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Cortical and hippocampal EEG power spectra in animal models of schizophrenia produced with methamphetamine, cocaine, and phencyclidine.

Cortical and hippocampal EEGs in animal models of schizophrenia were compared to those obtained with psychotomimetics or antipsychotic agents by utilizing power spectral analysis. Models of positive schizophrenic symptoms were created with methamphetamine (MAP) and cocaine, and a model of both negative and positive symptoms was created with PCP. MAP caused a prolonged decrease in the cortical EEG power spectra, cocaine caused a marked decrease for a short time, and PCP produced no significant changes. In the hippocampal spectra, MAP induced a marked increase in the T2(6.0-7.9 Hz)/ T1(4.0-5.9 Hz) ratio, PCP caused a decrease of this ratio after an initial increase, and cocaine produced no significant change. (An increase in the T2/T1 ratio represents a shift of theta waves to higher frequencies.) Since apomorphine (a DA agonist) and MK-801 (an NMDA antagonist) caused the T2/T1 ratio to increase, positive schizophrenic symptoms caused by MAP may be related to the DA and NMDA systems. 3-PPP (a sigma agonist) caused biphasic changes similar to those induced by PCP. Haloperidol and chlorpromazine caused a decrease of the T2/T1 ratio. These results indicate that cortical and hippocampal EEG power spectra (especially the hippocampal T2/T1 ratio) can be used to characterize both qualitatively and quantitatively models of schizophrenia.

Adrenergic Agents↗

Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer's disease.

We investigated the potential mechanisms through which Cerebrolysin, a neuroprotective noothropic agent, might affect Alzheimer's disease pathology. Transgenic (tg) mice expressing mutant human (h) amyloid precursor protein 751 (APP751) cDNA under the Thy-1 promoter (mThy1-hAPP751) were treated for four weeks with this compound and analyzed by confocal microscopy to asses its effects on amyloid plaque formation and neurodegeneration. In this model, amyloid plaques in the brain are found much earlier (beginning at 3 months) than in other tg models. Quantitative computer-aided analysis with anti-amyloid-beta protein (A beta) antibodies, revealed that Cerebrolysin significantly reduced the amyloid burden in the frontal cortex of 5-month-old mice. Furthermore, Cerebrolysin treatment reduced the levels of A beta(1-42). This was accompanied by amelioration of the synaptic alterations in the frontal cortex of mThy1-hAPP751 tg mice. In conclusion, the present study supports the possibility that Cerebrolysin might have neuroprotective effects by decreasing the production of A beta(1-42) and reducing amyloid deposition.

Alzheimer Disease↗

Large-mutation spectra induced at hemizygous loci by low-LET radiation: evidence for intrachromosomal proximity effects.

A mathematical model is used to analyze mutant spectra for large mutations induced by low-LET radiation. The model equations are based mainly on two-break misrejoining that leads to deletions or translocations. It is assumed, as a working hypothesis, that the initial damage induced by low-LET radiation is located randomly in the genome. Specifically, we analyzed data for two hemizygous loci: CD59- mutants, mainly very large-scale deletions (>3 Mbp), in human-hamster hybrid cells, and data from the literature on those HPRT- mutants which involve at least deletion of the whole gene, and often of additional flanking markers (approximately 50-kbp to approximately 4.4-Mbp deletions). For five data sets, we estimated f, the probability that two given breaks on the same chromosome will misrejoin to make a deletion, as a function of the separation between the breaks. We found that f is larger for nearby breaks than for breaks that are more widely separated; i.e., there is a "proximity effect". For acute irradiation, the values of f determined from the data are consistent with the corresponding break misrejoining parameters found previously in quantitative modeling of chromosome aberrations. The value of f was somewhat smaller for protracted irradiation than for acute irradiation at a given total dose; i.e., the mutation data show a decrease that was smaller than expected for dose protraction by fractionation or low dose rate.

Animals↗

In vivo longitudinal assessment of bone resorption in a fibular osteotomy model using micro-computed tomography.

Longitudinal in vivo micro-computerized tomography (CT) imaging was used to monitor bone resorption in a rat fibula osteotomy model. Quantitative image post-processing techniques were developed for spatially aligning the longitudinal data sets. Nominal length and bone volume in the proximal and distal segments of the fibula after the osteotomy were measured, and quantitative comparisons of bone loss over a 13-week period post-surgery were made in five individual rats. A significant decrease in nominal length and bone volume of the distal segment was observed 13 weeks post surgery. A significant decrease in bone volume was also observed in the proximal segment. However, no change in nominal length was observed for the proximal segment of the fibula. This study illustrates the power of this non-invasive technology to measure in vivo small changes in bone length and volume using just a small cohort of animals.

