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Insects as novel foods are gaining popularity in Europe. Regulation (EU) 2015/2283 laid the framework for the application process to market food insects in member states, but potential hazards are still being evaluated. The aim of this study was to investigate samples of edible insect species for the presence of antimicrobial-resistant and Shiga toxin-producing Escherichia coli (STEC). Twenty-one E. coli isolates, recovered from samples of five different edible insect species, were subjected to antimicrobial susceptibility testing, PCR-based phylotyping, and macrorestriction analysis. The presence of genes associated with antimicrobial resistance or virulence, including stx1, stx2, and eae, was investigated by PCR. All isolates were subjected to genome sequencing, multilocus sequence typing, and serotype prediction. The isolates belonged either to phylogenetic group A, comprising mostly commensal E. coli, or group B1. One O178:H7 isolate, recovered from a Zophobas atratus sample, was identified as a STEC. A single isolate was resistant to tetracyclines and carried the tet(B) gene. Overall, this study shows that STEC can be present in edible insects, representing a potential health hazard. In contrast, the low resistance rate among the isolates indicates a low risk for the transmission of antimicrobial-resistant E. coli to consumers.

To date, only a few studies on the azithromycin (AZM) pharmacokinetics in ornamental birds have been published. In the current study AZM concentrations in domestic pigeon (Columba livia domestica) plasma samples were analyzed using a validated ultra-high performance liquid chromatography tandem mass spectrometry method. The aim of the current study was to carry out an analysis of the pharmacokinetics and pharmacodynamics after administration of a single oral dose of a sustained-release AZM formulation and to conduct a simulation of treatment based on selected minimal inhibitory values. The study was performed with 12 healthy adult pigeons, both sexes. The pigeons tolerated AZM very well and no adverse effects were observed in any animal during the study. Based on the observed characteristics of the pharmacokinetics/ /pharmacodynamics profiles of AZM in pigeons, it should be noted that 35 mg/kg per os as a single starting dose and 25 mg/kg every 24 h are recommended for treatment of both suscep- tible and less susceptible pathogens.

From the regulatory point of view a strong link between an animal model and human pharmacodynamics of biological drugs is very important to qualify the model as "relevant". Consistent changes in cell population between human physiology and animal model gain value of this model which then can be pharmacodynamically "relevant" from the regulatory point of view. Consequently, the aim of this study was to determine how similar to human observations is the effect of selected biological drugs on blood cells in a pig model. The study was to carry out a comparative analysis of the variability of selected biochemical and hematological parameters of the blood after administration of five different human therapeutic monoclonal antibodies (mAbs) after a single subcutaneous (SC) dose in breeding pigs. The tested drugs were siltuximab (Syl- vant®), omalizumab (Xolair®), infliximab (Inflectra®), pembrolizumab (Keytruda®), and vedoli- zumab (Entyvio®) given in a single 1 mg/kg SC injection. Each of the tested drugs exerted a sig- nificant effect on at least two of the tested parameters three weeks after the administration. Siltuximab significantly influenced 9 of the analyzed parameters. Vedolizumab significantly influenced 8 of the analyzed parameters. Infliximab had the lowest impact of all the tested drugs, as it significantly influenced only two of the analyzed parameters. The study has proved that the impact of mAbs on the analyzed parameters can be significantly extended over time. This requires the monitoring of hematological parameters in the pig model even many weeks after administration of a drug in a relatively small dose.

The aim of this study was to determine to what extent the ions present in hard water (125 mg/L of MgCl2 and 500 mg/L of CaCl2) may intensify the feed-induced decrease in oxytetracycline (OTC) absorption rate in broiler chickens after single oral administration at a dose of 15 mg/kg. Drug concentrations in plasma were determined by liquid chromatography-tandem mass spectrometry and combined, compartmental and non-compartmental approach was used to assess OTC pharmacokinetics. The administration of feed decreased the absolute bioavailability (F) of OTC from 12.70%±4.01 to 6.40%±1.08, and this effect was more pronounced after the combined administration of OTC with feed and hard water (5.31%±0.90). A decrease in the area under the concentration- time curve (AUC0-t), (from 10.18±3.24 μg·h/ml in control to 5.13 μg·h/ml±1.26 for feed and 4.26 μg·h/ml±1.10 for feed and hard water) and the maximum plasma concentration of OTC (Cmax) (from 1.22±0.18 μg/ml in control, to 1.01 μg/ml ±0.10 for hard water, 0.68 μg/ml±0.10 for feed and 0.61 μg/ml±0.10 for feed and hard water) was observed. The results of this study indicate that feed strongly decreases F, AUC0-t and Cmax of orally administered OTC. The ions present in hard water increase this inhibitory effect, which suggests that, therapy with OTC may require taking into account local water quality and dose modification, particularly when dealing with outbreaks caused by less sensitive microorganisms.

