Two new species of Astata Latreille from Iran (Hymenoptera, Astatidae).

Two new digger wasp species of the genus Astata Latreille, 1796 (Hymenoptera, Astatidae), A. ljubomirovi sp. nov. and A. rubriventris sp. nov. are described from Iran. Moreover, A. compta Nurse is newly recorded from the Palaearctic region and Iran, redescribed and illustrated. Diagnostic characters and key features to each species are given. With the present additions, the total number of Astata recorded from Iran increases up to 14.

A review of Dinetus Panzer, 1806 with descriptions of five new species and keys to world species (Hymenoptera, Crabronidae).

A review of all known species of Dinetus Panzer, 1806 is given. Five species are described for the first time: D. arabicus sp. nov., D. deserticus sp. nov., D. jordanicus sp. nov., D. schmideggeri sp. nov. and D. vanharteni sp. nov. Separate keys for males and females of all known species are provided. The females of D. arabicus sp. nov. and D. schmideggeri sp. nov. and the males of D. cereolus Morice, 1897, D. deserticus sp. nov., D. hameri Notton, 2020, D. rakhimovi Mokrousov Khedher, 2020, D. politus Turner, 1917 and D. vanharteni sp. nov. are unknown. With this, the total number of species increases to 21. Detailed distribution data of all examined species are presented, except the widely distributed D. pictus.

Sagittal Stability and Implant Design Affect Patient Reported Outcomes After Total Knee Arthroplasty.

BACKGROUND: Joint stability is one of the goals of any joint replacement. The contribution of prosthesis design to sagittal stability in total knee arthroplasty (TKA) has emerged as an area of interest. The purpose of this study was to evaluate the sagittal stability of four prosthesis types and determine the effect on patient reported outcome measures (PROMs). METHODS: A matched-cohort cross-sectional study was performed on 60 patients after TKA at 1-year follow-up. Three surgeons performed 10 medially stabilized (MS) TKA and 10 non-MS TKA. Sagittal stability was assessed by a blinded observer using a KT-1000 arthrometer, Lachman's test, and the anterior drawer test. PROMs (Oxford, Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, Forgotten joint score) and visual analog scale assessed function and satisfaction. RESULTS: MS TKA had significantly decreased translation on KT-1000 and improved stability compared with non-MS TKA (P < .05). Increased PROMs were demonstrated in the MS TKA group compared with the non-MS TKA group (P < .05). When divided based on objective stability, regardless of the prosthesis type, patients with a stable knee had superior PROMs (P < .05), particularly in sport-related questions. CONCLUSION: The MS TKA had significantly greater sagittal stability, improved PROMs, and satisfaction compared with non-MS TKA. Independent of prosthesis design, patients with greater sagittal stability demonstrated improved PROMs.

Lysozyme, a mediator of sepsis that deposits in the systemic vasculature and kidney as a possible mechanism of acute organ dysfunction.

In septic shock (SS), dysfunction of many organ systems develops during the course of the illness, although the mechanisms are not clear. In earlier studies, we reported that lysozyme-c (Lzm-S), a protein that is released from leukocytes and macrophages, was a mediator of the myocardial depression and vasodilation that develop in a canine model of Pseudomonas aeruginosa SS. Whereas both of these effects of Lzm-S are dependent on its ability to intrinsically generate hydrogen peroxide, we subsequently showed that Lzm-S can also deposit within the vascular smooth muscle layer of the systemic arteries in this model. In the present study, we extend our previous findings. We used a canine carotid artery organ bath preparation to study the time course and dose dependence of Lzm-S deposition within the vascular smooth muscle layer. We used a human aortic vascular smooth muscle cell preparation to determine whether Lzm-S can persistently inhibit contraction in this preparation. We also used a canine P. aeruginosa model to determine whether Lzm-S deposition might occur in other organs such as the kidney, liver, and small intestine. The results showed that, in the carotid artery organ bath preparation, Lzm-S deposition occurred within minutes of instillation and there was a dose-response effect. In the human aortic vascular smooth muscle cell preparation, Lzm-S inhibited contraction during a 4-day period. In the in vivo model, Lzm-S accumulated in the kidney and the superior mesenteric artery. In a canine renal epithelial preparation, we further showed that Lzm-S can be taken up by the renal tubules to activate inflammatory pathways. We conclude that Lzm-S can deposit in the systemic vasculature and kidneys in SS, where this deposition could lead to acute organ dysfunction.