Animals↗

A growth and latency compromised herpes simplex virus type 2 mutant (ICP10DeltaPK) has prophylactic and therapeutic protective activity in guinea pigs.

A growth compromised herpes simplex virus type 2 (HSV-2) mutant which is deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10DeltaPK) protects from fatal HSV-2 challenge in the mouse model (Aurelian L, Kokuba H, Smith CC. Vaccine potential of a Herpes Simplex Virus type 2 mutant deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10). Vaccine 1999;17:1951-1963). Here we report the results of our studies with ICP10DeltaPK in the guinea pig model of recurrent HSV-2 disease. ICP10DeltaPK was also compromised for growth and disease causation in this model. It was not isolated from latently infected ganglia by explant co-cultivation. The proportions of latently infected ganglia were significantly lower for ICP10DeltaPK than HSV-2 [3/25 (12%) and 7/10 (70%), respectively]. Similar results were obtained for the levels of viral DNA (8 x 10(3) and 2 x 10(5) molecules/ganglion for ICP10DeltaPK and HSV-2, respectively]. ICP10DeltaPK immunization caused a significant (P< or = 0.001) decrease in the proportion of animals with primary [1/14 (6%) and 16/16 (100%) for ICP10DeltaPK and PBS, respectively) and recurrent [1/14 (6%) and 11/14 (79%) for ICP10DeltaPK and PBS, respectively) HSV-2 skin lesions. It also protected from genital HSV-2 disease [1/10 and 10/10 for ICP10DeltaPK and PBS, respectively] and decreased the severity of the lesions in both models. Quantitative PCR (Q-PCR) with primers that distinguish between HSV-2 and ICP10DeltaPK indicated that immunization reduced the proportion of ganglia positive for HSV-2 DNA [8/25 (32%) and 7/10 (70%) for ICP10DeltaPK and PBS, respectively) and its levels [3 x 10(3) and 2 x 10(5) molecules/ganglion for ICP10DeltaPK and PBS, respectively]. The proportion of HSV-2 infected animals with recurrent disease was also significantly (P < or = 0.001) decreased by immunization with ICP10DeltaPK [1/15 (7%) and 11/14 (79%) with recurrent disease for ICP10DeltaPK and PBS, respectively], suggesting that ICP10DeltaPK has prophylactic and therapeutic activity in the guinea pig.

Animals↗

Semiautomated resolution of overlapping stutter patterns in genomic microsatellite analysis.

Microsatellites are polymorphic, short nucleotide repeating units scattered more or less randomly throughout the genome. They are readily detectable by polymerase chain reaction (PCR) and often used as genomic markers. One problem in the analysis of microsatellite data is the appearance of secondary bands during PCR that result in extended banding patterns. These "stutter" patterns may overlap in heterozygous alleles and obscure the overall pattern, severely interfering with analysis. This paper develops a model that successfully predicts the general shape of stutter patterns. It then presents techniques for measuring the intensity of the individual contributing alleles. The model is based on the assumption that there is a certain probability of losing or gaining a microsatellite repeat unit during each PCR cycle. The effect is cumulative, with the chance of losing a repeat unit being much greater than that of gaining one, which leads to a gradual reduction in the mean length of the pattern with increased PCR cycles. This can be modeled quantitatively to predict the shape of the stutter pattern, a prediction borne out by experiment. Next, a least-squares technique is presented that is used to analyze the overlapping stutter patterns and determine the relative concentration of each microsatellite in heterozygous alleles. The technique is based on the observation that, at least for microsatellites of approximately the same length, the relative intensity of each band in the stutter pattern is approximately the same for each allele. The stutter shape is most easily determined from homozygous alleles. It can also be approximated from heterozygous samples if the difference between the lengths of the primary microsatellite bands can be determined.

Algorithms↗

Computer simulation of action potentials and afterpotentials in mammalian myelinated axons: the case for a lower resistance myelin sheath.