Chronic pancreatitis (CP) is a disease leading to irreversible pancreas dysfunction. One of the main symptoms is pain. Many patients require pharmacological therapy which should be started with paracetamol or, in selected groups of patients, ketoprofen. If the effect of ketoprofen is irrelevant, patients receive tramadol. The aim of this study is the evaluation of ketoprofen and tramadol pharmacokinetics (PK) in CP patients.36 patients were divided into two groups: I - receiving ketoprofen (n=18; mean [SD] age, 48.61 [13.32] years; weight, 73.28 [20.48] kg), II - receiving tramadol (n=18; mean [SD] age, 46.78 [10.28] years; weight, 74.22 [14.04] kg, and BMI (Body Mass Index), 24.61 [4.51] kg/m2). The plasma concentrations of ketoprofen and tramadol with its active metabolite M1 (0-desmethyltramadol) were measured with the validated high-performance liquid chromatography method.The main PK parameters for ketoprofen were as follows: Cmax (maximum plasma concentration), 3.41 [2.32] mg/L; AUC0-inf (area under the plasma concentration-time curve from time zero to infinity), 10.45 [5.57] mg⋅h/L; tmax (time to first occurrence of Cmax), 1.94 [1.25] h; Cl (clearance), 0.199 [0.165] L/kg·h, and Vd/kg (volume of distribution per kilogram of body weight), 0.71 [0.58] L/kg. The main PK parameters for TRM and M1 were as follows: Cmax, 226.4 [80.5] and 55.6 [23] ng/mL; AUC0-inf, 1903.3 [874.8] and 790.4 [512.4] ng⋅h/mL; tmax, 1.78 [0.73] and 2.67 [1.19] h, respectively.Chronic pancreatitis led to a decrease in the total amount of absorbed ketoprofen. Consequently, the analgesic effect of the drug may be weaker. Cmax of tramadol for most CP patients was within the therapeutic range associated with its analgesic activity. M1/TRM ratios for Cmax and AUC were unchanged.

The aim of the research was an examination of potential impact of milk yield on the intercompartmental clearance - distribution clearance as well as determination of the variability of obtained pharmacokinetic parameters by the population approach using a two-compartmental structural model. Blood perfusion has a considerable impact on physiology of the udder and kinetics of drugs that are distributed in this organ. The research was performed on healthy Holstein- Friesian and Polish Black-White cows at the age of 4-10 years. Determination of antibiotics (ampicillin, amoxicillin, cefoperazone, penicillin G prokaine, cloxacillin, cefacetril) concentration was carried out after their every intramammary administration to one quarter of the udder. A population pharmacokinetic model was created to fit milk concentration data. General milk yield of a single cow was used as a variable. A population analysis was conducted using non-linear mixed-effect modeling. The impact of milk productivity was set solely by reference to intercompartmental clearance only in case of penicillin G, cloxacillin and ampicillin. It, has been found that milk yield, depending on a drug, influenced the distribution clearance of the drug to varying degrees. It means indirectly that increased perfusion of the udder has a different impact on drug distribution from the udder to the bloodstream.

It is well known that during the suckling period pancreatic secretion is low. The aim of the study was to investigate the effects of dietary supplementation with pancreatic-like enzymes of microbial origin (PLEM) and SiO2, as an antibacterial factor, on the performance of piglets fed creep feed during weaning and thereafter. The experiment was performed on piglets from 30 litters. The piglets were divided into 5 groups (n = 63–66) and weaned at the age of 28 d old. The control group received standard creep feed (Days 7–28), and groups P1 and P2 and groups PA1 and PA2 received creep feed with SiO2supplemented with protease (P1 and P2) or with protease+amylase (PA1 and PA2) during Days 7–13 (P1 and PA1) or Days 14–20 (P2 and PA2) before weaning. Dietary supplementation with PLEM and SiO2led to a significant (P < 0.05) increase in ADG in the treated piglets compared to the control with the best results obtained in group P2. To summarize, creep feed supplemented with PLEM improves productivity parameters of piglets under standard rearing conditions.

