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Biomedical subjects

T A Freyvogel

Publications and source records attributed to T A Freyvogel.

At least 19 recordsLinked to original sources

Scientific research partnership: north-south and south-south.

Scientific research can contribute much to solving many urgent global problems. However, research must be conducted in a global context and, in particular, must be extended to the countries of the South. If this is to be done, the research capacities of those countries must be considerably expanded and consolidated. Swiss strategy for promotion of research in the developing world is primarily devoted to this aim. Problems of general concern must be solved by joint efforts, which means in development-oriented, long-term, interdisciplinary research partnerships. In this context the requisite training of everybody involved can be conducted in a continuous way. Partnership is a severely taxing activity. In six points it is shown that today the greater portion of the Swiss research community does not yet meet these requirements. Despite relatively scarce funds, the time has come to review the Swiss university world in this respect also.

Developing Countries↗

Purification and characterization of three alpha 2-antiplasmin and alpha 2-macroglobulin inactivating enzymes from the venom of the Mexican west coast rattlesnake (Crotalus basiliscus).

Three distinct alpha 2PI (alpha 2-antiplasmin) degrading and alpha 2M (alpha 2-macroglobulin) inhibiting enzymes, named proteinase a, b and c, have been purified from the venom of Crotalus basiliscus (the Mexican west coast rattlesnake) by fast protein liquid chromatography (anion-exchange chromatography and gel filtration chromatography). SDS-PAGE revealed that proteinase a and b had similar mol. wts (approximately 23,500), whereas proteinase c displayed a mol.wt of approximately 24,200. Their isoelectric points were found to be acidic, ranging from pH 4.8 to 5.7. The proteinase activity of all three enzymes was inhibited in the presence of EDTA. Dependent on enzyme concentration, a progressive and catalytic inactivation of alpha 2PI was induced, leading to an almost complete loss of the plasmin inhibitory activity at a molar ratio of enzyme: alpha 2PI = 0.1 within 60 min. The ability of alpha 2M to protect the esterolytic activity of trypsin from inhibition by soybean trypsin inhibitor was only reduced at a molar ratio of enzyme: alpha 2M = 0.5, whereas no inactivation could be observed when the three venom proteinases were incubated with an excess of alpha 2M, suggesting that the inactivation occurred by complex formation but not by degradation of the intact alpha 2M molecule. In SDS-PAGE, inactivation of human alpha 2PI (mol. wt 68,000) correlated with the appearance of two cleavage products with an approximate mol. wt of 56,000 and 11,000, respectively. The three proteinases had no thrombin-like activity. Plasminogen and factor X were not activated and no platelet aggregation was induced. They degraded the A alpha- and B beta-chain of fibrinogen and showed plasma extravasation-inducing activity following intradermal injection into the abdominal skin. None of the enzymes showed any activity against a series of chromogenic p-nitroanilide substrates.

Animals↗

Purification and characterization of an antithrombin III inactivating enzyme from the venom of the African night adder (Causus rhombeatus).

A serine proteinase was isolated from the venom of the night adder (Causus rhombeatus) by fast protein liquid chromatography (anion-exchange, gel filtration and hydrophobic interaction). The protein (termed CR-serpinase) had an estimated mol. wt of 45,500 as determined by SDS-PAGE, pI of 4.7 and a carbohydrate content of 18.9%. Incubation of CR-serpinase with purified human antithrombin III at a molar ratio of 1:66 resulted in a loss of more than 90% of the initial AT III activity within 10 min. The reaction was dependent on heparin. In SDS-PAGE inactivation of human antithrombin III was correlated with the occurrence of two cleavage products. The cleavage site in the antithrombin III molecule was determined to be Arg 393-Ser 394 by amino-terminal sequencing. CR-Serpinase had no thrombin-like activity since no fibrinogen conversion was induced and had no procoagulant activity. CR-Serpinase activity was not inhibited by antithrombin III-heparin and was not decreased by a 10-min preincubation in normal human plasma. Inactivation of antithrombin III by CR-serpinase appeared to be very specific.

