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The background of this study is to evaluate the impact of the assistant surgeon's in robotic-assisted proctectomy (RAP) on perioperative outcomes. A retrospective analysis of all patients who underwent RAP for rectal adenocarcinoma between 2011 and 2020 was conducted. Patient cohort was divided into three groups based on the assistant surgeon's training level: post-graduate years (PGY) 1-3 surgical residents (Group 1), PGY 4-5 surgical residents (Group 2), and board-certified general surgeons (Group 3). Overall, 175 patients were included in the study: 29 patients (17%) in Group 1, 84 (48%) in Group 2, and 62 (35%) in Group 3. The median tumor distance from the anal verge was 8 cm in all groups (p = 0.73). The median operative time was similar across all groups: 290, 291, and 281 min in Groups 1, 2, and 3, respectively (p = 0.69). In a multivariable analysis, the lack of association between assistant training level and procedure time maintained when adjusting for the year of operation (p = 0.84). Patients operated with junior residents as assistant surgeons (Group 1) had a more postoperative complications (p = 0.01) and a slightly longer hospital length of stay [7 days, interquartile range (IQR) 3], compared to those operated by assistant surgeons that were senior residents or attendings (6 IQR 2.5, and 6 IQR 2 in Groups 2 and 3, respectively; p = 0.02). Conversion rates (p = 0.12), intraoperative complications (p = 0.39), major postoperative complications (Clavien-Dindo ≥ 3; p = 0.32), 30-day readmission (p = 0.45), and mortality (p = 0.99) were similar between the groups. Robotic-assisted proctectomy performed with the assistance of a junior resident was found to be correlated with worse postoperative outcomes compared to more experienced assistants. No difference was seen in intraoperative outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Visceral peritoneal colorectal metastases (VPCMs) may further metastasize to lymph nodes that drain those organs. The rate of lymph node metastases (LNMs) from VPCMs and their clinical and prognostic significance are unknown., Methods: This study retrospectively analyzed the authors' institutional databases of 160 patients with peritoneal colorectal metastases who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Patients with LNM-VPCM (n = 12) were identified by pathologic reports, and both their short- and long-term outcomes were compared with those of patients without LNM-VPCM., Results: The clinical presentation and primary tumor pathologic characteristics did not differ between the two groups. The patients with LNM-VPCM had a higher tumor burden (measured by the peritoneal carcinomatosis index [PCI]) and visible remnant disease compared with those who had no LNM-VPI (10 vs 5.5 [p = 0.03] vs 33.3% vs 6.8% [p = 0.007], respectively). The postoperative outcomes also were comparable. The patients with LNM-VPCM had a shorter overall survival (OS) than those without LNM-VPCM (median OS, 22.5 months; 95% confidence interval [CI], 15.1-29.9 months vs 40.1 months; 95% CI, 38.1-42 months; p = 0.02). However, only tumor grade and PCI were predictors of OS in the multivariate analysis (hazard ratio [HR], 2.33 [p = 0.001]; 1.77 [p = 0.03], respectively). The study showed that LNM-VPCM was associated with systemic but not peritoneal recurrence compared with non-LNM-VPCM (81.8% vs 51.6% for systemic recurrence, respectively; p = 0.05)., Conclusion: The small distinct group of patients defined by LNM-VPCM were prone to systemic recurrence. Given its correlation with systemic recurrence, LNM-VPCM may indicate the need for adjuvant treatment., (© 2021. Society of Surgical Oncology.)

Background: In the past decade, deep learning has revolutionized medical image processing. This technique may advance laparoscopic surgery. Study objective was to evaluate whether deep learning networks accurately analyze videos of laparoscopic procedures., Methods: Medline, Embase, IEEE Xplore, and the Web of science databases were searched from January 2012 to May 5, 2020. Selected studies tested a deep learning model, specifically convolutional neural networks, for video analysis of laparoscopic surgery. Study characteristics including the dataset source, type of operation, number of videos, and prediction application were compared. A random effects model was used for estimating pooled sensitivity and specificity of the computer algorithms. Summary receiver operating characteristic curves were calculated by the bivariate model of Reitsma., Results: Thirty-two out of 508 studies identified met inclusion criteria. Applications included instrument recognition and detection (45%), phase recognition (20%), anatomy recognition and detection (15%), action recognition (13%), surgery time prediction (5%), and gauze recognition (3%). The most common tested procedures were cholecystectomy (51%) and gynecological-mainly hysterectomy and myomectomy (26%). A total of 3004 videos were analyzed. Publications in clinical journals increased in 2020 compared to bio-computational ones. Four studies provided enough data to construct 8 contingency tables, enabling calculation of test accuracy with a pooled sensitivity of 0.93 (95% CI 0.85-0.97) and specificity of 0.96 (95% CI 0.84-0.99). Yet, the majority of papers had a high risk of bias., Conclusions: Deep learning research holds potential in laparoscopic surgery, but is limited in methodologies. Clinicians may advance AI in surgery, specifically by offering standardized visual databases and reporting.

