Autoprobiotics in the Treatment of Patients with Colorectal Cancer in the Early Postoperative Period.

Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics, remains relevant. The aim of this study is to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae as a personalized functional food product (PFFP) in the complex therapy of colorectal cancer (CRC) in the early postoperative period. A total of 36 patients diagnosed with CRC were enrolled in the study. Study group A comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group C included 12 CRC patients without autoprobiotic therapy. Prior to surgery and between days 14 and 16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complaints analysis, examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), and analysis of interleukins in the serum. Results: The use of autoprobiotics led to a decrease in dyspeptic complaints after surgery. It was also associated with the absence of postoperative complications, did not cause any side effects, and led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra and Fusobacterium nucleatum, and a decrease in the quantitative content of Clostridium perfringens and Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The introduction of autoprobiotics in the postoperative period is a highly effective and safe approach in the complex treatment of CRC. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine, and neural systems.

Association of Increased Homocysteine Levels with Impaired Folate Metabolism and Vitamin B Deficiency in Early-Onset Multiple Sclerosis.

The contents of homocysteine (HCy), cyanocobalamin (vitamin B12), folic acid (vitamin B9), and pyridoxine (vitamin B6) were analyzed and the genotypes of the main gene polymorphisms associated with folate metabolism (C677T and A1298C of the MTHFR gene, A2756G of the MTR gene and A66G of the MTRR gene) were determined in children at the onset of multiple sclerosis (MS) (with disease duration of no more than six months), healthy children under 18 years (control group), healthy adults without neurological pathology, adult patients with MS at the onset of disease, and adult patients with long-term MS. A significant increase in the HCy levels was found in children at the MS onset compared to healthy children of the corresponding age. It was established that the content of HCy in children has a high predictive value. At the same time, an increase in the HCy levels was not accompanied by the deficiency of vitamins B6, B9, and B12 in the blood. The lack of correlation between the laboratory signs of vitamin deficiency and HCy levels may be due to the polymorphic variants of folate cycle genes. An increased HCy level should be considered as a marker of functional disorders of folate metabolism accompanying the development of pathological process in pediatric MS. Our finding can be used to develop new approaches to the prevention of demyelination in children and treatment of pediatric MS.

Diabetes-Induced Changes of the Rat ERG in Relation to Hyperglycemia and Acidosis.

PURPOSE: To understand the mechanism of changes in the c-wave of the electroretinogram (ERG) in diabetic rats, and to explore how glucose manipulations affect the c-wave. METHODS: Vitreal ERGs were recorded in control and diabetic Long-Evans rats, 3-60 weeks after IP vehicle or streptozotocin. A few experiments were performed on Brown Norway rats. Voltage responses to current pulses were used to measure the transepithelial resistance of the retinal pigment epithelium (RPE). RESULTS: During development of diabetes the b-wave amplitude progressively decreased to about half of the initial amplitude after a year. In contrast, the c-wave was strongly affected from the very beginning (3 weeks) of diabetes. In control rats, the c-wave was cornea-positive at lower illuminations but was cornea-negative at higher (photopic) illumination. In diabetics, the whole amplitude-intensity curve was shifted toward negativity. The magnitude of this shift was markedly affected by acute glucose manipulations in diabetics but not in controls. Increased blood glucose made the c-wave more negative, and decreased blood glucose with insulin had the opposite effect. Experimentally induced acidification of the retina had a small effect that was different from diabetes, shifting the c-wave toward positivity, slightly in controls and more noticeably in diabetics. One reason for the significant negativity of the diabetic ERG was a decrease of the cornea-positive response of the RPE due to a decrease of the transepithelial resistance. CONCLUSIONS: The ERG c-wave is more negative in diabetics than in control animals, and is far more sensitive to changes in blood glucose. The increased negativity is largely if not entirely due to changes in the transepithelial resistance of the RPE, an electrical analog of the breakdown of the blood-retinal barrier observed in other studies. The sensitivity of the c-wave to glucose in diabetics may also be due to changes in transepithelial resistance.

MetaTox 2.0: Estimating the Biological Activity Spectra of Drug-like Compounds Taking into Account Probable Biotransformations.

