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There are high amounts of hydrogen sulfide in deep periodontal pockets. This volatile sulfur compound may be formed from L-cysteine, hut only low levels of this amino acid can be expected to be present in periodontal pockets. Glutathione, L-γ-glutamyl-L-cysteinylglycine, is in high concentration in most tissue cells, and this tripeptide may be more readily available as a source of hydrogen sulfide formation in the pockets. The ability of 37 different species of oral bacteria to utilize glutathione iii hydrogen sulfide formation was studied. Of these species, only 2 species of Peptostrepiococcus and 5 species of Fusobacterium formed high amounts of hydrogen sulfide from glutathione within 24 h. Since the initial rate of hydrogen sulfide formation was more than 5 times higher in Peptostreptococcus micros than in any of the other bacterial species, the kinetics of sulfide formation from glutathione by P. micros was further elucidated. The formation of sulfide followed quite closely hyperbolic Michaelis-Menten kinetics. The maximal initial rate of sulfide formation (Vmax) was 163±2 nmol sulfide per minute per milligram of cellular protein. Half maximal initial rate (Km) was obtained at 7.4±0.8 μM glutathione. The initial rate of sulfide formation from L-cysteine was much slower and was almost proportional to L-cysteine concentration. This difference in kinetics of sulfide formation between glutathione and L-cysteine strongly suggested that glutathione was actively transported into the cell, whereas the transport of L-cysteine was more or less controlled by diffusion. The sulfide formation from the dipeptide L-cysteinylglycine also followed quite closely hyperbolic Michaclis-Menten kinetics. The maximal initial rate of sulfide formation (Vmax) from L-cysteinylglycine was 75 ± 2 nmol sulfide per minute per milligram of cellular protein. [ABSTRACT FROM AUTHOR]

Polymorphonuclear leukocytes are important in the defense against the anaerobic microflora of infected gingival pockets. One part of this defense is release of antibacterial granule products by polymorphonuclear leukocytes into the pockets. The aim of the present study was to compare the efficiency of polymorphonuclear leukocytes in releasing granule products under aerobic and anaerobic conditions. Polymorphonuclear leukocytes were exposed to serum-opsonized zymosan under aerobic and anaerobic conditions. The levels of released granule products were determined by combining measurements of activity with enzyme-linked immunosorbent assays. The level of released elastase was twice as high in anaerobic as in aerobic reaction mixtures. A similar difference was not detected for myeloperoxidase. However, myeloperoxidase was inactivated after its release under aerobic conditions. The release of lactoferrin was as efficient under aerobic as under anaerobic conditions. The effect of aerobic conditions on the release of elastase and the inactivation of myeloperoxidase could be ascribed to oxidants formed in the myeloperoxidase-H2O2-chloride system. Also, the activity of the released cytoplasmic enzyme lactate dehydrogenase was inactivated by oxidants formed in the myeloperoxidase-H2O2-chloride system. These findings suggest that, in the anaerobic environment of the gingival pocket, elastase and possibly also other azurophilic granule products are released in higher amounts than under fully oxygenated conditions. In this environment, the released products may also escape inactivation by the myeloperoxidase-H2O2-chloride system. [ABSTRACT FROM AUTHOR]

The concentration of urea was measured in bulk milk samples taken on seven occasions during a period of 13 months from 1,658-1,815 of the 2,100 suppliers of milk to a dairy. The mean concentration of urea was significantly higher when the cows were grazing than when they were housed, but there were no significant variations within either of these periods. In herds with very low milk urea concentrations while they were housed (< 2.4 mmol/l) the mean increase during the grazing season was approximately 2.0 mmol/l, whereas in herds with very high urea concentrations while they were housed (> 6.0 mmol/l) there was a slight decrease in urea concentration during the grazing season. The annual milk yield of herds with low urea concentrations was significantly lower than the yield of herds with intermediate or high concentrations. The interval between calving and first insemination was significantly longer in herds with low milk urea concentrations, but these herds also had a higher 56-day non-return rate. [ABSTRACT FROM AUTHOR]