Background: This study aimed to examine the correlation between intraoperative and pathological findings for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and to determine their prognostic significance., Methods: Pathological reports of all colorectal cancer (CRC) patients undergoing CRS/HIPEC between 2009 and 2016 were retrospectively reviewed. Pathological specimens lacking tumor cells were defined as negative pathological specimens (NPS). The intraoperative peritoneal cancer index (PCI) and pathological PCI (excluding NPS) were calculated separately. Receiver operating characteristic (ROC) curves were applied to compare the prognostic value of intraoperative and pathological scoring systems., Results: For 108 CRC patients, 113 CRS/HIPEC procedures were performed. Of 959 pathological specimens examined, 178 (18.6%) were NPS. Overall, 78 procedures (69%) showed NPS. In 52 procedures (46%), the pathological PCI differed from the intraoperative PCI (∆PCI > 0). The ROC areas for intraoperative PCI and pathological PCI were similar in predicting 1-year overall survival (OS), 2-year OS, and 1-year disease-free survival (all p values not significant). However, for the patients with NPS, the number of positive specimens (containing tumor tissue) was superior to intraoperative PCI in predicting 2-year OS (ROC under the curve areas, 0.69 vs. 0.58, respectively; p = 0.012). In addition, a subgroup of 15 patients with a high ∆PCI (≥ 3) had a more favorable median OS than a matched group of 30 patients with similar intraoperative PCI and a ∆PCI of 0 (median survival not reached vs. 21.6 months, respectively; p = 0.05)., Conclusions: In the majority of CRC CRS/HIPEC procedures, NPS may be found. Among patients with NPS, pathological correlation may have a prognostic significance.

Background: Hartmann's reversal is a challenging surgical procedure with significant postoperative morbidity rates. Various surgical methods have been suggested to lower the risk of postoperative complications. In this study, we aimed to compare the postoperative results between open and laparoscopic techniques for Hartmann's reversal., Methods: A retrospective study of all patients who underwent Hartmann's reversal in five centers in central Israel between January 2004 and June 2015 was conducted. Medical charts were reviewed, analyzing preoperative and operative parameters and short-term postoperative outcomes., Results: 260 patients were included in the study. 76 patients were operated laparoscopically with a conversion rate of 26.3% (20 patients). No differences were found between patients operated laparoscopically and those operated in an open technique regarding gender (p = 0.785), age (61.34 vs. 62.64, p = 0.521), body mass index (26.6 vs. 26.2, p = 0.948), Charlson index score (1.79 vs. 1.95, p = 0.667), and cause for Hartmann's procedure (neoplastic vs. non-neoplastic, p = 0.644). No differences were seen in average time from the Hartmann's procedure to reversal (204.89 vs. 213.60 days, p = 0.688) and in overall complication rate (46.4 vs. 46.5%, p = 1). The Clavien-Dindo score for distinguishing between minor (0-2 score, p = 1) and major complications (3-5 score, p = 0.675) failed to demonstrate an advantage to laparoscopy, as well as to average length of stay (10.91 days in the laparoscopic group vs. 11.72 days in the open group, p = 0.529). An analysis based on the intention-to-treat with laparoscopy, including converted cases in the laparoscopic group, showed similar results, including overall complication rate (48.6 vs. 45.6%, p = 0.68) and Clavien-Dindo score in both minor (p = 0.24) and major complications (p = 0.44). Length of stay (10.92 vs. 11.81 days, p = 0.45) was also similar between the two groups., Conclusion: In this series, a laparoscopic approach to Hartmann's reversal did not offer any short-term advantage when compared to an open surgical approach.