Triazacyclophane (TAC)-scaffolded histidine and aspartic acid residues as mimics of non-heme metalloenzyme active sites.

We describe the synthesis and coordination behaviour to copper(II) of two close structural triazacyclophane-based mimics of two often encountered aspartic acid and histidine containing metalloenzyme active sites. Coordination of these mimics to copper(I) and their reaction with molecular oxygen leads to the formation of dimeric bis(µ-hydroxo) dicopper(II) complexes.

Mechanisms of systemic vasodilation by lysozyme-c in septic shock.

In septic shock (SS), cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme-c (Lzm-S), released from leukocytes, contributed to systemic vasodilation in a canine model of SS. We then delineated the pathway by which this occurs in a canine carotid artery organ bath preparation (CAP). We showed that Lzm-S could intrinsically generate hydrogen peroxide (H(2)O(2)) and that H(2)O(2) subsequently reacted with endogenous catalase to form compound I, an oxidized form of catalase. In turn, compound I led to an increase in cyclic guanosine 3',5'-monophosphate to produce vasodilation. However, it was not clear from previous studies whether it is necessary for Lzm-S to bind to the vasculature to cause vasodilation or, alternatively, whether the generation of H(2)O(2) by Lzm-S in the surrounding medium is all that is required. We examined this question in the present study in which we used multiple preparations. In a partitioned CAP, we found that when we added Lzm-S to a partitioned space in which a semipermeable membrane prevented diffusion of Lzm-S to the carotid artery tissue, vasodilation still occurred because of diffusion of H(2)O(2). On the other hand, we found that Lzm-S could accumulate within the vascular smooth muscle layer (VSML) after 7 h of SS in a canine model. We also determined that when Lzm-S was located in close proximity to vascular smooth muscle cells, it could generate H(2)O(2) to produce lengthening in a human cell culture preparation. We conclude that there are two mechanisms by which Lzm-S can cause vasodilation in SS. In one instance, H(2)O(2) generated by Lzm-S in plasma diffuses to the VSML to cause vasodilation. In a second mechanism, Lzm-S directly binds to the VSML, where it generates H(2)O(2) to produce vasodilation.

Benefits of ethyl gallate versus norepinephrine in the treatment of cardiovascular collapse in Pseudomonas aeruginosa septic shock in dogs.

INTERVENTIONS: Vasopressor therapy is required in septic shock to maintain tissue perfusion in the face of hypotension. Unfortunately, there are significant side effects of current vasopressors, and newer agents need to be developed. We recently discovered that ethyl gallate, a nonflavonoid phenolic antioxidant found in food substances, could reverse low mean arterial pressure found in an experimental model of septic shock due to inhibition of hydrogen peroxide signaling. In the present study, we compared the hemodynamic and biochemical effects of ethyl gallate vs. those of the commonly used vasopressor, norepinephrine, in a bacteremic canine model of Pseudomonas aeruginosa sepsis in two protocols. MEASUREMENTS AND MAIN RESULTS: We performed these studies in anesthetized and mechanically ventilated dogs. In the early treatment protocol, we infused P. aeruginosa until mean arterial pressure first decreased to ∼60 mm Hg (about 2-3 hrs), after which we stopped the infusion and randomly administered ethyl gallate or norepinephrine in respective groups. In the late treatment protocol, we administered ethyl gallate or norepinephrine after a sustained ∼5-hr decrease in mean arterial pressure to 60 mm Hg and continued the infusion for the duration of the experiment. We followed parameters for over 10 hrs after the initiation of P. aeruginosa in both groups. We measured stroke work, urine output, serum creatinine, among other parameters, and used serum troponin T as an index of myocardial injury. We found that in both protocols, ethyl gallate and norepinephrine improved mean arterial pressure and stroke work to similar extents over the duration of the study. Particularly in the late treatment protocol, ethyl gallate resulted in a lower heart rate, a lower troponin T, and a greater urine output as compared with norepinephrine (p < .05). CONCLUSIONS: These results suggest that phenolic antioxidants, such as ethyl gallate, that inhibit hydrogen peroxide signaling, may represent an alternative class of vasopressors for use in septic shock.

