Species Comparison of the Role of p38 MAP Kinase in the Female Reproductive System

The p38 mitogen-activated protein kinases (MAPKs) are members of discrete signal transduction pathways that have significant regulatory roles in a variety of biological processes, depending on the cell, tissue and organ type. p38 MAPKs are involved in inflammation, cell growth and differentiation and cell cycle. In the female reproductive system, p38 MAPKs are known to regulate various aspects of the reproductive process such as mammalian estrous and menstrual cycles as well as early pregnancy and parturition. p38 MAPKs have also been implicated in alterations and pathologies observed in the female reproductive system. Therefore, pharmacologic modulation of p38 MAPKs, and inter-connected signaling pathways (e.g., estrogen receptor signaling, c-fos, c-jun), may influence reproductive physiology and function. This article provides a critical, comparative review of available data on the roles of p38 MAPKs in the mammalian female reproductive system and in reproductive pathophysiology in humans and preclinical species. We first introduce fundamental differences and similarities of the mammalian female reproductive system that should be considered by toxicologists and toxicologic pathologists when assessing the effects of new pharmacologic agents on the female reproductive system. We then explore in detail the known roles for p38 MAPKs and related molecules in female reproduction. This foundation is then extended to pathological conditions in which p38 MAPKs are thought to play an integral role.     

The effect of physiological age of potato tubers on female production of potato cyst nematodes (Globodera pallida Pa 2/3)

Fourteen cultivars generally regarded as uniformly susceptible toGlobodera pallida Pa 2/3 were assessed in plastic closed containers for degree of susceptibility and also for root and sprouting characteristics. The material was assessed by scoring degree of sprouting before planting and number of cysts and root growth at the end of experiment at intervals from the time of initial dormancy break through to prolific sprouting. Using covariate analyses, it was found that the degree of root development, particularly in the earlier assessments, significantly influenced the degree of cyst development and so the perceived levels of susceptibility/resistance. Having taken account of root growth characters, significant differences between the cultivars with regard to nematode multiplication were still evident. The implications of the results are discussed in relation to potato breeding and nematological studies.     

Fungicidal activity of the synthetic putrescine analogue, (E)-l,4-diaminobut-2-ene,and derivatives

The putrescine analogue. (E)-1,4-diaminobut-2-ene (E-BED), synthesized as the dihydrochloride salt, controlled five economically important crop pathogens, Erysiphe qraminis DC f.sp. hordei Marchal. Uromyces viciae-fabae (Pers.) Schroet, Botrytis fabae Sardina, Podosphaera leucotricha (Ell. & Ev.) Salm. and Phytophthora infestans (Mont) De Bary. The Z-isomer. Z-BED. was also fungicidal, although less so than E-BED. Post-inoculation treatment with E-BED gave greater control of powdery mildew infection on barley and rust and chocolate spot on broad bean than did pre-inoculation application. It was also effective in vitro against Botrytis cinerea Pers. ex Fr., Pyricularia oxyzae Br. & Cav. and Pyrenophora avenae Ito & Karibay. When P. avenae was grown in the presence of E-BED dihydrochloride at 81·5 mg litre^?1, growth was reduced by 58% and there were significant reductions in soluble ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activity. These changes were accompanied by a sevenfold increase in putrescine concentration, a 60% increase in spermine concentration and a 32% reduction in spermidine concentration within the fungal tissue.     

Modeling root absorption and translocation of 5-substituted analogs of the imidazolinone herbicide,imazapyr

