The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

Clinical findings and treatment in 63 cows with haemorrhagic bowel syndrome.

The clinical, haematological and biochemical findings, treatment and outcome of 63 cows with haemorrhagic bowel syndrome are described. The general condition and demeanor were moderately to severely abnormal in all the cows. Signs of colic occurred in 27 cows, decreased rectal temperature in 46 and tachycardia in 44. With the exception of one cow, intestinal motility was decreased or absent. Transrectal palpation revealed dilatation of the rumen in 47 cows and dilatation of the small intestine in 18. Faecal output was markedly reduced or absent, and the faeces were dark brown to black and contained blood. Nine cows were euthanized immediately after physical examination. Conservative medical therapy was instituted in two cows; however, both were euthanized a few days later because of deterioration in condition. Exploratory right flank laparotomy was carried out in 52 cows. Of these, 22 were euthanized intraoperatively because of severe lesions. In 27 cows, intestinal massage to reduce the size of blood clots was carried out; 11 were euthanized several days postoperatively because of deterioration in condition. In three other cows, intestinal resection was carried out and all survived. Of the 63 cows, 19 (30.2%) survived and were healthy at the time of discharge from the clinic.

The effects of male age on sperm DNA damage in healthy non-smokers.

BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.

Promising community-level indicators for evaluating cardiovascular health-promotion programs.

Rigorous evaluation of community-based programs can be costly, particularly when a representative sample of all members of the community are surveyed in order to assess the impact of a program on individual health behavior. Community-level indicators (CLIs), which are based on observations of aspects of the community other than those associated with individuals, may serve to supplement individual-level measures in the evaluation of community-based programs or in some cases provide a lower-cost alternative to individual-level measures. Because they are often based on observations of the community environment, CLIs also provide a way of measuring environmental changes--often an intermediate goal of community-based programs. The Centers for Disease Control and Prevention convened a panel of experts knowledgeable about community-based program evaluation and cardiovascular disease (CVD) prevention to develop a list of CLIs, and rate their feasibility, reliability and validity. The indicators developed by the panel covered tobacco use, physical activity, diet and a fourth group that were considered 'cross-cutting' because they related to all three behaviors. The indicators were subdivided into policy and regulation, information, environmental change, and behavioral outcome. For example, policy and regulation indicators included laws and ordinances on tobacco use, policies on physical education, and guidelines for menu and food preparation. These indicators provide a good starting point for communities interested in tracking CVD-related outcomes at the community level.

[Our therapy concept in nonresectable liver metastases]. / Unser Therapiekonzept bei nichtresezierbaren Lebermetastasen.

Cytotoxic chemotherapy was performed in a total of 18 patients (12 men, 6 women): 5 patients with colonic carcinoma and 1 patient with unknown primary lesion received 5 x 1000 mg 5-Fluorouracil (5-FU) at 4 week interval. The 5 following patients primarily suffering from colonic carcinoma were treated with 0.5 mg/kg BW FUDR continuously at 2 week interval. 5 further patients with colonic carcinoma sequential received Mitomycin C (8 mg/m2) and 4 x 1000 mg 5-FU. 2 patients with breast cancer were treated with 500 mg/m2 Cyclophosphamide, the same amount of 5-FU and 40 mg/m2 Methotrexate every 4 weeks. Chemotherapy was well tolerated by all patients. A clinically significant response, however, was seen in only 2 patients with breast cancer. In 8 patients a liver transplantat was performed, which was followed in 3 cases by ultra-high dose Cyclosphosphamide, lethal total body irradiation and autologous bone marrow transplantation. 1 further patient received polychemotherapy. At the time of this analysis only 3 patients were still alive at 61, 30 and 26 months with only 1 perioperative death. All 3 had meanwhile developed recurrent or metastatic disease. Because of these sobering results, liver transplantation for the treatment of non-resectable liver metastases has been abandoned, and regional chemotherapy is now only applied in patients with liver metastases from breast cancer and after resection of metastases in an adjuvant setting.