Background: Measurement of bowel length is an essential surgical skill for laparoscopic and open gastrointestinal surgery in order to achieve favorable outcomes and avoid long-term complications. Variations in accuracy between the two surgical approaches may exist. However, only few studies have tried to assess these differences. Our aim was to assess reliability and inter-rater variability of small bowel length assessment during laparoscopy in an in vivo porcine model., Methods: This is a single-institution, double-blinded, technical assessment study in a porcine in vivo model. Fourteen participants (ten senior surgeons with >1000 laparoscopic procedures and four junior surgeons) had to assess and mark lengths of small bowel in both laparoscopic and open surgical approaches. Each participant was assigned to measure and mark specific, randomized distances (range 25-197 cm) in both laparoscopic and open approaches using color-coded vessel loops. Actual participant-marked distances were compared to the assigned distances followed by Bland-Altman plots and linear regression analysis to determine accuracy and proportional error trends. Study data were further compared to available data sets from previously published studies., Results: Laparoscopy measurements were significantly shorter than required (difference 33.8 ± 28.7 cm, P < 0.001, 95% CI 17.8-49.7). The measuring error was proportional to the length of the measured segment (63% of the required distances, IQR 58.9-79.0%, P = 0.02). At laparotomy, mean difference and standard deviation were lower (1.5 cm ± SD 15 cm) and not statistically significant (P = 0.7). Re-analysis of previously published data sets validated the observed errors in laparoscopic bowel measurement (P < 0.01)., Conclusions: Small bowel length assessment during laparoscopy is inaccurate and associated with substantial variability. There is a need to develop a standardized laparoscopic technique for measuring small bowel length which is simple, reproducible, and easy to learn.

We present two cases of recurrent progressive multifocal leukoencephalopathy (PML) in patients with long standing virally suppressed human immunodeficiency virus (HIV) and normal CD4+ T cell count who were taking stable regimens of highly active antiretroviral therapy (HAART). This has significant implications for other patients with a past history of PML, not just those with HIV but also those on medications such as natalizumab or fumarates.

Introduction: Laparoscopic surgery is widely practiced surgical technique in the modern surgical toolbox. The Veress needle insertion technique, while faster and easier, is associated with higher rates of iatrogenic complications (injury to internal organs, major blood vessels, etc.), morbidity and even mortality with a reported overall risk of 0.32% during surgical interventions. In order to increase the safety and ease of closed insertion technique, we designed and tested an improved prototype of the Veress needle., Methods: The new Veress needle includes a distal expandable portion that allows elevation of the abdominal wall and safe insertion of the first trocar over it. The needle was assessed by measurement of ease of insertion, ease of trocar advancement, associated tissue damage, device integrity and weight-bearing capacity on an ex vivo Gallus domesticus animal model: The prototype was tested over 20 times using different traction forces. The experiment was qualitatively repeated on an ex vivo porcine model., Results: In the G. domesticus model, the improved needle supported forces of up to 5.75 kg F. No damage or mechanical malfunction was seen at any stage of the experiment. Needle penetration, ease of trocar insertion, system anchoring and weight-bearing capacity were rated (1-5) by four raters--mean 4.9 ± 0.31. Inter-rater agreement was high (free marginal κ 0.75). The porcine experiment revealed similar ease of use with neither complication nor damage to the abdominal wall., Conclusions: We believe that the new Veress system is easy to use, requires no additional training, non-inferior in its capabilities compared to the traditional Veress needle, with the advantage of improving the safety of the first trocar insertion phase of the operation.

Study Objective: The objective of this study was to evaluate and compare the impact of three-dimensional (3D) imaging system on the performance of basic laparoscopic tasks in a test model by novice and experienced surgeons., Design: Three tasks were performed in a test model by 30 surgeons, 15 experienced surgeons, and 15 with minimal laparoscopic experience. The tasks were performed using 2D and 3D vision systems., Design Classification: Canadian Task Force II-1., Subjects: Fifteen experienced laparoscopic surgeons and fifteen novices with minimal laparoscopic experience., Measurements: Performance times were recorded using both two-dimensional and 3D imaging system for each task., Main Results: Performance time for all skills was significantly (P < 0.02) shorter when using 3D imaging system. Performance times were reduced by 18-31% using 3D imaging for all participants. Experienced surgeons performed the tasks faster and showed similar improvement while using 3D imaging system., Conclusion: 3D vision systems allow for significant improvement in performance times of basic laparoscopic tasks in a test model for both inexperienced and advanced laparoscopic surgeons. Experienced surgeons benefit as much as novices from 3D imaging system. This benefit should be weighed against the disadvantages of the 3D vision systems, mainly cost, decreased light, eye strain, headaches, and shorter focal lengths.