The reduced value of resistance (R) of milk (167Ω) or increased conductivity (EC)6.0 mS/cm indicate the growing number of ions in milk during the initial phase of mastitis. The aim of this study is to demonstrate a linear (verified by a validation procedure) dependency between R and mean daily yield (MDY), which could be used for current monitoring and forecasting of milk yield in dairy cow herds. Although the topic has frequently been examined, a validated model for prediction of MDY based on R has still not been presented.Data from 118 dairy cows were analyzed in the study. The validation of model dependency R↔MDY was performed by the live-one-out method (LOO).The minimum geometrical/arithmetical mean of R milk was observed during the 1st month of lactation and was 53.40/254.86 Ω. However, the maximum geometrical/arithmetical mean of R milk was observed during the 7th month of lactation and has 189.62/574.51 Ω. The final model was described by the curve equation MDY = -04461 × R% + 51.58 where R% - percentage share of cows in a herd whose R oscillated within the limits 49.38-154.32 Ω.Complete predictivity of the model within the above mentioned limits ("prognostic range") was confirmed by the results of validation of the model. The developed model enables the efficiency of a herd at specified percentage share of cows of defined milk R value to be determined.

It is still a challenge to predict a compound's reactivity from its ground-state electronic nature although Bader-type topological analyses of the electron density (ED) and electron localizability indicator (ELI) give detailed and useful information on electron concentration and electron-pair localization, respectively. Both ED and ELI can be obtained from theoretical calculations as well as high-resolution X-ray diffraction experiments. Besides ED and ELI descriptors, the delocalization index is used here; it is likewise derived from theoretical calculations as well as from experimental X-ray results, but in the latter case, demonstrated here for the first time. We investigate α,β-unsaturated carbonyl and hydrazone compounds because resonance exhibited by these compounds in the electronic ground-state determines their reactive behavior. The degree of resonance as well as the reactivity contrast are quantified with the electronic descriptors. Moreover, competitive mesomeric substituent effects are studied using the two biologically important compounds acrolein and acrylamide. The reactivity differences predicted from the analyses are in line with the known reactivity of these compounds in organic synthesis. Hence, the capability of the ED and ELI for rationalizing and predicting different and competing substituent effects with respect to reactivity is demonstrated.

N, N-Dimethylhydrazonesof propenal- and 2-methyl-propenal and their derivativesand homologues (vinylogous aza-enamines) were allowed to react with N, N-dimethylformiminium chloridein moisture-free dimethylformamide to yield singly, doubly, andeven triply aminomethylated products. They can be easily separatedand characterized as crystalline hydrochlorides. The reaction takesplace at the ω-position of the π-system. Thisis a consequence of the conjugative interaction of the electron-donating aminohydrazonegroup with the double bond system in analogy to the enamines. Theformation of dialkylhydrazones from unsaturated aldehydes thus causesthe umpolung of the formerly electrophilic d 3 -buildingblocks into a nucleophile. Depending on the reaction conditionsand confirmed by crystal structures and 2D NMR experiments, controlcan be exerted over the degree of substitution: Up to trisubstitutedproducts were obtained for the 2-methylpropenal derivative. Thehydrochlorides can be easily deprotonated to yield the free aminohydrazonebases. The back-conversion of the aminohydrazones into the correspondingamino aldehydes is possible under acidic conditions.

Honey has been considered a relatively safe foodstuff due to its compositional properties, with infant botulism caused by Clostridium botulinum being the most prominent health risk associated with it. Our review is focused on the honey microflora along the food chain and evaluates the pathogenic potential of those microorganisms found in honey. This product may contain a great variety of bacteria and, particularly, fungi that eventually entered the food chain at an early stage (e.g., via pollen). For many of these microorganisms, opportunistic infections in humans have been recorded (e.g., infections by Staphylococcus spp., Citrobacter spp., Escherichia coli, Hafnia alvei, Aspergillus spp., Fusarium spp., Trichoderma spp., Chaetomium spp.), although direct infections via honey were not registered.