Ethyl gallate, a scavenger of hydrogen peroxide that inhibits lysozyme-induced hydrogen peroxide signaling in vitro, reverses hypotension in canine septic shock.

Although hydrogen peroxide (H2O2) is a well-described reactive oxygen species that is known for its cytotoxic effects and associated tissue injury, H2O2 has recently been established as an important signaling molecule. We previously demonstrated that lysozyme (Lzm-S), a mediator of sepsis that is released from leukocytes, could produce vasodilation in a phenylephrine-constricted carotid artery preparation by H2O2 signaling. We found that Lzm-S could intrinsically generate H2O2 and that this generation activated H2O2-dependent pathways. In the present study, we used this carotid artery preparation as a bioassay to define those antioxidants that could inhibit Lzm-S's vasodilatory effect. We then determined whether this antioxidant could reverse the hypotension that developed in an Escherichia coli bacteremic model. Of the many antioxidants tested, we found that ethyl gallate (EG), a nonflavonoid phenolic compound, was favorable in inhibiting Lzm-S-induced vasodilation. In our E. coli model, we found that EG reversed the hypotension that developed in this model and attenuated end-organ dysfunction. By fluorometric H2O2 assay and electrochemical probe techniques, we showed that EG could scavenge H2O2 and that it could reduce H2O2 production in model systems. These results show that EG, an antioxidant that was found to scavenge H2O2 in vitro, was able to attenuate cardiovascular dysfunction in a canine in vivo preparation. Antioxidants such as EG may be useful in the treatment of hemodynamic deterioration in septic shock.

Lysozyme, a mediator of sepsis that intrinsically generates hydrogen peroxide to cause cardiovascular dysfunction.

In septic shock, cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme (Lzm-S), released from leukocytes, contributed to the myocardial depression and arterial vasodilation that develop in canine models of septic shock. To cause vasodilation, Lzm-S generates hydrogen peroxide (H(2)O(2)) that activates the smooth muscle soluble guanylate cyclase (sGC) pathway, although the mechanism of H(2)O(2) generation is not known. To cause myocardial depression, Lzm-S binds to the endocardial endothelium, resulting in the formation of nitric oxide (NO) and subsequent activation of myocardial sGC, although the initial signaling event is not clear. In this study, we examined whether the myocardial depression produced by Lzm-S was also caused by the generation of H(2)O(2) and whether Lzm-S could intrinsically generate H(2)O(2) as has been described for other protein types. In a canine ventricular trabecular preparation, we found that the peroxidizing agent Aspergillus niger catalase, that would breakdown H(2)O(2), prevented Lzm-S- induced decrease in contraction. We also found that compound I, a species of catalase formed during H(2)O(2) metabolism, could contribute to the NO generation caused by Lzm-S. In tissue-free experiments, we used a fluorometric assay (Ultra Amplex red H(2)O(2) assay) and electrochemical sensor techniques, respectively, to measure H(2)O(2) generation. We found that Lzm-S could generate H(2)O(2) and, furthermore, that this generation could be attenuated by the singlet oxygen quencher sodium azide. This study shows that Lzm-S, a mediator of sepsis, is able to intrinsically generate H(2)O(2). Moreover, this generation may activate H(2)O(2)-dependent pathways leading to cardiovascular collapse in septic shock.