Amino Acid Sequence↗

Antigenic relationship between the venom of the night adder Causus maculatus and venoms of other viperids.

Monovalent antivenoms were raised in mice against the venoms of Causus maculatus, Vipera ammodytes, Echis carinatus, Cerastes cerastes, Bitis arietans, Agkistrodon rhodostoma and Bothrops atrox. These antivenoms as well as four commercially available antivenoms were tested against the venoms of 15 viperid species by means of immunoelectrophoresis and/or ELISA. Cross-reactive protein bands were determined by immunoblot. ELISA cross-reactions of C. maculatus antivenom were low with all heterologous venoms. When investigating the other viperine antivenoms in ELISA stronger cross-reactions were observed with several heterologous venoms. In immunoblot, two heterologous antivenoms cross-reacted with one or two protein bands of C. maculatus venom whereas there were at least four heterologous antivenoms cross-reacting with each of the other venoms. The findings indicate that there is little antigenic affinity between C. maculatus venom and the other venoms investigated. Broad in vitro cross-reactions between viperine antivenoms and Causus venom which were reported in literature seem to be attributable to the use of antivenoms of commercial grade. Specificity of commercially produced, mono- or polyvalent antivenoms may not be strictly limited to those venoms, against which potency is claimed on the label of the product.

Animals↗

Antibodies to the repetitive epitope of Plasmodium falciparum circumsporozoite protein in a rural Tanzanian community: a longitudinal study of 132 children.

An ELISA employing a novel synthetic peptide consisting of 40 (Asn-Ala-Asn-Pro) repeats of Plasmodium falciparum circumsporozoite protein, (NANP)40, was used to detect antibodies against P. falciparum circumsporozoite protein in 132 children, 1 month to 15 years old, from a rural community (Kikwawila village) of Tanzania, a region where malaria is hyperendemic. The children were surveyed comprehensively over 3 consecutive years for clinical, parasitological, and serological parameters. Entomological data were also gathered for selected households in this village. The following results were obtained: anti-(NANP)40 antibodies increased as a function of age; the majority of children over 10 years showed a stable positivity for such antibodies during the longitudinal study; a negative correlation was observed between the levels of anti-sporozoite antibodies and both spleen enlargement and the presence of parasites in thick smears; no relationship was found between anti-(NANP)40 antibodies and asexual blood stage antibodies; children living in two representative households with comparable indoor resting mosquito densities showed markedly different frequencies of anti-(NANP)40 antibodies, in spite of comparable clinical, parasitological, and serological parameters. Thus, in addition to the exposure to infectious mosquito bites, other (e.g., genetic) factors, may play a role in the ability of certain individuals to mount an antibody response against this immunodominant repetitive epitope. The results presented in this paper confirm that the (NANP)40-ELISA represents a simple, reliable means for the detection of anti-(NANP)40 circumsporozoite protein antibodies and suggest that such antibodies may contribute to the immune protection against malaria in humans.

Adolescent↗

Longitudinal study on the health status of children in Kikwawila village, Tanzania: study area and design.

The paper describes the study area and the project design of a longitudinal study on the health status of children undertaken in Kikwawila village in southeastern Tanzania from 1982 to 1984. This rural village is situated in the Kilombero river plain (270 m above sea level) and extends over 50 km2. A census in 1982 (repeated in 1984) revealed that 1152 (1406) people lived in 260 (299) households of the nucleated roadside settlements of the sectors Kikwawila and Kapolo. The vital statistics showed an infant mortality rate estimate of 198/1000 which was far above the regional (140%) and the national (137%) averages. Over 30 tribes were recorded but 6 tribes formed 84% of the population. The population was predominantly muslim (75%). Most adult inhabitants (90%) were subsistence farmers cultivating an average of 3.7 acres per household. Rice, maize and cassava were the main crops of the area. At the beginning of the study, the village had no village health post, dispensary or health centre and it lacked an adequate and safe water supply. A great proportion of the population (67%) had to rely on water from unprotected hand dug wells and from rivers for domestic purposes. Only half of the households had a simple pit latrine. Even when latrines were present, they collapsed after heavy rains due to loose, unconsolidated soils, termites and the high water table. These difficulties affected the sustained success of sanitation campaigns. The study area represented a typical settlement of the Kilombero valley and was, with regard to most demographic, ethnic, agricultural and health characteristics, considered a suitable pilot area. A primary health care programme based on village health workers was implemented in parallel with complementary community based studies on the causes, interrelations and control measures of the major health problems faced by the community, and possible control measures.