After the biotransformation of xenobiotics in the human body, the biological activity of the metabolites may differ from the activity of parent compounds. Therefore, to assess the overall biological activity of a drug-like compound, it is important to take into account its metabolites and their biological activity. We developed MetaTox 2.0-an updated version of the MetaTox web application that was able to predict the metabolites of xenobiotics. Innovations include estimating the biological activity profile of a compound and taking into account its metabolites. The estimation is based on the PASS (prediction of activity spectra for substances) algorithm and on the latest version of the training set covering over 1900 biological activities predicted with an average accuracy exceeding 0.97. Also, MetaTox 2.0 allows the search for similar substances among more than 2000 drugs with known metabolic networks, which were extracted from the ChEMBL, MetXBIODB, and DrugBank databases. MetaTox 2.0 is freely available on the web at https://www.way2drug.com/metatox.

Open and Percutaneous Trigeminal Nucleotractotomy: A Case Series and Literature Review.

INTRODUCTION: Nucleotractotomy is an efficient surgical technique that provides a high pain relief rate for specific clinical indications. There are two main approaches for performing this operation: an open and percutaneous technique. METHODS: In the Federal Center of Neurosurgery (Novosibirsk, Russia) from 2016 to 2022, 13 trigeminal nucleotractotomies (7 open and 6 percutaneous) were performed in 12 patients (5 women and 7 men). The indications for surgery were deafferentation pain and chronic drug-resistant pain syndrome caused by malignancy in the facial region. A neurological examination was done on each patient 1 day before the surgery, right after the surgery, and at the follow-up (examinations were done after 1, 6, and 12 months, or when the patient independently applied to our hospital). In the early postoperative period, patients underwent brain MRI. RESULTS: The average pain intensity score before nucleotractotomy on the 11-point (0-10) visual analog scale (VAS) was 9.3. The effectiveness of open interventions was somewhat higher; the average VAS score in the early postoperative period for the open technique was 1.57, in the group of patients who underwent percutaneous nucleotractotomy were 2.66. Complete regression of the pain syndrome was achieved in 6 patients; in 5 patients, the pain in the face decreased by more than 50%. One case had an unsatisfactory outcome. In the open-surgery group in the early postoperative period, according to MRI, the average length of the visualized area of signal change was longer (21.5 mm, the average diameter was 3.75 mm) than in a percutaneous nucleotractotomy group (16 mm, the average diameter was 3.75 mm). During the postoperative period (average follow-up 40 months), the pain recurred in 3 patients (30%): 2 patients after percutaneous nucleotractotomy (3 and 18 months after surgery) and in 1 patient 4 months after the open surgery. The mean VAS score at the last follow-up was 2.6. CONCLUSION: Trigeminal nucleotractotomy is an effective approach to the treatment of intractable facial pain. Our experience suggests this technique is highly effective in patients with drug-resistant pain caused by craniofacial tumors and deafferentation conditions after treating trigeminal neuralgia.

Signal Mediators in the Implementation of Jasmonic Acid's Protective Effect on Plants under Abiotic Stresses.

Plant cells respond to stress by activating signaling and regulatory networks that include plant hormones and numerous mediators of non-hormonal nature. These include the universal intracellular messenger calcium, reactive oxygen species (ROS), gasotransmitters, small gaseous molecules synthesized by living organisms, and signal functions such as nitrogen monoxide (NO), hydrogen sulfide (H2S), carbon monoxide (CO), and others. This review focuses on the role of functional linkages of jasmonic acid and jasmonate signaling components with gasotransmitters and other signaling mediators, as well as some stress metabolites, in the regulation of plant adaptive responses to abiotic stressors. Data on the involvement of NO, H2S, and CO in the regulation of jasmonic acid formation in plant cells and its signal transduction were analyzed. The possible involvement of the protein components of jasmonate signaling in stress-protective gasotransmitter effects is discussed. Emphasis is placed on the significance of the functional interaction between jasmonic acid and signaling mediators in the regulation of the antioxidant system, stomatal apparatus, and other processes important for plant adaptation to abiotic stresses.

Oxygen profiles and oxygen consumption in the isolated mouse retina.