Dental therapy before and after radiotherapy--an evaluation on patients with head and neck malignancies.

The present investigation evaluates the dental care situation of patients with head and neck cancer before and after radiotherapy. The situations of these patients in 1993 and 2005 were compared to detect similarities, differences and developments. In the years 1993 and 2005, 37 and 36 patients, respectively, with head and neck cancer treated by the local departments of otorhinolaryngology and of radiotherapy were examined consecutively according to their aftercare appointments. Time points of radiotherapy treatment of the patients evaluated in 1993 varied from 1984 to 1993. The patients evaluated in 2005 had received radiotherapy between 1998 and 2005. Therefore the applied radiotherapeutic regimen differed not only between the two groups of patients, but also within each group. The information for these investigations was provided anonymously. It was evaluated with descriptive statistics. The evaluation of the data shows distinct differences with respect to preventive and therapeutic dental care measures. In 2005, 35 out of 36 patients (97.2%) had a dental consultation before radiotherapy (1993, 65%). All 27 dentate patients (100%) obtained a splint for fluoride application (1993, none). 29% fewer edentulous patients were seen than in 1993. The number of teeth destroyed decreased from 19.2% (1993) to 7.8% in 2005. Mycoses due to Candida spp. and chronic failures in wound healing were rare (5.5%). In the course of the 12 years, prophylactic measures, such as the application of splints for fluoride treatment, were intensified. However, concepts for the dental care of patients undergoing radiotherapy, especially following the radiation, should be widened to avoid ruined teeth and long delayed wound healings.

Lysozyme, a mediator of sepsis that produces vasodilation by hydrogen peroxide signaling in an arterial preparation.

In septic shock, systemic vasodilation and myocardial depression contribute to the systemic hypotension observed. Both components can be attributed to the effects of mediators that are released as part of the inflammatory response. We previously found that lysozyme (Lzm-S), released from leukocytes, contributed to the myocardial depression that develops in a canine model of septic shock. Lzm-S binds to the endocardial endothelium, resulting in the production of nitric oxide (NO), which, in turn, activates the myocardial soluble guanylate cyclase (sGC) pathway. In the present study, we determined whether Lzm-S might also play a role in the systemic vasodilation that occurs in septic shock. In a phenylephrine-contracted canine carotid artery ring preparation, we found that both canine and human Lzm-S, at concentrations similar to those found in sepsis, produced vasorelaxation. This decrease in force could not be prevented by inhibitors of NO synthase, prostaglandin synthesis, or potassium channel inhibitors and was not dependent on the presence of the vascular endothelium. However, inhibitors of the sGC pathway prevented the vasodilatory activity of Lzm-S. In addition, Aspergillus niger catalase, which breaks down H(2)O(2), as well as hydroxyl radical scavengers, which included hydroquinone and mannitol, prevented the effect of Lzm-S. Electrochemical sensors corroborated that Lzm-S caused H(2)O(2) release from the carotid artery preparation. In conclusion, these results support the notion that when Lzm-S interacts with the arterial vasculature, this interaction results in the formation of H(2)O(2), which, in turn, activates the sGC pathway to cause relaxation. Lzm-S may contribute to the vasodilation that occurs in septic shock.

Preoperative sterilization and disinfection of drill guide templates.

The aim of the in vitro study was to evaluate the decontamination potential of common antiseptic solutions for heat-sensitive implantological drill guide templates. One hundred implantologists were evaluated on the basis of a questionnaire for their measures of disinfection. On the basis of these results, 80% alcohol, Octenidine 0.1%, and Chlorhexidine 0.12% were tested in an in vitro model for their decontamination efficacy for heat-sensitive plastic material infected with Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Enterobacter cloacae, Escherichia coli, and Candida albicans. The microorganisms were selected on the basis of results of environmental testing of dental laboratories. The results of the questionnaire revealed that Chlorhexidine was used by 30%, 80% alcohol by 23%, and Octenidine by 7% of the dentists. Using the in vitro model, with the exception of S. aureus, Chlorhexidine was not able to completely eliminate the microorganisms after 15 min of application. In contrast, the treatment with Octenidine revealed no further growth of the tested microorganisms after that time. The 80% alcohol was more efficient. No growth of microorganisms could be detected in any of the tests after 5 min of incubation. On the basis of our results and due to the fact that suitable installations for sterilization were hardly used by the dental practitioners, the disinfection of templates should be preferentially performed with 80% alcohol or Octenidine using an incubation time of 15 min with ultrasonication.