Depolarizing afterpotentials, recorded in peripheral nerves [Barrett and Barrett (1982) J. Physiol., Lond. 323, 117-144] and spinal axons [Blight and Someya (1985) Neuroscience 15, 1-12], have been interpreted as representing passive discharge of axolemmal capacitance. This interpretation requires a lower resistance pathway through the myelin sheath than previous measurements have suggested. A computer model was used to examine the contribution of the electrical characteristics of nerve fibers to action potential conduction and afterpotential generation. The model consisted of a resistance-capacitance network representing a chain of 20 internodes. The resistances of node, internode and myelin sheath, deduced from observations in the accompanying paper, [Blight and Someya (1985) Neuroscience, 15] were found to produce suitable length and time constants, and prolonged afterpotentials, when inserted into the model. Similar length and time constants were found using a conventional model of the axon, based on measurements from isolated peripheral fibers, but this did not reproduce the afterpotentials. Action-potential conduction velocity is enhanced by reducing the time constant and increasing the length constant. The problem of minimizing the internodal time constant was met in the conventional model through the low parallel resistance of the node, while in the new model it was met by reducing the resistance of the myelin sheath. The latter strategy required the nodal leakage resistance to be higher than values from single fiber measurements (ca 250 M omega rather than ca 50 M omega) in order to maintain the length constant similar to the conventional model. Simulation of the recorded potentials required the resistance of the myelin lamellae to be approx. 100 omega cm2. The model quantitatively reproduced the voltage response of the axon to injected current pulses and to propagated action potentials, using Frankenhaeuser-Huxley kinetics. [Frankenhaeuser and Huxley (1964) J. Physiol., Lond. 171, 302-315; Frankenhaeuser and Moore (1963) J. Physiol., Lond. 169, 431-437]. The short duration components of the afterpotential, observed in mammalian recordings were reproduced by assuming a leakage pathway in the myelin sheath, at the impalement site. The calculated lower resistance of the myelin sheath was such that it minimized the effective internodal time constant for a given nodal resistance. This appears to free the myelinated fiber from the alternative requirement for a high nodal leakage conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Conversion of polarographic electrode measurements--a computer based approach.

The polarographic measurement of tissue oxygenation is one of the most widely used methods in clinical practice for the quantification of tumour hypoxia. However, due to the particular features of the electrode measuring process, the results of the measurements do not accurately reflect the tumour oxygenation. This study aimed to find a correlation between the electrode measurements and the tumour oxygenation in an attempt to improve the accuracy of the predictions regarding the response to treatment based on electrode measurements. A previously developed computer model that allows the simulation of tumour tissue and electrode measurements was used. The oxygenation of a large number of tumours with biologically relevant distributions of blood vessels was theoretically calculated. Simulations of electrode measurements allowed the comparison between the real tissue oxygenation and the results obtained with the electrode. A semi-empirical relationship between the hypoxic fraction measured by the electrode and the real hypoxic fraction in the tissue has been found. The impact of the correction of the electrode measurements in terms of predictions for tumour control probability was estimated for a few clinical examples. The range of possible true values corresponding to one measurement has also proven useful for explaining the apparently unexpected response to the treatment of some patients. The corrected hypoxic fraction which is believed to be closer to the real value of tissue hypoxia predicts much smaller control probabilities than the raw electrode measurements. This could provide an explanation for the apparently unexpected failure to respond to the treatment of some of the patients with apparently favourable tumour oxygenation. This also means that the electrode measurements cannot be used directly for the quantitative modelling of tumour response to the treatment. The conversion method proposed in this paper might however strengthen the statistical power of the correlations between the electrode measurements and the treatment outcome.

Animals↗

Calculations of antibody-antigen interactions: microscopic and semi-microscopic evaluation of the free energies of binding of phosphorylcholine analogs to McPC603.

The study of antibody-antigen interactions should greatly benefit from the development of quantitative models for the evaluation of binding free energies in proteins. The present work addresses this challenge by considering the test case of the binding free energies of phosphorylcholine analogs to the murine myeloma protein McPC603. This includes the evaluation of the differential binding energy as well as the absolute binding energies and their corresponding electrostatic contributions. Four different approaches are examined: the Protein Dipoles Langevin Dipoles (PDLD) method, the semi-microscopic PDLD (PDLD/S) method, a free energy perturbation (FEP) method based on an adiabatic charging procedure and a linear response approximation that accelerates the FEP calculation. The PDLD electrostatic calculations are augmented by estimates of the relevant hydrophobic and steric contributions. The determination of the hydrophobic energy involves an approach which considers the modification of the effective surface area of the solute by local field effects. The steric contributions are analyzed in terms of the corresponding reorganization energies. This treatment, which considers the protein as a harmonic system, views the steric forces as the restoring forces for the electrostatic interactions. The FEP method is found to give unreliable results with regular cut-off radii and starts to give quantitative results only in very expensive treatment with very large cut-off radii. The PDLD and PDLD/S methods are much faster than the FEP approach and give reasonable results for both the relative and absolute binding energies. The speed and simplicity of the PDLD/S method make it an effective strategy for interactive docking studies and indeed such an option is incorporated in the program MOLARIS. A component analysis of the different energy contributions of the FEP treatment and a similar PDLD analysis indicate that electrostatic effects provide the largest contribution to the differential binding energy, while the hydrophobic and steric contributions are much smaller. This finding lends further support to the idea that electrostatic interactions play a major role in determining the antigen specificity of McPC603.