Objective: The purpose of this multimedia article is to present a technique of laparoscopic rectopexy with fixation of the rectum to the sacrum using a short strip of mesh., Methods: The technique is presented in a video clip., Results: The laparoscopic rectopexy procedure is usually performed using four ports. First, the upper rectum is mobilized on its right side, and dissection posterior to the rectum is performed all the way down to the level of the pelvic floor. Anterior mobilization is performed next, and the rectovaginal septum is dissected all the way down to the level of the pelvic floor. A short strip of mesh, approximately 5 cm × 2 cm in diameter, is introduced through the right lower quadrant port. The mesh is placed vertically on the sacrum from the level of the sacral promontory downward, and secured to the sacrum using endo-tackers, which should be applied below the promontory and adjacent to the midline to avoid injury to the hypogastric nerves. The mesorectum is then secured to the mesh in four points using absorbable sutures. Applying adequate sutures directly to the presacral fascia using the relatively small needles that can go through the ports may be a difficult task. Suturing to the mesh, however, is very easy, and in our opinion may be considered the main advantage of the posterior mesh technique. Ten female patients (age range, 26-84 years) underwent rectopexy using this technique. At a mean follow-up of 2.2 years, two had recurrent prolapse-one of which, the only patient in whom absorbable tackers were used-had in-house recurrence and refixation. Complications included one patient with mild pelvic pain, which spontaneously resolved in 3 weeks., Conclusion: The presented technique may ease fixation of the rectum to the sacrum and potentially improve results.

Fatty acid binding proteins (FABPs), are evolutionarily conserved small cytoplasmic proteins that occur in many tissue-specific types. One of their primary functions is to facilitate the clearance of the cytoplasmic matrix from free fatty acids and of other detergent-like compounds. Crystallographic studies of FABP proteins have revealed a well defined binding site located deep inside their beta-clam structure that is hardly exposed to the bulk solution. However, NMR measurements revealed that, when the protein is equilibrated with its ligands, residues that are clearly located on the outer surface of the protein do interact with the ligand. To clarify this apparent contradiction we applied molecular dynamics simulations to follow the initial steps associated with the FABP-fatty acid interaction using, as a model, the interaction of toad liver basic FABP, or chicken liver bile acid binding protein, with a physiological concentration of palmitate ions. The simulations (approximately 200 ns of accumulated time) show that fatty acid molecules interact, unevenly, with various loci on the protein surface, with the favored regions being the portal and the anti-portal domains. Random encounters with palmitate at these regions led to lasting adsorption to the surface, while encounters at the outer surface of the beta-clam were transient. Therefore, we suggest that the protein surface is capable of sequestering free fatty acids from solution, where brief encounters evolve into adsorbed states, which later mature by migration of the ligand into a more specific binding site.

The fatty acid binding proteins (FAPBs) function as intracellular carriers of fatty acid (FA) and related compounds. During the digestion of lipids, the local concentration of FA exceeds their critical micellar concentration; the excess ratio of FA/FABP can be as high as approximately 1,000/1, consequently building micelles. Considering that the micelle formation is a rapid process, the FABP must be able to remove the mini-micelle. In this study, we describe the results of molecular dynamics simulations of liver basic FABP (Lb-FABP), carried out in the presence of approximately 20 mM palmitate ions, all in the presence of explicit water and at ionic strength of approximately 100 mM, approximating physiological conditions. The Lb-FABP appears to react, along with a free FA, with mini-micelle creating a stable complex (on the time scale of the simulations), which is attached to the anti-portal domain of the protein. The complex may be formed by the stepwise addition of free FA or through the interaction of a pre-formed mini-micelle with the free protein. The driving force of the mini-micelle-FABP complex is a combination of electrostatic attraction between the negative carboxylates of the mini-micelle with the positive charge of the N terminal amine residues and Lennard-Jones FA-protein interactions. The preferred tendency of the mini-micelle to react with the anti-portal domain retains the alpha-helixes of the portal region free for its electrostatic interaction with the membrane, ensuring a rapid unloading of the cargo on the membrane.