The retina has a large demand for oxygen, but there is only limited information on differences between oxygen utilization (QO2) in the inner and outer retina, and limited data on mouse, which has become a prevalent animal model. This study utilized the isolated mouse retina, which allowed more detailed spatial analysis of QO2 than other methods. Oxygen sensitive microelectrodes were used to obtain profiles of oxygen tension across the isolated mouse retina, and mathematical models of retinal oxygen diffusion with four and five layers were fitted to the data to obtain values for QO2 of the outer retina (QOR) and inner retina (QIR). The boundaries between layers were free parameters in these models. The five-layer model resulted in lower error between the model and data, and agreed better with known anatomy. The three layers for the outer retina occupied half of the retina, as in prior work on rat, cat, and monkey, and the inner half of the retina could be divided into two layers, in which the one closer to the vitreous (layer 5) had much lower QO2 than the more distal inner retina (layer 4). QIR in darkness was 3.9 ml O2-100 g-1-min-1, similar to the value for intact cat retina, and did not change during light. QOR in darkness was 2.4 ml O2-100 g-1-min-1, lower than previous values in cat and rat, possibly because of damage to photoreceptors during isolation. There was a tendency for QOR to be lower in light, but it was not significant in this preparation.

Prediction of Adverse Effects of Drug-Drug Interactions on Cardiovascular System Based on the Analysis of Structure-Activity Relationships.

Co-administration of drugs often leads to drug-drug interactions, which could be accompanied by various adverse drug reactions that pose a threat to life and health of the patient. The effect caused by adverse drug reactions on cardiovascular system is one of the most significant manifestations of drug-drug interaction. Clinical assessment of adverse drug reactions resulting from drug-drug interaction between all drug pairs used in therapeutic practice is not possible. The purpose of this work was to build models using structure-activity analysis to predict adverse effects of drugs on cardiovascular system, mediated by pairwise interactions between the drug pairs when they are taken together. Data on the adverse effects resulting from drug-drug interaction were obtained from the DrugBank database. The data on drug pairs that do not cause such effects, which are necessary for building accurate structure-activity models, were obtained from the TwoSides database, which contains the results of analysis of the spontaneous reports. Two types of descriptors were used to describe a pair of drug structures: PoSMNA descriptors and probabilistic estimates of the prediction of biological activities obtained using the PASS program. Structure-activity relationships were established using the Random Forest method. Prediction accuracy was calculated by means of five-fold cross-validation. The highest accuracy values were obtained using PASS probabilistic estimates as descriptors. The area under the ROC curve was 0.94 for bradycardia, 0.96 for tachycardia, 0.90 for arrhythmia, 0.90 for ECG QT prolongation, 0.91 for hypertension, 0.89 for hypotension.

A Genome of Temperate Enterococcus Bacteriophage Placed in a Space of Pooled Viral Dark Matter Sequences.

In the human gut, temperate bacteriophages interact with bacteria through predation and horizontal gene transfer. Relying on taxonomic data, metagenomic studies have associated shifts in phage abundance with a number of human diseases. The temperate bacteriophage VEsP-1 with siphovirus morphology was isolated from a sample of river water using Enterococcus faecalis as a host. Starting from the whole genome sequence of VEsP-1, we retrieved related phage genomes in blastp searches of the tail protein and large terminase sequences, and blastn searches of the whole genome sequences, with matches compiled from several different databases, and visualized a part of viral dark matter sequence space. The genome network and phylogenomic analyses resulted in the proposal of a novel genus "Vespunovirus", consisting of temperate, mainly metagenomic phages infecting Enterococcus spp.

CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds.