Age Factors↗

Agricultural production in Kikwawila village, southeastern Tanzania.

Food production, land utilisation and agricultural structures were surveyed at Kikwawila village, north of Ifakara (Kilombero District, Morogoro Region) in 1984. This study was part of a more comprehensive, longitudinal programme to investigate the health status of a rural community, aiming in particular at the interrelations between nutrition, parasitic infections, immunity and the environment. Out of 340 households, 100 were interviewed and their subsistence farming activities recorded. The soil was found to be of great variability, being fertile where it was of alluvial origin but of reduced potential where it was non-alluvial. In all, 70 plant species were registered as being cultivated, with rice, maize, cassava and beans providing the main staple food. Apart from a few exceptions, the fields were cultivated without any mechanization. The seasonal distribution of agricultural work is described, but no detailed workload analysis of the villagers with regard to age and sex has been performed. At the foot of the mountains, where artificial irrigation has been introduced, dry season cropping was practised in addition to the prevailing wet season farming, which rendered the cultivation of marketable crops (mainly tomatoes) possible. The farmers were found to be imaginative and capable of adapting to various conditions, irrespective of their tribal origins. Alternatively, the quality of the soil and the unreliable availability of water set limits to the potential of food production in the area. Although land is still available, it is becoming more scarce as the human population increases. The further impoverishment of the land represents an imminent danger. Therefore, top priority ought to be given to soil conservation, followed by intercropping and/or crop rotation, seed production and crop protection against game and pests. Means of implementing such measures are discussed. It is suggested that Community Agricultural Workers be installed, elected by the villagers and trained to establish the link between the existing agricultural extension service and the farmers' communities.

Agriculture↗

Laboratory and field trials at Ifakara (Kilombero District, Tanzania) on the plant molluscicide Swartzia madagascariensis.

The molluscicidal activity of crushed seed pods of Swartzia madagascariensis was assessed by laboratory and field trials. Mature dry seed pods were ground and extracted in tap water for 24 h. Water extracts exerted a significant molluscicidal activity against Bulinus globosus up to dilutions of 100 mg of ground pods per litre. The chromatographically isolated saponin (1) responsible for the molluscicidal activity showed a toxicity of LC 100 at 3 mg/l after exposure of B. globosus and Biomphalaria glabrata for 24 h. Saponin (1) could be identified by FAB-MS and 13C-NMR-spectroscopy as oleanolic acid-3-O-beta-D-glucuronopyranosyl (1----3)-alpha-L-rhamnopyranoside. Two field trials with S. madagascariensis pod extracts in ponds (60 and 160 m3) harbouring dense populations of B. globosus compared well with the laboratory findings and showed the efficiency of the molluscicide in a natural habitat. A single application of the plant molluscicide significantly reduced the populations of B. globusus. The toxicity of S. madagascariensis pod extracts to non-target organisms remains an obstacle for its use in certain situations where schistosomiasis control is envisaged and where S. madagascariensis is found. However, S. madagascariensis is a valid candidate molluscicide which may be applied in selected epidemiological settings as part of integrated schistosomiasis control measures.

Animals↗

[Poisoning by domestic vipers (Vipera berus and Vipera aspis). A retrospective study of 113 patients].