Animals↗

Analogues of virus resistance genes map to QTLs for resistance to sharka disease in Prunus davidiana.

Plum pox virus (PPV), the causative agent of sharka disease in Prunoideae, is one of the most serious problems affecting stone fruit production in Europe and America. Resistance to PPV was previously described in a Prunus davidiana clone, P1908, and introduced into peach (Prunus persica) genotypes. Genetic resistance to PPV displays a complex pattern of quantitative inheritance. An analysis of quantitative trait loci (QTLs) for resistance was performed on an F1 interspecific peach population obtained from a cross between the susceptible nectarine cultivar Summergrand and P. davidiana. The hybrids were graft-inoculated with PPV in duplicate following a classical procedure. The incidence of infection was evaluated four times, over two vegetative cycles, by symptom observation and enzyme-linked immunoadsorbent assays (ELISA). Restriction of systemic downward movement of the PPV virus was also evaluated by testing the susceptible rootstocks. Using both analysis of variance and non-parametric tests, six genomic regions involved in PPV resistance were detected. Depending on the scoring data considered, between 22 and 51% of the phenotypic variance could be explained by the quantitative model. One QTL, located in the distal region of linkage group 1, maps in a genomic region that is syntenic to the location of a resistance gene previously identified in the apricot cv. Goldrich. Some QTLs appeared to be temporally specific, reflecting the environmental dependence of PPV-resistance scoring. Candidate gene fragments were amplified by PCR, isolated and mapped on the peach interspecific linkage map. We report here the co-localization of three analogues of virus resistance genes with two distinct genomic regions linked to PPV resistance in P. davidiana.

Base Sequence↗

Kinetic basis for the voltage-dependent inhibition of N-type calcium current by somatostatin and norepinephrine in chick sympathetic neurons.

Neurotransmitter inhibition of calcium currents (ICa) can be relieved by large depolarizing prepulses. This effect has been postulated to be due either to the voltage-dependent unbinding of an inhibitory molecule from the channel or to a slow voltage-dependent gating step intrinsic to the modulated channel. According to the first hypothesis, the rate of reinhibition (reblock) following a depolarizing prepulse should depend on the concentration of active inhibitory molecules and thus should increase with the extent of inhibition. To distinguish between these models we examined the actions of norepinephrine (NE) and somatostatin (SS) on high-threshold calcium currents in chick sympathetic ganglia, using whole-cell voltage-clamp methods. As previously described in other systems, both NE and SS inhibit omega-conotoxin-sensitive N-type Ca2+ current in a voltage-dependent manner. Pertussis toxin (PTX) pretreatment prevents the inhibition of the current, while replacing GTP in the patch pipette with GTP-gamma-S results in irreversible inhibition, consistent with the involvement of a PTX-sensitive G-protein. The inhibitory responses to NE and SS are not additive, suggesting that they act at a common locus. The inhibitory response to repeated applications of NE or SS desensitizes, with little evidence for cross desensitization. The inhibition of ICa is relieved by a 15 msec prepulse to +100 mV. Following repolarization to -80 mV, ICa slowly reblocks. During prolonged applications of NE or SS the extent of inhibition decreases due to desensitization and reblock kinetics are significantly slowed (time constant increases from 60 msec to > 100 msec for both NE and SS). These results are well fit by a quantitative model in which the kinetics of reblock reflect the binding of an inhibitory molecule to the channel.

4-Aminopyridine↗

Qualitative and quantitative structure-property relationships analysis of multicomponent potential bioglasses.