Mice with null mutations for metallothionein genes MT-1 and MT-2 were used to study the role that metallothionein plays in protecting cellular targets in vivo from oxidative stress. Wild-type (MT(+/+)) and MT-null (MT(-/-)) mice were treated with either saline or zinc and exposed to two types of oxidative stress: gamma-irradiation or 2-nitropropane. There was no alteration in the antioxidant defense system (superoxide dismutase, catalase, or glutathione peroxidase and glutathione levels) to compensate for the lack of the metallothionein in the MT(-/-) mice. The amount of oxidative damage to liver DNA, lipids, and proteins were similar for the MT(-/-) and MT(+/+) mice even though the levels of metallothionein in the livers of the saline- or zinc-pretreated MT(+/+) mice were 5- to 100-fold greater than found in the MT(-/-) mice. To determine if metallothionein can protect mice from the lethal effects of ionizing radiation, the mean survivals of MT(-/-) and MT(+/+) mice exposed to whole body gamma-irradiation were measured and found to be similar. However, the mean survival increased significantly after zinc pretreatment for both the MT(-/-) and MT(+/+) mice. These results demonstrate that tissue levels of metallothionein do not protect mice in vivo against oxidative stress.

N-Methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, is responsible for the removal of a wide variety of alkylated base lesions in DNA, e.g., N-alkylpurines and cyclic ethenoadducts of adenine, guanine, and cytosine. These lesions, some of which are mutagenic and toxic, are generated endogenously or by genotoxic agents such as N-alkylnitrosamines and vinyl chloride. Wild-type mouse MPG, expressed from recombinant baculovirus, was purified to near homogeneity for studying its specific interaction with substrate, 1,N6-ethenoadenine- (epsilonA-) containing DNA. Electrophoretic mobility shift assays (EMSA) indicated that MPG formed a specific complex with a 50-mer epsilonA-containing duplex oligonucleotide. This complex was shown to be a transient reaction intermediate, because it could be formed only with the unreacted substrate and contained active enzyme molecules. DNA footprinting studies confirmed the specific binding of the protein to the epsilonA-containing duplex oligonucleotide; eight nucleotides on the epsilonA-containing strand and 16-17 nucleotides in the complementary strand spanning the base adduct were protected from DNase I digestion. A systematic deletion analysis of MPG was carried out in order to determine the minimally sized polypeptide capable of forming a stable substrate complex that is also suitable for characterization by NMR spectroscopy and X-ray crystallography. A truncated polypeptide (NDelta100CDelta18) lacking 100 and 18 amino acid residues from the amino and carboxyl termini, respectively, was found to be the minimal size that retained activity. The truncated and wild-type enzymes have similar kinetic properties. Moreover, both EMSA and DNase I footprinting studies indicated identical pattern of specific binding by the truncated and full-length polypeptides. Removal of five and nine additional residues from the amino- and carboxyl-termini of this polypeptide, respectively, resulted in a complete loss of activity. These results suggest that minimal structural change occured as a result of truncation in the NDelta100CDelta18 mutant, which may thus be suitable for elucidating the structure and mechanism of MPG.

We have designed an experiment in which it appears that we can measure the pressure, volume, temperature, and electrical conductivity of a metal simultaneously. These data aid in the modeling of conductivity and equation-of-state relations for metals that are driven to extreme states, for example in z-pinches, imploding liners, or high-power electrical fuses. Recent advances in the technique of measuring the temperature of a surface with variable spectral emissivity can produce measurement accuracy of a few percent. The experiment is arranged so the fuse material investigated is subject to one-dimensional movement only. In addition, conditions must be such that the state parameters are nearly uniform throughout the region being measured. In one such arrangement, a thin planar foil is sandwiched between two pieces of lithium fluoride and a suitably large current is passed through the foil. The initial heating is not one- dimensional due to the time required for the magnetic field to diffuse into the foil; however, for certain geometries of the foil (such as 3 cm wide and 0.008 cm thick), the conditions at the center of the foil satisfy the conditions of one-dimensionality after a few microseconds. The displacement of the foil interface with the lithium fluoride allows the computation of the density of the foil material (typically copper or aluminum). The velocity of the surface together with the known equation of state of the lithium fluoride gives the pressure at the interface and, by the one-dimensionality of the conditions, the pressure through the center of the foil. The conductivity is measured by measuring the electric field using voltage probes, with the current density inferred from a local measurement of the magnetic field at the surface of the foil. Other fuse geometries such as rods or cylindrical foils are also candidates for the experiment. Detailed two-dimensional calculations of the current and material flow have been performed and will be discussed.