N,N'-diacetylchitobiose, an inhibitor of lysozyme, reverses myocardial depression and lessens norepinephrine requirements in Escherichia coli sepsis in dogs.

Cardiovascular dysfunction in septic shock (SS) is ascribed to the release of inflammatory mediators. Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. This effect can be blocked in an in vitro preparation by chitobiose, a competitive inhibitor of Lzm-S. In the present study, we examined whether chitobiose treatment can reverse myocardial depression and obviate NE requirements in two respective canine E. coli preparations. In a 6-h study, we administered chitobiose after 3.5 h of E. coli bacteremia and compared stroke work (SW) and MAP at 6 h with a sepsis control group. In a 12-h study, we determined whether chitobiose treatment can reduce the need for NE requirements during 12 h of bacteremia. In the latter study, either chitobiose or NE was given when MAP decreased approximately 20% from the presepsis value in respective groups. In anesthetized, mechanically ventilated dogs, we monitored hemodynamic parameters during continuous E. coli infusion. In the 6-h study, chitobiose improved SW and MAP at the 6-h period as compared with the nontreated sepsis group. In the 12-h study, SW and MAP increased after chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.

Lysozyme, a mediator of sepsis, impairs the cardiac neural adrenergic response by nonendothelial release of NO and inhibitory G protein signaling.

We previously showed that lysozyme (Lzm-S), derived from leukocytes, caused myocardial depression in canine sepsis by binding to the endocardial endothelium to release nitric oxide (NO). NO then diffuses to adjacent myocytes to activate the cGMP pathway. In a canine right ventricular trabecular (RVT) preparation, Lzm-S also decreased the inotropic response to field stimulation (FSR) during which the sympathetic and parasympathetic nerves were simulated to measure the adrenergic response. In the present study, we determined whether the pathway by which Lzm-S decreased FSR was different from the pathway by which Lzm-S reduced steady-state (SS) contraction. Furthermore, we determined whether the decrease in FSR was due to a decrease in sympathetic stimulation or enhanced parasympathetic signaling. In the RVT preparation, we found that the inhibitory effect of Lzm-S on FSR was prevented by NO synthase (NOS) inhibitors. A cGMP inhibitor also blocked the depressant activity of Lzm-S. However, in contrast to the Lzm-S-induced decline in SS contraction, chemical removal of the endocardial endothelium by Triton X-100 to eliminate endothelial NO release did not prevent the decrease in FSR. An inhibitory G protein was involved in the effect of Lzm-S, since FSR could be restored by treatment with pertussis toxin. Atropine prevented the Lzm-S-induced decline in FSR, whereas beta(1)- and beta(2)-adrenoceptor function was not impaired by Lzm-S. These results indicate that the Lzm-S-induced decrease in FSR results from a nonendothelial release of NO. NO then acts through inhibitory G protein to enhance parasympathetic signaling.

Decontamination of rough titanium surfaces with diode lasers: microbiological findings on in vivo grown biofilms.

