Showing papers on "Animal mortality published in 1992"

Effects of Verapamil on the Acute Toxicity of Doxorubicin In Vivo

Abstract: Background Studies indicating that verapamil substantially enhances doxorubicin levels in certain drug-resistant tumor cells have led to the use of verapamil in combination with doxorubicin in animal and clinical studies of multidrug-resistant tumors. These studies have shown this drug combination to be associated with severe toxic effects. It is important to determine whether verapamil modulates the dose-limiting and potentially lethal cardiotoxicity of doxorubicin and to elucidate possible mechanisms. Purpose The aims of this study were to evaluate the in vivo effects of verapamil on (a) doxorubicin-stimulated cardiac lipid peroxidation and cardiac damage, (b) doxorubicin-induced animal mortality, and (c) biodistribution of doxorubicin to the heart. Methods Male (BALB/c x DBA/2)F1 mice were treated with a high dose of doxorubicin (15 mg/kg, injected intraperitoneally), verapamil (25 mg/kg, injected intraperitoneally), or combinations of the two. Lipid peroxidation was determined using the 2-thiobarbituric acid assay for malonaldehyde. Light microscopy was used for histopathologic examination of cardiac tissue. A fluorometric assay procedure was employed to determine doxorubicin levels in the heart. Results Verapamil was an effective inhibitor of peroxidative damage to myocardial lipids following a high dose of doxorubicin (15 mg/kg, injected intraperitoneally). However, mice treated with verapamil and doxorubicin had a lower survival rate and a higher initial peak concentration of doxorubicin in the heart than those treated with doxorubicin alone. They also demonstrated a higher incidence and severity of degenerative changes in cardiac tissue. Conclusions Our findings suggest that verapamil effectively inhibits doxorubicin-mediated lipid peroxidation in vivo but that cardiac lipid peroxidation is not the major limiting mechanism underlying doxorubicin-induced toxicity. A possible explanation for the excess mortality and cardiac injury in mice treated with verapamil plus doxorubicin is that verapamil alters the pharmacokinetics of doxorubicin. Implications Further studies are necessary for development of safer protocols and/or drug combinations to treat multidrug-resistant tumors. We are currently studying treatment of tumor-bearing animals with a cumulative dosage regimen of doxorubicin in the presence and absence of verapamil.

Correlation between increased susceptibility to primary Toxoplasma gondii infection and depressed production of gamma interferon in pregnant mice.

Abstract: To explore a possible mechanism of pregnancy-associated suppression of T cell-mediated immunity to Toxoplasma gondii, acquired resistance and gamma interferone (IFN-gamma) production in pregnant mice were compared with those in virgin mice after infection with the S-273 strain of this protozoan parasite. The 50% lethal dose of this strain was less than 200 tachyzoites for pregnant mice and 2,800 organisms for virgin controls. Toxoplasma-induced production of both IFN-alpha and IFN-gamma in the bloodstream of pregnant mice was significantly depressed as compared with that in virgin controls. The administration of recombinant murine IFN-gamma (rMuIFN-gamma) resulted in a significant decrease of mortality and parasitic growth in the organs of pregnant mice infected with a lethal dose of S-273 strain tachyzoites. Thus, the impairment of T cell-mediated immune responses was evident in pregnant mice from the impaired IFN-gamma-generating capacity and poor survival rate after primary infection with Toxoplasma. When mice with chronic Toxoplasma infection were injected with specific antigen, the resultant production of IFN-gamma was also significantly suppressed during pregnancy. However, there was no direct correlation between the serum levels of IFN-gamma and susceptibility to reinfection, since the mortality rate of chronically infected pregnant mice after the challenge with the high virulent RH strain was not significantly higher than that of virgin controls.

Evaluation of the effects of low molecular weight heparin on inflammation and collagen deposition in chronic coxsackievirus B3-induced myocarditis in A/J mice.