To assess the ability of baseline MRI characteristics to predict the early development of clinically definite MS (CDMS) and combined CDMS/MRI outcomes in 190 patients with a positive MRI at the time of their first demyelinating event.Based on individual and sets of baseline MRI characteristics, the authors evaluated the percentage of patients meeting outcomes of CDMS and various combined CDMS/MRI outcomes by 18 months. They also optimized a cutpoint for dichotomizing each baseline MRI characteristic and evaluated these variables using logistic regression to determine which MRI characteristics best predicted CDMS by 18 months.The presence of two or more gadolinium-enhancing lesions better predicted the development of CDMS and combined CDMS/MRI outcomes by 18 months than any other individual MRI characteristic or set of MRI characteristics. Among patients with two or more gadolinium-enhancing lesions, 52% developed CDMS compared with 24% of patients with fewer than two lesions. For those meeting the criteria of Barkhof et al., 32% of patients developed CDMS compared with 16% of those not meeting these criteria. Irrespective of individual or sets of criteria, however, the majority of patients developed either CDMS or demonstrated disease activity on brain MRI by 18 months.For patients with positive MRI at the time of their initial neurologic event, both gadolinium-enhancing lesions and the Barkhof criteria are predictors for development of CDMS over a short interval. However, these results, based on a combined CDMS/MRI outcome, suggest that the majority of these patients are already in the earliest stages of MS, regardless of whether any further MRI criteria are met.

We evaluated 190 patients in the placebo group of the CHAMPS trial in order to assess factors associated with short-term clinical and brain magnetic resonance imaging (MRI) outcomes in patients with a first clinical demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and subclinical demyelination on brain MRI. The two study outcomes were 1) development of clinically definite multiple sclerosis (CDMS) and 2) development of CDMS or two or more new or enlarging brain MRI T2 lesions. The presence of gadolinium (Gd)- enhancing lesions on the baseline scan was the only MRI characteristic associated with a higher risk of both the clinical and combined outcomes (p=0.003 and

Nearly 40 years ago it was proposed that accumulation of mutations or increased levels of DNA damage might contribute to aging processes. Despite several correlative studies in this area, the answer as to whether genomic integrity contributes to aging has remained illusive. More recently it has been hypothesized that decreased mitochondrial DNA integrity plays a role in aging. To begin to test these hypotheses more directly, we are developing transgenic mouse and cell culture model systems. For example, transgenic mice overexpressing the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) have been made and have a reduced spontaneous frequency of hepatocellular carcinoma. A lifespan study using the MGMT transgenic mice is in progress in an effort to determine whether cancer impacts on the median or maximal lifespan of a species. Second, a quantitative PCR technique is being used to measure mitochondrial DNA damage in mitotic and post-mitotic cells to determine if the level of damage and/or repair is different based on mitotic status. Finally, mice deficient in metallothionein-I and -II are being used in an effort to determine if the subcellular distribution of metals impact on oxidative damage with increased age.