In a retrospective study, 113 bites which occurred in Switzerland within a 16-year period by either of the two indigenous adders (Vipera berus and Vipera aspis) were analyzed. 13 patients showed no signs of envenomation. Out of the other 100, 62 patients had merely minor (local edema only) and 24 moderate envenomation (vomiting, diarrhea, cramps, hypotension), while 24 had severe envenomation (shock and angioneurotic edema of the tongue and lips). No fatalities were recorded. In residents of the endemic area the bites occurred accidentally in 86% of the cases, while tourists were bitten after manipulating the snake in 42%. Specific antivenin was given to 49 of 95 hospitalized patients. In cases of severe envenomation (n = 14) a reduction of the median duration of hospitalization from 10 days in patients without antivenin therapy (n = 4) to 5 days in patients with antivenin therapy (n = 10) was obtained. In cases of moderate (n = 21) or minor envenomation (n = 49), antivenin therapy did not influence the hospital stay of 4 and 2 days respectively. In the 11 patients with bites not followed by envenomation the antivenin treatment increased the duration of hospitalization from 1 day (in 6 patients without antivenin) to 2 days (in 5 patients with antivenin). Side effects of the antivenin treatment, such as urticaria, angioneurotic edema, respiratory distress, fever and lymphadenopathy were noted in 4 out of 49 patients.

Adolescent↗

Studies on the ecology of Bulinus globosus, the intermediate host of Schistosoma haematobium in the Ifakara area, Tanzania.

During a period of 2 years, the ecology of Bulinus globosus was studied in 8 habitats in two streams near Ifakara, SE-Tanzania. The relative Bulinus densities were followed monthly. Two different methods for estimating snail densities (man/time vs. palmleaf traps) gave comparable results. Bulinus densities were constantly low throughout the year in the stream, but they showed distinct seasonal fluctuations in adjacent pools, with a density-peak at the end of the small rainy season. B. globosus, identified by starch gel electrophoresis, was found to be the only intermediate host for urinary schistosomiasis in the investigated streams. A correlation of the Bulinus densities with several abiotic and biotic factors revealed that pH, temperature and conductivity had little effect on the Bulinus population, as they oscillated within the tolerated limits. No correlation of the distribution of B. globosus and other snail species was found. Rainfall patterns have a distinct influence on snail densities. They determine the duration of desiccation and affect the snails by fluctuations of the water level and by the fast increase of water velocity after heavy rains. B. globosus shows a clear predilection for the sedge Cyperus exaltatus as support for oviposition. It is also preferred as food and/or food-support. During the dry season, oviposition of B. globosus is concentrated in clearly defined sites ("breeding pockets"), which, due to the lowering of the water level, become isolated from the stream or retain only a small connection to it. These sites form important reservoirs of B. globosus, from where the snails are spread when the sites are flooded during the subsequent rainy season. The significance of these observations for control measures is discussed.

Animals↗

[Diarrhea caused by parasites].

The role of parasites as etiologic agents in diarrhea is emphasized. In countries of western Europe, Entamoeba histolytica and Giardia lamblia are the most prevalent species, although some other 20 protozoans and helminths may lead to diarrheic disturbances. Parasitology, pathogenesis, clinical signs, diagnosis and therapy are briefly outlined. The need for competence on the part of the personnel responsible for laboratory diagnosis is emphasized; also, newly developed immunodiagnostic methods may render appreciable services in doubtful cases. Adequate therapy yields successful results in over 90% of patients.

Amebiasis↗

[Swiss cooperation in the development of public health in Tanzania].

With the financial support of the Basle Foundation for Aid to Developing Countries and in close collaboration with the St. Francis hospital, the Swiss Tropical Institute has set up and looked after a teaching centre at Ifakara, Tanzania, for the training of African medical, paramedical and auxiliary personnel. In the course of seventeen years, 770 young Africans have undergone training here. The centre has now been handed over in its final form as a Medical Assistants Training Centre to the Tanzanian Government, which has assumed full responsibility for its further direction and maintenance. The results obtained and the experience gained are discussed, as is the relationship of the centre to the public health policy of the Tanzanian Government. The writer considers that the whole undertaking has been of great mutual benefit and is looking forward to further collaboration between the Swiss Tropical Institute. Based on the Field Laboratory Ifakara, this will be mainly in applied epidemiological research, e.g. on schistosomiasis in and around Ifakara.

Allied Health Personnel↗