OBJECTIVES: The bactericidal efficacy of diode lasers has already been demonstrated in vitro. We investigated the reduction of aerobe bacteria - colonizing rough titanium samples in biofilms intraorally grown - by diode lasers of different wave lengths. MATERIAL AND METHODS: Twenty-two volunteers participated in the trial. They were fitted for 10 days with custom-made intraoral plastic splints carrying titanium sleeves. A part of the sleeves was then irradiated with diode lasers in different modes. The other part remained non-irradiated and served as control. Directly after irradiation, the sleeves were swabbed and the gained bacteria were first examined microscopically and then were cultured under aerobic conditions. RESULTS: The bacteria in the controls and in the treated samples were quantified. A comparison with the controls revealed a marked overall reduction of bacterial colonization in all irradiated sleeves. Continuous irradiation for 20 s reduced bacteria counts by 99.67% at 810 nm and 99.58% at 980 nm. Repeating the 20 s exposure five times reduced counts by 99.98% at 810 nm and by 99.39% at 980 nm. A 98.86% reduction was seen after irradiation in pulsed mode. A further analysis in respect of different isolated bacteria revealed that the streptococci group was reduced by 99.29-99.99%, while the staphylococci group was reduced to a lesser extent in the range 94.67-99.99%. CONCLUSION: The results are of clinical relevance. In comparison with the mean bacterial counts of the untreated samples, all irradiation programs studied in this investigation reduced mean bacterial colonization in a biofilm on intraoral rough titanium surfaces by more than 98%. The actual extent of reduction was dependent on the bacteria species as well as on the irradiation mode.

Traumatic injuries to the primary dentition and effects on the permanent successors - a clinical follow-up study.

This study investigated problems in the permanent dentition that, according to history and records, were attributable to dental alveolar injuries of the primary dentition. 106 children have been involved in the study, who had experienced primary anterior tooth trauma affecting a total of 200 teeth. Thirty-nine patients (81 teeth) were available for follow-up examinations. In 25% of the cases followed up, damage was found on the successors in the secondary dentition (16 children/20 teeth). In half of the cases, a comparatively mild form of lesion like enamel discoloration was observed. This was the result of an injury during the tooth maturation process causing enamel hypoplasia. Clinically more relevant were the dental deformities: cessation of root formation or retention caused by ankylosis, which made up the remaining 50% of cases. This was confirmed by clinical long-term observation. The different effects on the permanent teeth can only be detected by radiography after an interval of several months or may even be clinically assessed only after the eruption of the clinical crown.

Efficient microwave-assisted synthesis of multivalent dendrimeric peptides using cycloaddition reaction (click) chemistry.

Multivalent dendrimeric peptides were synthesized via a microwave-assisted Huisgen 1,3-dipolar cycloaddition between azido peptides and dendrimeric alkynes in yields ranging from 46 to 96%.

Lysozyme binding to endocardial endothelium mediates myocardial depression by the nitric oxide guanosine 3',5' monophosphate pathway in sepsis.

Inflammatory mediators have been implicated as a cause of reversible myocardial depression in septic shock. We previously reported that the release of lysozyme-c (Lmz-S) from leukocytes from the spleen or other organs contributes to myocardial dysfunction in Escherichia coli septic shock in dogs by binding to a cardiac membrane glycoprotein. However, the mechanism by which Lzm-S causes this depression has not been elucidated. In the present study, we tested the hypothesis that the binding of Lzm-S to a membrane glycoprotein causes myocardial depression by the formation of nitric oxide (NO). NO generation then activates soluble guanylyl cyclase and increases cyclic guanosine monophosphate (cGMP), which in turn triggers contractile impairment via activation of cGMP-dependent protein kinase (PKG). We examined these possibilities in a right ventricular trabecular preparation in which isometric contraction was used to measure cardiac contractility. We found that Lzm-S's depressant effect could be prevented by the non-specific NO synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). A guanylyl cyclase inhibitor (ODQ) and a PKG inhibitor (Rp-8-Br-cGMP) also attenuated Lzm-S's depressant effect as did chemical denudation of the endocardial endothelium (EE) with Triton X-100 (0.5%). In EE tissue, we further showed that Lzm-S caused NO release with use of 4,5 diaminofluorescein, a fluorescent dye that binds to NO. The present study shows that the binding of Lzm-S to EE generates NO, and that NO then activates the myocardial guanosine 3',5' monophosphate pathway leading to cardiac depression in sepsis.