The results of a qualitative and quantitative structure-property relationships analysis of multicomponent potential bioglasses of composition (2 - y) SiO2 x 1 Na2O x 1.1 CaO x y P2O5 x x ZnO (x = 0, 0.16, 0.35, 0.78 and y = 0.10, 0.20, 0.36) are presented. Quantitative models are obtained by means of structural descriptors derived by molecular dynamics simulations and experimental data measured for density, thermal analysis, 29Si and 31P magic angle spinning NMR, and chemical durability in water. Analysis of the crystal species obtained upon glass crystallization helped in the rationalization of the structural role of the different components. Finally, glass surface characterization with scanning electron microscopy, transmission electron microscopy, and X-ray diffraction after soaking in acellular simulated body fluid demonstrated the in vitro bioactivity of the newly obtained 1.80 SiO2 x 1 Na2O x 1.1 Ca x 0.20 P2O5 x 0.16 ZnO (HP5Z5) glass, corresponding to x = 0.16 and y = 0.20.

Glass↗

A new method for studying the adhesion of Candida albicans to dentin in the presence or absence of smear layer.

OBJECTIVES: The purpose of this study was to develop a reproducible, quantitative model of Candida albicans adhesion to human dentin through the use of a colorimetric method and to evaluate the effect of smear layer on candidal adhesion. STUDY DESIGN: Dentin disks with or without smear layer were incubated with C albicans (10(8) cells/mL) for 4 hours. After incubation, the disks were exposed to an (2,3)-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium hydroxide-coenzyme Q solution for 2 hours. The color of (2,3)-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium hydroxide formazan in the supernatant was determined spectrophotometrically at 492 nm. To relate formazan formation to cell numbers, standard curves were generated with known numbers of yeast cells without dentin. The number of adherent cells per square millimeter was then calculated. RESULTS: The number of attached C albicans cells was 2.4 x 10(4) per square millimeter in dentin with smear layer and 1.5 x 10(4) in dentin without smear layer (P <.05). CONCLUSION: (2,3)-Bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium hydroxide assay is a potential microbiologic tool for the quantitative determination of Candida adhesion to human dentin.

Candida albicans↗

Thallium-201 scintigraphic quantitation of regional flow disparity and subsequent redistribution in dogs.

Although quantitative analysis of postexercise thallium-201 (201Tl) scintigrams has been employed clinically for the diagnosis of coronary disease, the precise relationship of the quantitated defects to microsphere determined blood flow has not been determined. Accordingly, 201Tl was injected during exercise in 12 control dogs and seven with left circumflex (LCf) artery stenosis. Gamma camera scanning was started 10 min after 201Tl injection and continued for 3 hr. In the control animals, scintigraphic 201Tl activities in left anterior descending (LAD) and LCf perfusion territories were equal 10 min after 201Tl injection and the loss of 201Tl activity over 3 hr was 54.3 +/- 3.4% and 57.0 +/- 3.6% (mean +/- s.e.e.) of initial LAD and LCf activity, respectively (p = N.S.). In the experimental group, LCf activity 10-14 min after 201Tl injection averaged 67.4 +/- 5.9% of LAD activity in the same heart (p less than 0.001). Furthermore, LCf activity in the experimental animals was significantly lower than LCf activity in the control dogs (p less than 0.005), while LAD activities were not different in the two groups. The ratio of LCf/LAD scintigraphic 201Tl activity immediately after exercise was linearly related to, but higher than, the ratio of regional blood flows at peak exercise (r = 0.88, p less than 0.001) as determined by microsphere injection. Scintigraphic redistribution was also correlated with directly measured redistribution determined by well counter analysis (r = 0.83, p less than 0.025). Thus, in this exercise model, quantitative 201Tl scintigraphy accurately assessed the initial postexercise flow disparity and subsequent redistribution.

Animals↗

Effects of mesh style and grid convergence on particle deposition in bifurcating airway models with comparisons to experimental data.