Abstract: Coxsackievirus, Group B, type 3 (CVB3) infection of A/J male mice induces chronic myocarditis with increased interstitial fibrosis and collagen deposition. Heparin, a naturally occurring sulfated glycosaminoglycan, has both anti-inflammatory and antifibrotic activities besides its well-known anticoagulant activity. This study determined whether heparin treatment could decrease either cardiac inflammation or fibrosis in chronic CVB3-induced myocarditis. Control mice were either untreated or treated with heparin (4 micrograms/g body weight, subcutaneously 5 times weekly) beginning 2 days before infection of other groups. Additional groups received either virus only (1 x 10(4) plaque-forming units [PFU]), virus followed by heparin beginning 14 days after CVB3 inoculation, or virus and heparin beginning 2 days before CVB3 inoculation. Animals were sacrificed 14, 28, and 58 days after infection. Heparin treatment begun either before or after virus inoculation reduced animal mortality by approximately 20%. Heparin did not alter virus infection or replication in the heart. Histologically, only animals treated with heparin before virus inoculation showed reduced myocardial inflammation, and only at day 58. However, heparin treatment begun either before or after virus infection significantly decreased collagen deposition in the heart (fibrosis).

Indigenous integrated farming systems in the Sahel

Abstract: This paper presents the results of a study examining the development of mixed farming systems in the Sahelian region of West Africa. The study was part of a program of research into the future directions of livestock production, agricultural development, and resource management in sub-Saharan Africa. Although it is widely recognized that crop and livestock production in the Sahelian countries is in crisis, the full implications for human welfare, the sustainability of farming systems, and environmental degradation are inadequately appreciated. The population explosion in recent decades is at the root of the crisis, but it is exacerbated by low rainfall, droughts, and infertile fragile soils. The process is characterized by the breakdown of pastoral systems, settlement, and the rapid adoption of integrated crop/livestock systems by traditional crop farmers and settled pastoralists. This study describes the evolution of integrated crop and livestock systems and the underlying causal factors. Particular attention is given to the allocation of resources, especially land and labor, among different crop and animal production activities. The factors that determine the adoption of animal traction, the use of manure and crop residues in farming systems, and the pattern of income generation in households are analyzed and discussed. The study concludes that present farming systems are unsustainable in the long term. Appropriate strategies are recommended.

Interaction of protein and zinc malnutrition with the murine response to infection.

Abstract: Malnutrition increases the host's susceptibility to infection. However, the mechanisms are not well understood. This study examined the interaction of protein and zinc underfeeding in mice before challenge with an intracellular pathogen, Salmonella typhimurium. C3H/HeN mice (n = 68) were weighted and placed on one of four diets: 20% ovalbumin with adequate zinc (20% NL), 20% ovalbumin without zinc (20% LO), 1% ovalbumin with zinc (1% NL), and 1% ovalbumin without zinc (1% LO). At the end of 6 weeks they were again weighed and then challenged with 10(4) S. typhimurium intraperitoneally. Mortality was recorded over the next 2 weeks. Although weight loss was markedly affected by protein malnutrition (two-way analysis of variance: p = .0001), there was no independent effect by zinc (p = .3459). Similarly, protein malnutrition alone affected mortality rates (chi 2: p = .0001), whereas zinc had no independent effect (p = .7166). However, both protein and zinc underfeeding shortened the length of survival (Mann-Whitney U test: p less than .001). We conclude that protein malnutrition is the dominant factor influencing weight loss and mortality in this model. However, zinc malnutrition does shorten the length of survival and may contribute to the global immunosuppression noted in malnourished subjects.

A Note on Historical Mortality in a Northern Bison Population

Abstract: Mortality of bison in the area of what is now Wood Buffalo National Park was recorded in records of Fort Chipewyan for the years 1821, 1823, and 1831. There is oral tradition in the Fort Smith area that many bison died in the Slave River lowlands during one summer later in the 19th century. The records of sudden death among bison during the summer resemble features of anthrax mortality that occurred among bison in the same general area between 1962 and 1978. This suggests that anthrax may have a much longer history in the region than recognized previously. Key words: northern bison, disease, ethnohistory, anthrax