Quantitative structure-activity relationships (QSAR) were developed between the physicochemical parameters of the 5-substituent of a series of analogs of the imidazolinone herbicide, imazapyr, and root absorption, translocation, inhibition of acetohydroxyacid synthase (AHAS), and herbicidal activity of the analogs. An optimum substituent lipophilicity (π = 1.85–2–3) for root absorption was identified for corn (Zea mays L.) and sunflower (Helianthus annuus L.). Translocation from roots to shoots was greatest for those analogs having either highly nonpolar or highly polar 5-substituents, indicating that both symplastic and apopiastic mechanisms may be functioning. In addition, translocation from roots was positively correlated with electron-withdrawing parameters of the 5-substituent, and a possible mechanism governing this relationship is discussed. Modeling in vitro AHAS inhibition was not successful, but models were developed for herbicidal activity as measured in an Arabidopsis thaliana (L.) Hevnh. bioassay. The whole-plant models described an optimum substituent lipophilicity (π = 0 71) which probably reflected the influence of this parameter on the component processes of absorption and translocation. Whole-plant activity was also greater for analogs having electron-donating 5-substituents; this result suggests that electron donation may be important for metabolism, or more likely, for AHAS inhibition.     

Anesthetic potency of sevoflurane with and without nitrous oxide in mechanically ventilated Dumeril monitors

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of sevoflurane and assess the sevoflurane-sparing effect of coadministration of nitrous oxide in mechanically ventilated Dumeril monitors (Varanus dumerili). DESIGN: Prospective crossover study. ANIMALS: 10 healthy adult Dumeril monitors. PROCEDURE: Anesthesia was induced with sevoflurane in 100% oxygen or sevoflurane in 66% nitrous oxide (N2O) with 34% oxygen, delivered through a face mask. Monitors were endotracheally intubated, and end-tidal and inspired isoflurane concentrations were measured continuously; MAC was determined by use of a standard bracketing technique. An electrical stimulus (50 Hz, 50 V) was delivered to the ventral aspect of the tail as the supramaximal stimulus. A blood sample for blood gas analyses was collected from the ventral coccygeal vessels at the beginning and end of the anesthetic period. An interval of at least 7 days was allowed to elapse between treatments. RESULTS: The MAC +/- SDs of sevoflurane in oxygen and with N2O were 2.51 +/- 0.46% and 1.83 +/- 0.33%, respectively. There was a significant difference between the 2 treatments, and the mean MAC-reducing effect of N2O was 26.4 +/- 11.4%. Assuming simple linear additivity of sevoflurane and N2O, the MAC for N2O was estimated to be 244%. No significant differences in blood gas values--with the predictable exception of oxygen pressure--were detected between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of sevoflurane in Dumeril monitors is similar to that reported for other species. The addition of N2O significantly decreased the MAC of sevoflurane in this species.     

Investigation of the potential heritability of persistent right aortic arch in Greyhounds

In 2 successive matings of the same dam and sire in a Greyhound kennel, 1 of 6 puppies and 2 of 6 puppies were born with persistent right aortic arch (PRAA) in the first and second litters, respectively. Many congenital heart defects in dogs are believed to be heritable; however, proof of this has been difficult to obtain. Genetic predisposition to PRAA has been reported in German Shepherd Dogs and Irish Setters. The occurrence of PRAA in related Greyhounds within a kennel suggested a genetic predisposition to PRAA in a breed with which it has not been associated previously. Although the number of matings available for analysis was insufficient to conclusively prove a genetic basis for these observations, the occurrence of PRAA in puppies arising from successive matings of the same dam and sire strongly suggests that some lines of dogs of various breeds may be genetically predisposed to PRAA.     

Herbicide safety relative to common targets in plants and mammals

Most modern herbicides have low mammalian toxicity. One of the reasons for this safety is that the target site for the herbicides is not often present in mammals. There are approximately 20 mechanisms of action that have been elucidated for herbicides. Of these, some do share common target sites with mammals. The mechanisms include formation of free radicals, protoporphyrinogen oxidase (PROTOX), glutamine synthetase (GS) and 4-hydroxyphenylpyruvate dioxygenase (HPPD). PROTOX, HPPD and GS inhibitors have been shown to inhibit these enzymes in both plants and mammals and there are measurable effects in mammalian systems. However, the consequences of inhibiting a common target site in plants can be quite different than in animals. What may be a lethal event in plants, eg inhibition of HPPD, can have a beneficial effect in mammals, eg treatment for tyrosinemia type I. These chemicals also have low mammalian toxicity due to rapid metabolism and/or excretion of the herbicide from mammalian systems.