A number of research studies have employed a wide variety of mesh styles and levels of grid convergence to assess velocity fields and particle deposition patterns in models of branching biological systems. Generating structured meshes based on hexahedral elements requires significant time and effort; however, these meshes are often associated with high quality solutions. Unstructured meshes that employ tetrahedral elements can be constructed much faster but may increase levels of numerical diffusion, especially in tubular flow systems with a primary flow direction. The objective of this study is to better establish the effects of mesh generation techniques and grid convergence on velocity fields and particle deposition patterns in bifurcating respiratory models. In order to achieve this objective, four widely used mesh styles including structured hexahedral, unstructured tetrahedral, flow adaptive tetrahedral, and hybrid grids have been considered for two respiratory airway configurations. Initial particle conditions tested are based on the inlet velocity profile or the local inlet mass flow rate. Accuracy of the simulations has been assessed by comparisons to experimental in vitro data available in the literature for the steady-state velocity field in a single bifurcation model as well as the local particle deposition fraction in a double bifurcation model. Quantitative grid convergence was assessed based on a grid convergence index (GCI), which accounts for the degree of grid refinement. The hexahedral mesh was observed to have GCI values that were an order of magnitude below the unstructured tetrahedral mesh values for all resolutions considered. Moreover, the hexahedral mesh style provided GCI values of approximately 1% and reduced run times by a factor of 3. Based on comparisons to empirical data, it was shown that inlet particle seedings should be consistent with the local inlet mass flow rate. Furthermore, the mesh style was found to have an observable effect on cumulative particle depositions with the hexahedral solution most closely matching empirical results. Future studies are needed to assess other mesh generation options including various forms of the hybrid configuration and unstructured hexahedral meshes.

Computer Simulation↗

Microbiology in nuclear waste disposal: interfaces and reaction fronts.

It is now generally acknowledged that microbial populations will be present within nuclear waste repositories and that the consequences of such activity on repository performance must be assessed. Various modelling approaches--based either on mass balance/thermodynamics or on kinetics--have been developed to provide scoping estimates of the possible development of these populations. Past work has focused on particular areas of the repository which can be considered relatively homogeneous and hence can be represented by some kind of 'box' or 'mixing tank'. In reality, however, waste repositories include a range of engineering materials (steel, concrete, etc.) which are emplaced at depth in a rock formation. Strong chemical gradients--of the type which may be exploited by lithoautotrophic microbial populations--are likely to be found at the contacts between different materials and at the interface between the engineered structures and the host rock. Over the long timescales considered, solute transport processes will cause the locations of strong chemical gradients to move, forming reaction fronts. The high-pH plume resulting from the leaching of cement/concrete in some repository types is a particularly important example of such a reaction front. Redox fronts, which may occur in different areas of all kinds of repositories, also play an important role and would be locations where microbial activity is likely to be significant. In this paper, the key microbial processes expected at (or around) interfaces and fronts will be discussed, with particular emphasis on the development of quantitative models. The applicability of the models used wil be tested by considering similar fronts which can be found in natural systems.

Biodegradation, Environmental↗

Analysis of epidemiological peculiarities of rubella based on a mathematical model (according to observations over 10 years in Moscow).

The main epidemiological values characterizing rubella in Moscow were calculated on the basis of a new mathematical model. Quantitative estimates of the intensity of infection in different age groups of the population were obtained. It has been established that the risk of infection in children is especially high in comparison with adult population. That is why 98% of the population aged 15 are immune. The probability of falling ill with rubella was determined for persons with different antibody levels. The cases of congenital rubella in Moscow are rare due to the low risk of infection in adults and to their immunity acquired in childhood. Consequently, there is no necessity for vaccination against rubella in Moscow at the present time, but it should be recommended to organize constant epidemiological surveillance of congenital rubella.

Adolescent↗

Immunocontraception for population control: will resistance evolve?

The prospect for successful biocontrol using immunocontraception is threatened if there is adaptation to the vaccine through natural selection of individuals that are genetically resistant to the contraceptive agent. To assess this possibility we examined the literature and found that little relevant data are available for any species on the appropriate trait, fertility variation among immunized individuals, or about appropriate population and genetic parameters influencing the likelihood of a selection response. Some data are available on variation in antibody response to immunocontraceptives, but the relationship between antibody response and fertility levels is poorly documented. The antibody response data indicate low heritability for this trait suggesting that fertility levels of contraceptive-resistant individuals will also have a low heritability. Slow evolution of contraception resistance might therefore be anticipated. The absence of information about relevant parameters makes the construction of quantitative models premature. We discuss factors in particular need of investigation if predictions about resistance evolution are to be made. These include: 1. the genetic basis of fertility retention, 2. the proportion of the population resistant to the contraceptive agent and how this is affected by gene flow from refuge populations, 3. the genetically-based fitness tradeoffs of resistant individuals that often accompany selection, 4. cross-generation effects that can thwart the effects of selection, and 5. the efficiency of delivery of the contraceptive agent. An understanding of the above for particular species, and the development of appropriate divergently acting multiple vaccines that can be used in temporal rotation or in mixtures, should facilitate the development of management options to minimize resistance evolution.

Animals↗