One hundred and ninety three pairs of cows were selected from 38 herds, and the numbers of each pair were assigned at random to experimental and control groups. Each control cow was fed according to its yield with the feedstuffs normally used by the herd. Each experimental cow was fed in the same way and, in addition, received 500 g of a feed additive twice daily from the 40th day of lactation until first insemination or to the 75th day of lactation if no visible oestrus had been observed between days 40 and 75. One kg of the feed additive contained glucogenic substances (glycerol and Ca-propionate) equivalent to 1.90 moles of glucose, 13.6 MJ metabolizable energy, and 180 g digestible crude protein. There were no significant differences between the groups with respect to their mean daily milk yield, their plasma glucose concentrations at first insemination, or the interval between calving and first insemination. However, the experimental cows had a significantly shorter interval between calving and last insemination (mean difference 11.0 days). The pregnancy rate was significantly higher among cows with high than among cows with low plasma glucose concentrations. There was also a tendency towards a reduced pregnancy rate among cows with either high (> 7.0 mmol/litre) or low (< 4.0 mmol/litre) milk urea concentrations. [ABSTRACT FROM AUTHOR]

In polymicrobial infections such as periodontal disease, the polymorphonuclear leukocytes (PMN) may have to work in the absence of oxygen and in the presence of significant levels of hydrogen sulfide. There arc conflicting results reported on the chemotactic capacity of PMN under anaerobic conditions. It is not known whether PMN are able to migrate and release the contents of their granules in the presence of sulfide. PMN were exposed to various levels of sulfide and their chemotaxis and degranulation were studied when they were stimulated with N- formyl-methionyl-leucyl-phenylalanine or zymosan-activated serum. Chemotaxis was evaluated with the agarose method. The release of granule markers, lactoferrin and myeloperoxidase, was evaluated with enzyme-linked immunosorbent assay. PMN had similar capacity for chemotaxis under aerobic and anaerobic conditions. The migration of PMN was only to a minor extent inhibited by 1-2 mM sulfide. The release of lactoferrin and myeloperoxidase was the same under aerobic and anaerobic conditions and was not significantly influenced by sulfide. PMN seem to be very well suited to defend the tissue against bacteria under the harsh conditions prevailing in the periodontal pocket. [ABSTRACT FROM AUTHOR]

Strains of black-pigmented Bacteroides were examined for their ability to degrade collagen, albumin and benzoyl-D-L-arginine-p-nitranilide (BAPNA). B. gingivalis was the only species that showed activity against collagen and BAPNA. This activity was cell-bound, stabilized by dithiothreitol and inhibited by sulphydryl-modifying reagents such as mercuric, cupric and zinc ions, 5.5'-dithiobis- 2-nitrobenzoic acid, p-chloromercuriphenylsulfonic acid and hydrogen peroxide. The activity was also inhibited by the chelating agents EDTA and EGTA. This indicated that B. gingivalis has cell-bound thiol proteinase activity dependent on metal ions. [ABSTRACT FROM AUTHOR]

Background: The ICD-11 proposes fundamental changes to the PTSD diagnostic criteria, prompting thorough validation. While this is ideally carried out based on diagnostic interviews, most-and in the case of transcultural psychiatry all-studies have relied on self-reported measures. In this study, we used the International Trauma Interview (ITI) to assess the factor structure of ICD-11 PTSD symptoms in a sample of trauma-affected refugees., Method: The ITI was administered with a sample of refugees (n = 198), originating mainly from the Greater Middle East. The symptom ratings were subjected to a confirmatory factor analysis (CFA), comparing the ICD-11 concordant three-factor model with alternative two- and one-factor models., Results: The overall fit was adequate for both the two- and three-factor models, but favored the two-factor model. Results for both models indicated local misspecifications and that item 5, hypervigilance, displayed a suboptimal loading., Conclusion: The results generally support the use of the ITI in a severely trauma-affected refugee population, albeit with particular attention needed in the administration of item 5. The superior fit of a two-factor model warrants further testing across populations., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