O6-Methylguanine-DNA methyltransferase (MGMT), a ubiquitous DNA repair protein, acts as a monomer in removing the mutagenic DNA adduct O6-alkylguanine (induced by alkylating carcinogens) via a stoichiometric reaction. The alkyl group is transferred without a cofactor to a specific cysteine acceptor residue of MGMT, Cys-145 in the case of human MGMT, containing 207 amino acid residues and thereby inactivates the protein. As a prelude to the investigation of the reaction mechanism of human MGMT by elucidation of its structure in free and substrate-bound forms via NMR spectroscopy and X-ray crystallography, two types of MGMT mutants were generated and characterized. First, systematic deletion analysis of the protein was carried out to determine the smallest size at which it is active or inactive but forms a stable complex with the substrate and so may be useful for NMR spetroscopic analysis. Deletion of more than 8 or 31 residues from the amino or carboxyl terminus, respectively, led to the loss of both activity and substrate binding. Removal of Arg-9 or Leu-176 and distal residues inactivated the protein, presumably by altering its tertiary structure. On the basis of the criteria of bacterial overexpression and solubility, the mutant MGMT with deletion of 28 residues at the carboxyl terminus should be suitable for NMR studies. In the second approach, we examined mutants at the active site (Cys-145) that retain substrate binding. Inactive C145A and C145S substitution mutants were found to form specific and stable complexes with an O6-methylguanine (m6G)-containing oligonucleotide substrate. Wild type MGMT also formed a similar complex, but only as a transient intermediate. Footprinting studies indicated a strong discriminatory effect of the base adduct on the binding of C145A to substrate DNA; 17-18 nucleotides on the m6G-containing strand and 13-14 nucleotides in the complementary strand spanning the base adduct were protected from DNase I digestion by the mutant protein. These results, as well as the identical protease sensitivity of the wild type and mutant proteins, suggest minimal structural change due to conservative mutations at the active site. Thus, the mutant proteins may be utilized for solving the structure and mechanism of human MGMT.

We initiated this study to determine whether three structurally related bifunctional alkylating agents could induce the expression of a presumptive human DNA repair gene. The gene chosen for this study is known to encode the ribosomal phosphoprotein PO, but ironically may also share functions related to DNA repair. We now show by Northern analysis that PO is induced by L-phenylalanine mustard, 4-hydroperoxycyclophosphamide and mechlorethamine, which are DNA-damaging agents commonly used as chemotherapeutic antitumor agents. In further support of its involvement in DNA repair is the finding of a 30- to 50-fold constitutive overexpression of the PO gene in human tumor cell lines that are Mer-, cells which lack O6-methylguanine methyltransferase activity, when compared to Mer+ cell lines. This constitutively elevated level of PO in Mer- cell lines, which are thus DNA repair defective for O6-alkyguanine lesions, was not observed for other genes tested, including the human ribosomal gene S17 whose mRNA steady-state levels were uniformly the same in both Mer- and Mer+ cells. Taking these data together, it appears that increased levels of PO are somehow linked to DNA repair, and increased expression of PO may compensate for the decreased O6-methylguanine DNA methyltransferase activity in Mer- cells. Furthermore, the PO gene has also been shown to be overexpressed in colorectal tumors and polyps and the sera of some systemic lupus erythematosus patients contain antibodies against PO. The titer of the anti-PO antibodies rises significantly during lupus psychosis.

A cDNA has been isolated for an adult male specific gene in Drosophila that contains the repetitive element opa . We have named this gene Dromsopa for Drosophila male specific opa containing gene. The 0.6 kb mRNA for this gene is only found in the abdominal region of adult male Drosophila and in no other tissue or at other developmental stages. The Dromsopa opa repeat codes for the usual stretch of poly(glutamine) interrupted by histidine residues. The opa repetitive element was originally found in the Drosophila Notch gene (Kidd, S. et al. (1983) Cell 34, 431–433 and Wharton, K.A. (1985) Cell 40, 55–62) and has, more recently, been found in genes under developmental or tissue specific control from yeast to humans. The gene was cloned using a genomic fragment during a chromosomal walk upstream of the AP3 gene located at chromosomal location 79CD on the left arm of the third chromosome (Kelley, M.R. et al. (1989) Mol. Cell. Biol. 9, 965–973). The Dromsopa gene has no other identity with genes currently in the databases, once the opa repeat is excluded. The possibility that the Dromsopa gene is a male specific regulatory factor is under investigation as is its precise location within the abdomen, such as in germ line tissue.

Esophageal stenosis caused by an intrinsic congenital deformity is uncommon in infants and children. The main forms of stenosis are congenital esophageal web, congenital stricture caused by tracheobronchial remnants, and congenital idiopathic muscular hypertrophy. The authors report on two patients who were successfully treated and managed after being diagnosed as having upper esophageal stenosis. One patient underwent resection of the web and primary anastomosis of the esophagus and was discharged 6 days after surgery. After 1 year, this patient has had no symptoms of dysphagia or other postoperative difficulties. The second patient underwent balloon dilatation of the esophageal stricture and was discharged on the day of surgery; however, this patient required numerous repeat dilatations.