In vitro cell-line cytotoxicity is widely used in the experimental studies of potential antineoplastic agents and evaluation of safety in drug discovery. In silico estimation of cytotoxicity against hundreds of tumor cell lines and dozens of normal cell lines considerably reduces the time and costs of drug development and the assessment of new pharmaceutical agent perspectives. In 2018, we developed the first freely available web application (CLC-Pred) for the qualitative prediction of cytotoxicity against 278 tumor and 27 normal cell lines based on structural formulas of 59,882 compounds. Here, we present a new version of this web application: CLC-Pred 2.0. It also employs the PASS (Prediction of Activity Spectra for Substance) approach based on substructural atom centric MNA descriptors and a Bayesian algorithm. CLC-Pred 2.0 provides three types of qualitative prediction: (1) cytotoxicity against 391 tumor and 47 normal human cell lines based on ChEMBL and PubChem data (128,545 structures) with a mean accuracy of prediction (AUC), calculated by the leave-one-out (LOO CV) and the 20-fold cross-validation (20F CV) procedures, of 0.925 and 0.923, respectively; (2) cytotoxicity against an NCI60 tumor cell-line panel based on the Developmental Therapeutics Program's NCI60 data (22,726 structures) with different thresholds of IG50 data (100, 10 and 1 nM) and a mean accuracy of prediction from 0.870 to 0.945 (LOO CV) and from 0.869 to 0.942 (20F CV), respectively; (3) 2170 molecular mechanisms of actions based on ChEMBL and PubChem data (656,011 structures) with a mean accuracy of prediction 0.979 (LOO CV) and 0.978 (20F CV). Therefore, CLC-Pred 2.0 is a significant extension of the capabilities of the initial web application.

Combined Use of Antimicrobial Peptides with Antiseptics against Multidrug-Resistant Bacteria: Pros and Cons.

Antimicrobial peptides (AMPs) are acknowledged as a promising template for designing new antimicrobials. At the same time, existing toxicity issues and limitations in their pharmacokinetics make topical application one of the less complicated routes to put AMPs-based therapeutics into actual medical practice. Antiseptics are one of the common components for topical treatment potent against antibiotic-resistant pathogens but often with toxicity limitations of their own. Thus, the interaction of AMPs and antiseptics is an interesting topic that is also less explored than combined action of AMPs and antibiotics. Herein, we analyzed antibacterial, antibiofilm, and cytotoxic activity of combinations of both membranolytic and non-membranolytic AMPs with a number of antiseptic agents. Fractional concentration indices were used as a measure of possible effective concentration reduction achievable due to combined application. Cases of both synergistic and antagonistic interaction with certain antiseptics and surfactants were identified, and trends in the occurrence of these types of interaction were discussed. The data may be of use for AMP-based drug development and suggest that the topic requires further attention for successfully integrating AMPs-based products in the context of complex treatment. AMP/antiseptic combinations show promise for creating topical formulations with improved activity, lowered toxicity, and, presumably, decreased chances of inducing bacterial resistance. However, careful assessment is required to avoid AMP neutralization by certain antiseptic classes in either complex drug design or AMP application alongside other therapeutics/care products.

Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450.

Human cytochrome P450 enzymes (CYPs) are heme-containing monooxygenases. This superfamily of drug-metabolizing enzymes is responsible for the metabolism of most drugs and other xenobiotics. The inhibition of CYPs may lead to drug-drug interactions and impair the biotransformation of drugs. CYP inducers may decrease the bioavailability and increase the clearance of drugs. Based on the freely available databases ChEMBL and PubChem, we have collected over 70,000 records containing the structures of inhibitors and inducers together with the IC50 values for the inhibitors of the five major human CYPs: 1A2, 3A4, 2D6, 2C9, and 2C19. Based on the collected data, we developed (Q)SAR models for predicting inhibitors and inducers of these CYPs using GUSAR and PASS software. The developed (Q)SAR models could be applied for assessment of the interaction of novel drug-like substances with the major human CYPs. The created (Q)SAR models demonstrated reasonable accuracy of prediction. They have been implemented in the web application P450-Analyzer that is freely available via the Internet.

Consortium of Indigenous Fecal Bacteria in the Treatment of Metabolic Syndrome.