Characterization of membrane N-glycan binding sites of lysozyme for cardiac depression in sepsis.

PURPOSE: In sepsis, reversible myocardial depression has been ascribed to the release of mediators of inflammation. We previously found that lysozyme released from leukocytes from the spleen and other organs mediated myocardial depression in an Escherichia coli model of septic shock in dogs. We hypothesize that lysozyme binds to or cleaves a cardiac surface membrane N-glycoprotein to cause depression. The objectives of the present study were: 1) to determine whether the binding of lysozyme is reversible; 2) to assess the N-glycan structure to which lysozyme binds; 3) to examine whether nonenzymatic proteins, termed lectins, with a binding specificity similar to that of lysozyme could also cause depression; and 4) to assess whether the membrane to which lysozyme binds is affected by the enzymes protease type XIV and collagenase A, that are used to prepare single cell myocyte experiments. METHODS: We measured isometric contraction in a right ventricular trabecular preparation. RESULTS: We found that lysozyme binds in a reversible manner to the Man beta(1-4) GlcNAc beta(1-4)GlcNAc moiety in the tri-mannosyl core structure of high mannose/hybrid and tri-antennary carbohydrate classes where GlcNAc is N-acetylglucosamine and Man is mannose. Lectins with a specificity similar to that of lysozyme also caused depression, and lysozyme's depressant activity was eliminated by protease type XIV and collagenase A. CONCLUSIONS: These results indicate that lysozyme reversibly binds to a membrane glycoprotein to cause myocardial depression in sepsis. We further localize its binding site to a variant of the chitotriose structure in the tri-mannosyl core of the membrane glycoprotein.

N,N',N"-triacetylglucosamine, an inhibitor of lysozyme, prevents myocardial depression in Escherichia coli sepsis in dogs.

OBJECTIVE: Reversible myocardial depression in sepsis has been ascribed to the release of inflammatory mediators. We recently found that lysozyme c (Lzm-S), consistent with that originating from the spleen, was a mediator of myocardial depression in an Escherichia coli model of septic shock in dogs. We further showed in a right ventricular trabecular (RVT) preparation that Lzm-S's depressant activity could be blocked by N,N',N" triacetylglucosamine (TAC), a competitive inhibitor of Lzm-S. We hypothesized that Lzm-S binds to or cleaves a cardiac membrane glycoprotein, thereby interfering with myocardial contraction in sepsis. In the present study, we examined whether TAC could prevent myocardial depression in an in vivo preparation and whether other related N-acetylglucosamine (NAG) structures could also inhibit Lzm-S's effect in RVT. DESIGN: Randomized experimental study. SETTING: University laboratory. SUBJECTS: Anesthetized, mechanically ventilated dogs. INTERVENTIONS: We produced sepsis by infusion of E. coli over an approximately 6-hr period. MEASUREMENTS AND MAIN RESULTS: We examined the effect of TAC on stroke work, our primary index of myocardial function, when treatment was administered before sepsis (pretreatment) and after 1.5 hrs (early treatment study) and 3.5 hrs of sepsis (late treatment study; LTS). In the pretreatment study and early treatment study, myocardial depression would have not yet occurred but would have already been present in the late treatment study. In RVT, we assessed the effect of other NAG oligosaccharides and variants to the NAG structure on Lzm-S's depressant activity. In pretreatment and the early treatment study, TAC prevented the reduction in stroke work observed in nontreated septic groups but did not reverse the reduction found in the late treatment study. In RVT, of the compounds tested, only N,N'-diacetylglucosamine showed an inhibitory effect. CONCLUSIONS: We found that TAC, a competitive inhibitor of Lzm-S, prevented myocardial depression in experimental sepsis. Only specific NAG structures are inhibitory to Lzm-S's depressant activity. TAC may be useful in attenuating cardiovascular collapse in sepsis.