The mechanism of proton transfer at the interface is the most prevalent reaction in the biosphere, yet its modeling at atomic level is still technically impossible. The difficulties emerge from the quantum mechanical nature of the proton, the modulation of the local electrostatic potential by the protein-water dielectric boundary and the formation of covalent bonds with proton binding sites whenever encounters take place. To circumvent some of these difficulties, and to identify the effect of the local electrostatic field, we present molecular dynamics simulations, where Na+ and Cl- ions diffuse at the surface of a small model protein, the S6 of the bacterial ribosome. The analysis reveals the presence of a detained state, where an ion is located for a relatively long period within the immediate environment of certain attractor residues. In the detained state the ion retains its ability to diffuse, yet the local field deters it from leaving to the bulk. When an ion is detained inside a Coulomb cage, it has a high probability to be transferred between nearby attractors, thus forming a mechanism similar to that responsible for the proton collecting antenna present on proton proteins.

Background: Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan was used as induction treatment in locally advanced extremity soft-tissue sarcomas for limb sparing surgery. The typical histopathological changes that occur in these tumoral masses are described in a series of 30 patients., Methods: Fresh tumor specimens of 27 high grade extensive soft-tissue sarcomas and 3 recurrent desmoid tumors of the extremities were collected 6 to 8 weeks after hyperthermic isolated limb perfusion with tumor necrosis factor-alpha plus melphalan. The specimens were studied for surgical margins, extent and type of tumor necrosis, lymph node involvement, perineural and vascular invasion, and the effects on adjacent normal tissues such as nerves, muscles, and blood vessels., Results: The typical histological changes were central cystic hemorrhagic necrosis with pericystic extensive fibrosis. Some nonspecific changes were noted in the soft tissues around the mass. In eight cases, more than 90% necrosis was found. In 17 cases, the extent of necrosis ranged between 60% and 90% (80%-90% in 4 of 17 cases). In five cases, less than 60% necrosis was noted. The best responses (>90% necrosis) were observed in distally located tumors. The responsive types were malignant fibrous histiocytoma, followed by myxoid liposarcoma and synovial sarcoma. Desmoid tumors showed less necrosis than high grade sarcomas. Vascular invasion was observed in two cases and intralesional venous thrombosis in one case. No perineural invasion or lymph nodes involvement were observed. The soft tissues adjacent to the tumor bed did not show major morphological changes. No correlation was found between the histological changes and each of the following: the anatomical (upper vs. lower limb) or compartmental location of the tumor; whether the tumor was primary or recurrent; and the types of previous treatment (systemic chemotherapy or radiotherapy) and tumor size., Conclusions: This is the first serial histological description of the effects of tumor necrosis factor-alpha and melphalan administered via hyperthermic isolated limb perfusion on the tumoral masses of limb soft-tissue sarcomas. The small number of specimens and, especially, the variability of tumors preclude definite conclusions. Larger numbers and more homogeneity are needed in future studies.

The water layers interspacing between the phospholipid membranes of a multilamellar vesicle are 3-10 water layers across and their width is adjusted by osmotic pressure (Parsegian, V.A., et al., 1986. Methods Enzymol. 127:400-416). In these thin water layers we dissolved pyranine (8 hydroxypyrene 1,3,6 trisulfonate), a compound which, upon photo excitation, ejects it hydroxy proton with time constant of 100 psec. (Gutman, M. 1986. Methods Enzymol. 127:522-538). In the present study we investigated how the width of the aqueous layer, the density of phosphomoieties on the membrane's surface and the activity of water in the layer affect the capacity of protons to diffuse out from the electrostatic cage of the excited anion before it decays to the ground state. Using a combination of steady-state and subnanosecond time-resolved fluorescence measurements we determined the average number of proton excited-anion recombinations before the proton escapes from the Coulomb cage. The probability of recombination in thin water layer is significantly higher than in bulk. The factor contributing most to enhancement of recombination is the diminished water activity of the thin aqueous layer. The time frame for proton escape from an electrostatic trap as big as a membrane-bound protein is 3 orders of magnitude shorter than turnover time of membrane-bound enzymes. Thus the effects of local forces on proton diffusion, at the time scale of physiological processes, is negligible.

