two technologists. Between 1965 and 1988 a total of 33,111 strains of Mycobacterium tuberculosis were isolated from new cases and 19,134 from old cases. Both primary and acquired resistance to the 5 major antituberculosis drugs has decreased dramatically. Sex and age do not influence resistance rates, while patients' ethnic origin and geographical location do. The results indicate that current tuberculosis treatment practices are satisfactory. The prevalence of primary drug resistance in black South Africans is now intermediate between those countries where eradication of tuberculosis is well advanced and those where the disease remains a public health problem. Also, it can be shown that comparable and clinically significant data can be obtained from a central laboratory employing unsophisticated and inexpensive drug susceptibility testing procedures.

Mononuclear leucocyte function in patients with lichen planus and cutaneous lupus erythematosus during chemotherapy with clofazimine.

Mitogen-induced transformation and the production of reactive oxidants by mononuclear leucocytes (MNLs) from patients with chronic dermatological disorders were investigated in vitro before and during the administration of the antimycobacterial/immunosuppressive agent clofazimine (200 mg 3 times weekly). Seven patients, 4 with lichen planus and 3 with cutaneous lupus erythematosus, were included in the study. Clofazimine administration did not influence the mitogen-induced proliferative responses of patients' MNLs. However, chemotherapy with this drug stimulated the production of reactive oxidants by MNLs. Since reactive oxidants are immunosuppressive it is possible that these effects may be involved in the pharmacotherapeutic activity of clofazimine.

Pulmonary tuberculosis treated with isoprodian and rifampicin or pyrazinamide.

Three regimens of 9 months' duration, 2 containing Isoprodian (isoniazid, prothionamide and dapsone) and either rifampicin or pyrazinamide and the third, a former standard regimen, isoniazid, streptomycin and pyrazinamide, were allocated at random to 436 untreated African tuberculosis patients. In the course of the trial 83 were excluded for various reasons and 93 were lost. After 3 months of hospitalization, patients took either Isoprodian or isoniazid at home for 6 months and were then followed up for 24 months. The Isoprodian plus rifampicin regimen achieved 97% bacteriological cure, the Isoprodian plus pyrazinamide regimen 86% and the standard regimen 91%. Of 35 patients found to harbour drug-resistant strains 22 were cured. There were 15 relapses in all. Absconding was the most common cause of failure.

Glucocorticoid-induced lymphoma cell death: the good and the evil.

Glucocorticoid hormones and their synthetic derivatives are widely used in therapy due to their strong anti-inflammatory and immunosuppressive potential. While the molecular basis of the anti-inflammatory action is to date at least partially understood, knowledge regarding the mechanism underlying glucocorticoid effects on the immune system is rather fragmentary. The immunosuppression could be attributed to at least two distinct processes: inhibition of the production of growth mediators and glucocorticoid-induced cell death. The mechanism of glucocorticoid-induced cell death can be divided into two steps, a reversible growth inhibition and cell lysis. The first step is characterized by many metabolic alterations typical of the catabolic potential of corticosteroids. After a delay of several hours activation of an endonuclease appears to initiate the lytic phase. By the action of this endonuclease the DNA is fragmented. In opposition to the chromatin damage, poly(ADP-ribosyl)ation is activated in order to stabilize the chromatin structure until the antagonistic potential is exhausted and the cells die. Therefore it can be speculated that the lethal event in glucocorticoid-induced cell death is a destruction of the regular chromatin structure.

The tolerability and efficacy of a 6-month antituberculosis regimen containing rifampicin, isoniazid and pyrazinamide.

The tolerability and efficacy of a 6-month daily regimen of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) were tested in 130 hospitalized patients, mostly Black, with previously untreated pulmonary tuberculosis. PZA was discontinued at the end of the 2nd month. In 6 cases treatment was discontinued because of drug intolerance. The symptoms were severe rash, mild thrombocytopenia, deteriorating haematological and renal condition and in the remaining 3 patients hyperbilirubinaemia. Of the 125 patients who could be assessed bacteriologically, 110 were infected with organisms which were fully susceptible to INH and RMP, and 95% of their cultures and 77% of their smears had converted to negative after 2 months of treatment. Similar results were obtained for all but 2 of the 15 patients with drug-resistant bacilli. Cavitation of the lungs was reduced in 78% of the patients and the extent of other tuberculous lesions diminished in 87%.

Epidemiology of mycobacteria other than tubercle bacilli in South Africa.

The findings of the last two decades in the area of the epidemiology of mycobacteria other than tubercle bacilli are reviewed. The veterinary problem of cross-reactivity in cattle to the tuberculin test was overcome by comparative use of avian purified protein derivative (PPD). Outbreaks of mycobacterial lymphadenitis in swine occur sporadically and are due to Mycobacterium intracellulare. The reservoir for nontuberculous mycobacteria appears to be in the environment, especially on growing fodder plants; water cannot be incriminated. In humans very few cases of mycobacteriosis have been found. However, countrywide surveys of random sputum cultures have shown that exposure of rural people to Mycobacterium avium-intracellulare is either continuous or frequent. Ten percent of African children react specifically to avian PPD tuberculin. No direct influence of this exposure on the incidence of tuberculosis can be seen. No protective effect by mycobacteria other than tubercle bacilli is postulated.

Follow-up tuberculosis prevalence survey of Transkei.