HER2 (human epidermal-growth-factor receptor-2; ErbB2) and EGFR (epidermal-growth-factor receptor) are overexpressed in various forms of cancer, and the co-expression of both HER2 and EGFR has been reported in a number of studies. The simultaneous targeting of HER2 and EGFR has been discussed as a strategy with which to potentially increase efficiency and selectivity in molecular imaging and therapy of certain cancers. In an effort to generate a molecule capable of bispecifically targeting HER2 and EGFR, a gene fragment encoding a bivalent HER2-binding affibody molecule was genetically fused in-frame with a bivalent EGFR-binding affibody molecule via a (G4S)3 [(Gly4-Ser)3]-encoding gene fragment. The encoded 30 kDa affibody construct (ZHER2)2-(G4S)3-(ZEGFR)2, with potential for bs (bispecific) binding to HER2 and EGFR, was expressed in Escherichia coli and characterized in terms of its binding capabilities. The retained ability to bind HER2 and EGFR separately was demonstrated using both biosensor technology and flow-cytometric analysis, the latter using HER2- and EGFR-overexpressing cells. Furthermore, simultaneous binding to HER2 and EGFR was demonstrated in: (i) a sandwich format employing real-time biospecific interaction analysis where the bs affibody molecule bound immobilized EGFR and soluble HER2; (ii) immunofluorescence microscopy, where the bs affibody molecule bound EGFR-overexpressing cells and soluble HER2; and (iii) a cell-cell interaction analysis where the bs affibody molecule bound HER2-overexpressing SKBR-3 cells and EGFR-overexpressing A-431 cells. This is, to our knowledge, the first reported bs affinity protein with potential ability for the simultaneous targeting of HER2 and EGFR. The potential future use of this and similar constructs, capable of bs targeting of receptors to increase the efficacy and selectivity in imaging and therapy, is discussed.

Background/aim: Within the first days of life infants can already recognize their mother. This ability is based on several sensory mechanisms and increases during the first year of life, having its most crucial phase between 6 and 9 months when cortical circuits develop. The underlying cortical structures that are involved in this process are still unknown. Herein we report how the prefrontal cortices of healthy 6- to 9-month-old infants react to the sight of their mother's faces compared to that of an unknown female face., Methods: Concentrations of oxygenated haemoglobin [HbO2] and deoxygenated haemoglobin [HHb] were measured using near infrared spectroscopy (NIRS) in both fronto-temporal and occipital areas on the right side during the exposure to maternal and unfamiliar faces., Results: The infants exhibited a distinct and significantly higher activation-related haemodynamic response in the right fronto-temporal cortex following exposure to the image of their mother's face, [HbO2] (0.75 micromol/L, p < 0.001), as compared to that of an unknown face (0.25 micromol/L, p < 0.001)., Conclusion: Event-related haemodynamic changes, suggesting cortical activation, in response to the sight of human faces were detected in 6- to 9-month old children. The right fronto-temporal cortex appears to be involved in face recognition processes at this age.

When proteins containing disulphide groups were oxidized with magnesium monoperoxyphthalate at acidic pH, they acquired the property of binding thiol compounds. This was the case with the insoluble protein keratin, chosen for having a large number of disulphide bridges, and with soluble ones like BSA and immunoglobulins. The potential applications of some of these modified proteins for the preparation of soluble bioconjugates have been explored. As a particular example of an application, the immobilization of activated IgG on to solid phases might provide a new way for preparing immunoadsorbents.

We recently studied the utilization of glutathione (L-gamma-glutamyl-L-cysteinylglycine), L-cysteinylglycine and L-cysteine by anaerobic bacteria. The rate of hydrogen sulfide formation from these compounds was determined and it was concluded that Peptostreptococcus micros and Fusobacterium nucleatum subsp. nucleatum had an active transport of small peptides. In the present study it is shown that methyl mercaptan formation from L-methionine and L-methionyl-containing peptides can also be used to study peptide utilization. There were differences among the periodontal bacteria P. micros, F. nucleatum subsp. nucleatum, and Porphyromonas gingivalis in their capacity to use L-cysteine and L-methionine and peptides containing these amino acids. The peptides were used more efficiently by P. micros and F. nucleatum subsp. nucleatum than by P. gingivalis. All three species used the peptides more efficiently than the free amino acids. The efficiency in utilizing various amino acids and peptides may be among the key determinants of the periodontal microbial ecology.