The need for timely, accurate, and locally relevant career information has been escalating. Within the last fifteen years, computer-based systems have been developed which put occupational descriptions, labor market information, plus education, training and financial aid information into formats usable by students and adults in school and non-school settings. The proliferation of systems marketed competitively, the increasing depth and breadth of information available, plus the sophistication of the guidance aspects of systems has produced a consumer's dream, but also a major dilemma. Selection of a system for a statewide or substate unit which corresponds to the particular needs of the targeted constituency requires thorough knowledge of the prospective users' characteristics, material, and human resources available, hardware capacities, software content and hardware/software compatibility. This paper provides a context for understanding the properties of computer-based systems, their theoretical approaches and the dimensions to the problems of selection.

The effects of lactational mirex exposure on postnatal lens cation balance, lens growth and histology were examined in this study. Pregnant Long Evans rats were allowed to give birth, and litters were culled to eight individuals. Dams were intubated with 10 mg kg-1 day-1 mirex on days 1-4 postpartum. Pups were killed at 6-14 days of age, and lenses were removed, examined for opacities, weighed, and assayed for K+ and Na+ concentrations. Cataracts occurred in 71.0% of all treated litters and 58.1% of all treated individuals. Histologically, lenses from treated pups showed anterior and posterior cortical vacuoles by 8 days of age, greatly swollen lens fibers by 10 days of age, and areas of cell degeneration by 12-14 days of age. Lens K+:Na+ ratios were lower in treated groups on days 8-14 after birth, in both clear and cataractous lenses, and cataractous lenses were significantly higher in water content. Lens:eye weight ratios were not affected. The results of this study indicate that mirex-induced postnatal cataracts are due to lens degeneration subsequent to fiber cells swelling.

Prenatal exposure to mirex induces a high rate of perinatal death without obvious cause. Part I of this study (Grabowski and Payne, 1982), in which fetuses were exposed to a moderate dose of mirex and observed just prior to parturition, it was found that 14% had died recently and an additional 9% were apparently dying with serious cardiovascular symptoms. In the present study, electrocardiograms of normal (oil‐fed controls) and mirex‐exposed rats (6 mg/kg·d of insecticide on d 8 to 15 of gestation) were obtained at birth and for several days afterwards. An ECG was obtained from most individuals within 5 min of birth. Pups were then weighed and tattooed so that individuals could be followed to postnatal d 5. Data on 70 control newborns were compared with that on 131 mirex‐treated pups. In the treated group, 23% were stillborn. Of those born alive, 8% died within 6 h of birth, and another 13% within 48 h. At birth, 14% had first‐degree heart blocks, and 2% had second‐degree blocks. All of those with second‐...

A significant effect of prenatal exposure to the pesticide Mirex is a fetal edema, which is responsible for many of the toxic effects of this agent. Pregnant rats were given 6 mg/kg mirex on d 8 1/2-15 1/2, a moderate dose that does not cause maternal mortality. The blood of 18 1/2- and 20 1/2-d rat fetuses was tested to determine a possible cause of the edema. There were no significant differences between fetal and maternal plasma or between control and treated fetal plasma with respect to sodium and potassium concentrations or total osmolality. The protein concentration of plasma of treated fetuses was lower than that of controls. This effect was proportional to the degree of edema. The concentration in 20 1/2-d controls was 25.2 mg/ml, that in mildly swollen treated fetuses 18.1 mg/ml, and that in severely swollen ones 13.5 mg/ml. Polyacrylamide gel electrophoresis showed quantitative and qualitative changes in plasma of affected fetuses. The colloid osmotic pressure was also reduced fron 8.0 mm in controls and unaffected treated fetuses to 4.8 mm in swollen fetuses. Since lowered plasma protein and colloid osmotic pressure cause tissue edema in adults, they are the probably cause of mirex-induced fetal edema.