The features of gut microbiota in metabolic syndrome (MS) and ways to correct it using autoprobiotics, based on indigenous bacteria obtained from fecal samples of the host, remain unexplored. The aim of the study was to investigate the effectiveness of an indigenous consortium (IC) of fecal bacteria in treatment of patients with MS. The study was carried out on 36 patients with MS, manifested with abdominal obesity, eating disorders, dyslipidemia, and hypertension. The control group was formed by 20 healthy volunteers. Samples of IC and gut microbiota content were examined by qPCR and metagenome (16S rRNA) analysis before and after therapy. The decrease in anthropometric parameters of obesity, liver enzyme level correction, reduction in C reactive protein and triglyceride concentrations were revealed after IC usage. The decrease in genera Bifidobacterium, Enterobacter, Paraprevotella, and Prevotella, as well as an increase in Bacteroides fragilis and Oscillospira spp. populations were shown after consumption of IC. A negative correlation between the quantity of B. fragilis and the anthropometric parameters of obesity (r = -0.48) and C reactive protein level (r = -0.36) in serum was established. Thus, IC can be considered as a potential functional personified product for the therapy of MS.

Metformin Influence on the Intestinal Microbiota and Organism of Rats with Metabolic Syndrome.

Metformin is a first-line drug for DM2 treatment and prevention, but its complex effect on impaired glucose tolerance (IGT), including its influence on myocardial resistance to ischemia-reperfusion injury, is not completely studied. We aimed to evaluate the influence of metformin on the intestinal microbiota (IM), metabolism, and functional and morphological characteristics of myocardium in rats with IGT. IGT was modelled in SPF Wistar rats with a high-fat diet and streptozotocin and nicotinamide injection. Rats were divided into three groups: IGT (without treatment), IGT MET (metformin therapy), and CRL (without IGT induction and treatment). IGT group was characterized by: higher body weight, increased serum glucose and total cholesterol levels, atherogenic coefficient, impairment in the functional parameters of the isolated heart during perfusion, and larger myocardium infarction (MI) size in comparison with the CRL group. IM of IGT rats differed from that of CRL: an increase of Bacteroides, Acinetobacter, Akkermansia, Roseburia, and a decrease of Lactobacillus genera representation. Metformin therapy led to the diminishing of metabolic syndrome (MS) symptoms, which correlated with IM restoration, especially with the growth of Akkermansia spp. and decline of Roseburia populations and their influence on other members of IM. The obtained results allow us to consider from a new point of view the expediency of probiotic A. muciniphila use for MS treatment.

Extracellular K+ reflects light-evoked changes in retinal energy metabolism.

Retinal neurons spend most of their energy to support the transmembrane movement of ions. Light-induced electrical activity is associated with a redistribution of ions, which affects the energy demand and results in a change in metabolism. Light-induced metabolic changes are expected to be different in distal and proximal retina due to differences in the light responses of different retinal cells. Extracellular K+ concentration ([K+]o) is a reliable indicator of local electrophysiological activity, and the purpose of this work was to compare [K+]o changes evoked by steady and flickering light in distal and proximal retina. Data were obtained from isolated mouse (C57Bl/6J) retinae. Double-barreled K+-selective microelectrodes were used to simultaneously record [K+]o and local ERGs. In the distal retina, photoreceptor hyperpolarization led to suppression of ion transfer, a decrease in [K+]o by 0.3-0.5 mM, reduced energy demand, and, as previously shown in vivo, decreased metabolism. Flickering light had the same effect on [K+]o in the distal retina as steady light of equivalent illumination. The conductance and voltage changes in postreceptor neurons are cell-specific, but the overall effect of steady light in the proximal retina is excitation, which is reflected in a [K+]o increase there (by a maximum of 0.2 mM). In steady light the [K+]o increase lasts only 1-2 s, but a sustained [K+]o increase is evoked by flickering light. A squarewave low frequency (1 Hz) flicker of photopic intensity produced the largest increases in [K+]o. Judging by measurements of [K+]o, steady illumination decreases energy metabolism in the distal retina, but not in the proximal retina (except for the first few seconds). Flickering light evokes the same decrease in the distal retina, but also evokes a sustained [K+]o increase in the proximal retina, suggesting an increase of metabolic demand there, especially at 1 Hz, when neurons of both on- and off-pathways appear to contribute maximally. This proximal retinal metabolic response to flicker correlates to the increase in blood flow during flicker that constitutes neurovascular coupling.

Two Novel Lytic Bacteriophages Infecting Enterococcus spp. Are Promising Candidates for Targeted Antibacterial Therapy.