In a previous population-based study of 3896 7-9-year-old children living in Sweden, it was found that 32 children (0.8%) exhibited radiographic, periodontal bone loss at > or = 2 proximal surfaces of their deciduous teeth. In the present study, 26 of the 32 children were subjected to additional oral and systemic health examination. 20 other children without any radiographic evidence of bone loss in their primary dentition served as referents. None of the cases or the referents were detected to have any systemic disease. The frequency of bleeding and suppuration on probing, radiographic proximal calculus and probing attachment loss was higher among the cases than the referents. Actinobacillus actinomycetemcomitants was found subgingivally in 14 of the cases but in none of the referents. 11 of 22 cases analysed for presence of serum antibodies against A. actinomycetemcomitans leukotoxin were sero-positive compared to none of 7 referents available for analysis. Evaluation of the data from each child revealed wide variations in clinical parameters among the children in the case group. In this group, there were children with deep probing depths, probing attachment loss, suppuration on probing, proximal calculus and presence of subgingival A. actinomycetemcomitans, indicating current periodontitis. However, in the case group there were also children without positive signs of inflammatory disease, similar to the children in the reference group. In fact, the findings suggest that less than half of the number of individuals with > or = 2 proximal sites with bone loss had current periodontitis.

Anaerobic microorganisms in periodontal pockets produce toxic amounts of hydrogen sulfide. The capacity of polymorphonuclear leukocytes to kill a capsulated and a non-capsulated variant of a group B streptococcal strain was studied in presence and absence of sulfide. The killing was equally efficient under aerobic and anaerobic conditions. However, in presence of sulfide the killing of the capsulated variant of the strain was significantly inhibited. Since this strain required higher serum concentrations to be killed by the polymorphonuclear leukocytes, it suggested that sulfide interfered with the opsonization of the bacteria. The capacity of sulfide to split the disulfide bonds of complement factor 3 and immunoglobulin G, deposited on the bacterial surface, was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. There was no detectable effect of 2 mM sulfide on immunoglobulin G. However, sulfide released from opsonized bacteria the beta-chain of C3b C3bi, and the C-terminal part of the alpha-chain of C3bi. This region of the alpha-chain of C3bi has been suggested to bind to the complement receptor 3 of polymorphonuclear leukocytes. The beta-chain of C3b/C3bi may augment the binding of opsonized bacteria to the complement receptors of polymorphonuclear leukocytes. The formation of sulfide by the microflora of the periodontal pockets may provide conditions for the bacteria to escape important parts of the host immune system.

2 siblings, aged 5 years (girl) and 7 years (boy), with periodontitis in the primary dentition were studied. Actinobacillus actinomycetemcomitans was isolated from the gingival pockets of both children. The titers of IgG antibodies against A. actinomycetemcomitans were elevated, and the polymorphonuclear leukocytes had a decreased capacity to ingest IgG-coated latex particles. Other functions of the polymorphonuclear leukocytes were normal. After antibiotic therapy and for the 7-year-old boy, debridement of the gingival pockets A. actinomycetemcomitans was no longer detectable in the gingival pockets, and the phagocytic capacity of the polymorphonuclear leukocytes was normalized. After 2 1/2 years, A. actinomycetemcomitans was found again in the gingival pockets of the boy, and once more his polymorphonuclear leukocytes had a decreased capacity to ingest IgG-coated latex particles. The antibiotic therapy was repeated and 6 months later, the number of A. actinomycetemcomitans was very low and the phagocytic capacity of the polymorphonuclear leukocytes was back to normal. This case report suggests that A. actinomycetemcomitans may be involved in the etiology of periodontitis in the primary dentition, possibly by triggering a phagocytic dysfunction of polymorphonuclear leukocytes.