Trypan blue is a potent teratogen in vivo and in vitro in the rat. Many of the abnormalities produced by trypan blue--including swollen neural tube and pericardium, subectodermal blisters, hematomas, and generalized edema--may result from altered fluid balance in and around the embryo. The present study demonstrates relationships between changes in the fluid environment around the embryo and appearance of anomalies. Rat embryos were exposed in utero or in vitro to trypan blue during the early period of organogenesis. Both exposures resulted in defects that are typical of trypan blue treatment. Osmolality of exocoelomic fluid (ECF) was measured on gestation day 10 in vivo and day 12 in vitro, both after 48 hr of exposure to trypan blue. In both cases ECF osmolality was significantly lower than controls. This was correlated with the presence of edema-related anomalies in the embryo. On gestation day 11 in vivo, three days after maternal injection of trypan blue, ECF osmolalities were significantly higher than controls; however, there was tremendous variability in this parameter in day 11 treated embryos, and some had ECF osmolalities below the control range. Increased frequency of abnormalities was correlated with abnormal ECF osmolality, below and above the control range. Trypan blue probably exerts its teratogenic effects by disturbing the function of the visceral yolk sac. The movements of an amino acid and a monosaccharide across the visceral yolk sac were measured on gestation day 12 embryos in vitro. This aspect of yolk sac function was not altered by trypan blue exposure. Ultrastructure of the visceral yolk sac was observed after trypan blue exposure in vivo and in vitro. Endodermal cells in trypan blue-treated yolk sacs contained fewer large, electron dense lysosomes than controls. These were replaced by numerous small vacuoles, which may contain trypan blue. Trypan blue causes osmotic changes in the rat embryo in vivo and in vitro. These changes are correlated with embryonic malformations. Alterations in yolk sac ultrastructure indicate that trypan blue affects the function of this membrane.

Pregnant rats were exposed to either 0, 1.0, or 1.5 ppm ozone during either mid gestation (Days 9-12) or late gestation (Days 17-20). The dams were allowed to deliver and the early morphological and behavioral development of their pups was monitored. Both exposure regimens transiently reduced neonatal growth rates. The late gestation exposure regimen produced retardations in early reflex development and in open field behavior. Finally, several males from this exposure regimen remained permanently stunted in growth.

Treatment of chick embryos early in development with the teratogen, trypan blue, results in a high incidence of rumplessness at later developmental stages. Experiments were conducted to discover the causative events between dye administration and rumplessness. Initially, 167 two-day embryos were treated by injection of 0.02 ml 0.1% trypan blue (in saline) into the yolk sac. Controls (42) were injected with 0.02 ml of 0.85% NaCl. Dye-treated embryos examined at three days exhibited a high incidence of hematomas caudal to the leg buds. All embryos examined on or after five days were rumpless. Many embryos examined at four days exhibited an apparently intermediate condition in the development of this defect — a caudal hematoma coupled with beginning degeneration of tail tissues. Histological analysis of these embryos and additional 60 examined and preserved at several intervals (12, 16, 20 and 24 hours) after dye administration suggested the following sequence of events: (1) swelling of the dorsal aortae, (2) bursting of these vessels in the rump, (3) hematoma formation by extravasation from the burst vessels, (4) destruction, by the hematoma, of surrounding rump tissues, (5) resorption of dead or dying tissues, (6) rumplessness. Studies of another series of embryos, each of which was studied in ovo for several days during development, confirmed the destructive effect of a hematoma on morphogenesis of the rump. Dye treated embryos which did not form a caudal hematoma went on to develop a normal rump. Conversely, each embryo which exhibited a caudal hematoma early in development eventually became rumpless.

1. 1. The osmotic pressure and sodium and potassium concentrations were measured in serum samples obtained from 3- to 20-day chick embryos, newly hatched and adult chickens. 2. 2. There are two different levels of serum sodium concentration and osmotic pressure in the life cycle of the chicken. The embryonic levels are 20–30 mequiv./1 lower than that of the adult, and remain relatively constant during the first 2 weeks of development. The transition to adult levels occurs in the first few days after hatching. 3. 3. The serum potassium concentration of the embryo (5·1 mequiv./1) is slightly lower than that of the adult (6·1 mequiv./1) and increases markedly during the perinatal period (8·3 mequiv./1).