The extent of the deactivation of the mitochondrial succinate dehydrogenase by oxaloacetate is a function of the redox state of the enzyme. Oxidized enzyme is deactivated by much lower concentrations of oxaloacetate than those needed to deactivate reduced enzyme. An accurate method for measuring this relationship is the redox titration of the enzymic activity of succinate dehydrogenase, carried out in the presence of oxaloacetate. For each concentration of oxaloacetate a different redox titration curve was reported with the apparent mid-potential decreasing with increasing oxaloacetate. These results are compatible with a model which proposes that both oxidized and reduced enzymes can form the catalytically non-active complex with oxaloacetate, but that the complex formed the the oxidized enzyme is more stable than that formed by the reduced enzyme. When the oxaloacetate concentration is low, reduction of the enzyme will lower the fraction of the succinate dehydrogenase-oxaloacetate complex, a reaction which we observe as reductive activation of the enzyme. If this experiment is repeated in the presence of high concentration of oxaloacetate, no activation of the enzyme takes place, but the low stability of the reduced enzyme oxaloacetate complex is revealed by the rapid exchange of the enzyme-bound oxaloacetate with the free ligand. The rate of this exchange is extremely slow at high positive potential and becomes faster upon lowering of the poise potential. The reductive activation of the succinate dehydrogenase is regarded as a two step reaction. In the first step the reduced non-active complex releases the oxaloacetate and in the second step the active form of the enzyme is evolved. These two steps can be observed experimentally; Reductive activation at a redox potential higher than the mid-potential of the oxaloacetate-malate couple (minus 166 mV) is characterized by Ea = 18 Kca/mole, the final equilibrium level of activation decreases upon lowering of the temperature. Reduction activation of the enzyme at minus 240 mV is a very rapid reaction which goes to completion at all temperatures tested and has an activation energy of 12.5 Kcal/mole. The mechanism of the reductive activation and its possible role in the regulation of succinate dehydrogenase in the mitochondria is discussed.

The oxidation of cytochrome b561 by ATP was measured in submitochondrial particles inhibited by antimycin. The redox potential of the bulk (M phase) was controlled by the ratio of fumarate:succinate, and the oxidation of cytochrome b was calculated and expressed as a change in redox potential (Eh) measured in millivolts. The oxidation of cytochrome b561 is an energy-driven reaction affected only by the delta psi component of the proton motive force. The oxidation (measured in millivolts) is a function of the phosphate potential, reaching a maximal value of 40 mV at delta G'ATP less than - 12 kcal/mole. The maximal measured value of ATP-dependent delta psi was 100 mV. Thus only a fraction of the membrane potential effects the redox state of cytochrome b561. In contrast to the ATP-induced oxidation of cytochrome b561, cytochrome b566 is in redox equilibrium with fumarate succinate either in the presence or in the absence of ATP. The selective oxidation of b561 is explained within the term of the Q cycle as a reflection of delta psi on the electron electrochemical potential. The positive electric potential of the C phase causes cytochrome b566 to act as oxidant with respect to cytochrome b561. In the presence of antimycin cytochrome b561 cannot equilibrate with the quinone and undergoes oxidation, while cytochrome b566 reequilibrates with the quinone and thus regains redox equilibrium with the fumarate succinate redox buffer.

Succinate dehydrogenase is subjected to positive and negative modulation. The negative modulators oxaloacetate and D- or L-malate transform the enzyme into a nonactive complex in which oxaloacetate is bound. The deactivation by malate involves its oxidation by the succinate dehydrogenase which then deactivates the enzyme. In the present study we measured the activity of succinate dehydrogenase in the presence of two opposing effectors,L-malate as deactivator and CoQH2 as an activator. With these opposingeffectors present, the catalytic activity of succinate dehydrogenase assumes a steady state, the level of which is a function of the concentration of the two effectors. At lowconcentration of L-malate all of the succinate dehydrogenase activity is protected by CoQH2, while at saturating malate concentrations only 60-70% of activity is protected. Kinetic analysis of the approach to the steady state indicates that the protective effect of CoQH2 is not due to its activator property but due to its ability ofreduce the enzyme. This was verified by carrying out a radox titration of succinatedehydrogenase activity in the presence of L-malate. A redox active component was characterized with E = +25 mV and n = 1.8. When this component is reduced, L-malate cannot deactivate the succinate dehydrogenase, but when in the oxidized state the enzyme is susceptible to such deactivation. It is proposed that this group participates in the regulation of the activity of succinate dehydrogenase in the mitochondria.