The rapid emergence of antibiotic resistance is of major concern globally. Among the most worrying pathogenic bacteria are vancomycin-resistant enterococci. Phage therapy is a highly promising method for controlling enterococcal infections. In this study, we described two virulent tailed bacteriophages possessing lytic activity against Enterococcus faecalis and E. faecium isolates. The SSsP-1 bacteriophage belonged to the Saphexavirus genus of the Siphoviridae family, and the GVEsP-1 bacteriophage belonged to the Schiekvirus genus of Herelleviridae. The genomes of both viruses carried putative components of anti-CRISPR systems and did not contain known genes coding for antibiotic-resistance determinants and virulence factors. The conservative arrangement of protein-coding sequences in Saphexavirus and Schiekvirus genomes taken together with positive results of treating enterococcal peritonitis in an animal infection model imply the potential suitability of GVEsP-1 and SSsP-1 bacteriophages for clinical applications.

Formation of color solitons and domains in fiber lasers.

Using numerical simulation, we have investigated the generation of color solitons consisting of two radiation fragments with different carrier frequencies in a dual-wavelength laser. The proposed mechanism for the formation of such solitons involves nonlinear losses that increase with increasing intensity, the dispersion of the refractive index, spectral gain inhomogeneity, and the generation of a doublet radiation spectrum, owing to the corresponding spectral-dependent losses in the laser. The proposed theory explains the main features of the experimentally observed formation of color domains in fiber lasers and has the potential for further development of methods for controlling the nonlinear dynamics of laser radiation.

Label-Free Physical Techniques and Methodologies for Proteins Detection in Microfluidic Biosensor Structures.

Proteins in biological fluids (blood, urine, cerebrospinal fluid) are important biomarkers of various pathological conditions. Protein biomarkers detection and quantification have been proven to be an indispensable diagnostic tool in clinical practice. There is a growing tendency towards using portable diagnostic biosensor devices for point-of-care (POC) analysis based on microfluidic technology as an alternative to conventional laboratory protein assays. In contrast to universally accepted analytical methods involving protein labeling, label-free approaches often allow the development of biosensors with minimal requirements for sample preparation by omitting expensive labelling reagents. The aim of the present work is to review the variety of physical label-free techniques of protein detection and characterization which are suitable for application in micro-fluidic structures and analyze the technological and material aspects of label-free biosensors that implement these methods. The most widely used optical and impedance spectroscopy techniques: absorption, fluorescence, surface plasmon resonance, Raman scattering, and interferometry, as well as new trends in photonics are reviewed. The challenges of materials selection, surfaces tailoring in microfluidic structures, and enhancement of the sensitivity and miniaturization of biosensor systems are discussed. The review provides an overview for current advances and future trends in microfluidics integrated technologies for label-free protein biomarkers detection and discusses existing challenges and a way towards novel solutions.

K+-dependent Müller cell-generated components of the electroretinogram.

The electroretinogram (ERG) has been employed for years to collect information about retinal function and pathology. The usefulness of this noninvasive test depends on our understanding of the cell sources that generate the ERG. Important contributors to the ERG are glial Müller cells (MCs), which are capable of generating substantial transretinal potentials in response to light-induced changes in extracellular K+ concentration ([K+]o). For instance, the MCs generate the slow PIII (sPIII) component of the ERG as a reaction to a photoreceptor-induced [K+]o decrease in the subretinal space. Similarly, an increase of [K+]o related to activity of postreceptor retinal neurons also produces transretinal glial currents, which can potentially influence the amplitude and shape of the b-wave, one of the most frequently analyzed ERG components. Although it is well documented that the majority of the b-wave originates from On-bipolar cells, some contribution from MCs was suggested many years ago and has never been experimentally rejected. In this work, detailed information about light-evoked [K+]o changes in the isolated mouse retina was collected and then analyzed with a relatively simple linear electrical model of MCs. The results demonstrate that the cornea-positive potential generated by MCs is too small to contribute noticeably to the b-wave. The analysis also explains why MCs produce the large cornea-negative sPIII subcomponent of the ERG, but no substantial cornea-positive potential.