After 5 years a follow-up prevalence survey was conducted in Transkei on a randomly selected sample of the rural population. The parameters investigated were bacteriological prevalence of tubercle bacilli in sputum, radiological prevalence of chest abnormalities associated with tuberculosis in adults, and hypersensitivity to tuberculin in children. Bacteriological positivity was 2.1% on smear microscopy and 4.3% on culture. Radiological evidence of tuberculosis was demonstrable in 12.5% of subjects, of whom 8.7% were considered active and 3.8% inactive. The mean prevalence of tuberculin positivity according to the Mantoux test was 30.1%. An annual risk of infection of 4% was calculated, showing a continuous decrease of 5% per year on the 7% risk of infection encountered in 1972. Compared with the first survey, a general reduction in prevalence of tuberculosis is evident.

First tuberculosis prevalence survey in KwaZulu.

The results of a prevalence survey undertaken during 1974 are presented. A stratified 3-stage sampling technique was used to select 3 789 people from 10 randomly chosen sites in KwaZulu. One Heaf test and 2 Mantoux tests were performed on each of 1 769 children under 18 years of age, of whom 28,7% were found to have BCG scars. Of the radiographs taken of persons 15 years of age and older, 893 were found to be negative, 25 (2,7%) disclosed active tuberculosis (TB) and 3 (0,3%) miliary TB. Of the 1 136 sputum specimens collected and examined by fluorescence microscopy, 15 (1,3%) were found to be positive and 9 of them were confirmed by culture. Culture of 1 149 specimens yielded 9 (0,8%) isolations of Mycobacterium tuberculosis and 17 strains of other mycobacteria. The annual rate of infection was calculated at 1,4% by applying Styblo's epidemiological model, and a downward trend was indicated. A follow-up survey after 5 years is needed to confirm this trend.

Comparison of isoniazid phenotyping of black and white patients with emphasis on South African blacks.

Black tuberculosis patients from South Africa (S. A.) as well as from Birmingham, Alabama, U.S.A., showed a higher percentage of fast inactivators of isoniazid (INH) than that found in the North American white population, simultaneously sampled. In S. A. blacks, the frequency of fast inactivation was 57.9--59.6%, while in American blacks of Birmingham it amounted to 60.3%; in comparison to the above groups the rate of fast acetylators in Canadian Caucasians was 41.9% and in the USA white population 41.0%. For phenotyping of isoniazid inactivators a urine test was used. In this method the concentrations of INH (including isoniazidhydrazones) as well as acetylisoniazid were determined in the specimens collected 6--8 hrs following a test dose of 10 mg/kg INH.

Phenotyping of South African black tuberculosis patients for inactivation of isoniazid.

Studies of isoniazid inactivation rates in black tuberculosis patients from South Africa and Birmingham, Alabama, showed a higher frequency of fast inactivation than those of North American Caucasian patients. After an oral test dose of 10 mg/kg isoniazid the percentage of fast inactivators in black patients of South Africa and Alabama was close to 60% while in North American white participants (Canadian and Birmingham Caucasians), the frequency of fast inactivation was approximately 40%.

Tuberculosis in laboratory animals.

Tuberculosis can cause great losses in captive colonies of various animal species. In South Africa the culprit is the human type of tubercle bacillus. Interspecific transmission of tuberculosis infection amongst laboratory animals, notably primates, is known to occur, and often handlers and caretakers act as the source of infection. The need for preventive measures in laboratory colonies and procedures for case finding and treatment of tuberculous animals are discussed. Indiscriminate destruction of diseased animals is opposed. The South African situation as revealed by questionnaire survey is described.

The significance of the tuberculosis infection risk and its application in Pretoria.

The value of the infection risk index for the determination of the TB situation and for the planning and evaluation of specific control measures is discussed. From tuberculin studies performed on schoolchildren in Pretoria since 1972, the annual risk of contracting a TB infection or of reinfection has been determined for all races in Pretoria; it is 0,05% for Whites, 0,53% for Coloureds, 0,68% for Asians, and 0,64% and 1,05% for Blacks in Atteridgeville and Mamelodi respectively. A downward trend of the risk could be shown for all population groups.

Evaluation of BCG vaccines and a new method of multipuncture administration.

In comparative investigations the Japanese vaccinating tool was found to be more satisfactory for BCG administration than the Heaf multipuncture apparatus. Not only were the immune responses achieved by 27 punctures made by the Japanese applicator equal to those produced by 40 punctures made by the Heaf apparatus, but the results were similar to those obtained with the intradermal method of vaccination. The Japanese applicator can be sterilized effectively, it is simple to use, durable, usable up to 100 times and cheap. All pre- and post-vaccination tuberculin testing was done intradermally with 2 tuberculin units of human PPD RT23. The studies also confirmed the high quality of the Japanese intradermal and percutaneous BCG vaccines. Administration of the potent percutaneous Japanese BCG vaccine with the Japanese applicator is an ideal, effective and safe method of BCG vaccination.

Pulmonary disease associated with mycobacteria other than tubercle bacilli in miners.

Five patients with lung disease caused by mycobacteria other than tubercle (MOTT) bacilli are described. Mycobacterium kansasii was the causative organism in 4 patients and M. scrofulaceum in 1 patient. The species were repeatedly isolated from sputum specimens cultured on Löwenstein-Jensen medium. The clinical features, mycobacterial isolations, bacteriological properties of the pathogens and the therapeutic problems encountered are discussed.