Regulatory T Cells in the Context of New-Onset Diabetes After Renal Transplant: A Single-Center Experience.

BACKGROUND: New-onset diabetes mellitus after transplant (NODAT) is a well-known complication of renal transplant that severely affects graft and patient survival. It is necessary to explore further risk factors and reveal the underlying pathomechanism. METHODS: Renal transplants performed between January 2010 and June 2018 were involved. Exclusion criteria were the recipient age younger than 18 years, follow-up period less than 6 months, and patients with diabetes at the time of transplant. Only primary kidney transplants were involved in our study, which totaled 223 cases. Besides donor and recipient demographic data, the type of immunosuppression, the average fasting glucose level, and T-subset profiles were compared. RESULTS: Of 223 cases there were 33 patients (14.8%) with NODAT (17 female; mean age, 54.2 [SD, 10.3] years; mean body mass index [calculated as weight in kilograms divided by height in meters squared], 27.8 [SD, 5.1]; mean follow-up, 43.3 [SD, 25.5] months). The control group consisted of 190 patients. The average fasting blood glucose level was higher in the NODAT group vs the control group (P < .001). The average fasting blood glucose level above diabetic threshold (≥7 mmol/L) was in association with a 6-fold higher risk of NODAT (odds ratio, 5.86; 95% CI, 2.46-13.97; P < .001). Absolute value of CD4+CD25brightCD127dim regulatory T cells was lower in the NODAT group at the first month after transplant (P = .048) Immunosuppressive protocol and survival data did not differ. CONCLUSIONS: Intensive management of the carbohydrate excursions during the early post-transplant period may decrease the incidence of NODAT. Further investigations will be required to decide whether the reduced CD4+CD25brightCD127dim/regulatory T-cell count contributes the development of NODAT.

Promotion of the crosslinking of fibrin and alpha 2-antiplasmin by platelets.

Factor XIII (FXIII) is of high importance in the regulation of fibrinolysis. It crosslinks alpha 2-antiplasmin (alpha 2AP) and fibrin and by this way protects fibrin from the prompt elimination by plasmin. Although FXIII of platelets has been implicated in this protective mechanism, the role of platelets and platelet FXIII in the crosslinking process is far from being elucidated. As demonstrated by SDS PAGE and by immunoblotting for alpha 2AP, intact normal platelets resuspended in FXIII-free plasma or FXIII-free fibrinogen solution catalyzed the crosslinking of fibrin chains and also the crosslinking of alpha 2AP to fibrin alpha-chains. With FXIII-deficient platelets no crosslinking reaction could be observed indicating that the crosslinking with normal platelets was, indeed, due to platelet FXIII and not to another, putative platelet transglutaminase. However, the crosslinking of alpha 2AP to fibrin induced by the FXIII of intact platelets resuspended in FXIII-free plasma was considerably less extensive than the crosslinking carried out by the FXIII of normal plasma in the presence of FXIII-free platelets. Furthermore, the replacement of FXIII-free platelets by normal platelets in normal FXIII-containing plasma resulted in little, if any, difference in the crosslinking process. When crosslinking was induced by highly purified plasma FXIII the presence of intact FXIII-free platelets significantly accelerated the formation of alpha-chain polymers as well as the incorporation of alpha 2AP-fibrin alpha-chain hetero-dimer into these polymers. The results indicate that, in physiological conditions, platelet FXIII plays only a minor role in the crosslinking of alpha 2AP and fibrin; however, platelets, independently of their FXIII content, promote the crosslinking reaction by providing a catalytic surface on which the formation of highly crosslinked fibrin polymers is accelerated.

Pathogenicity and virulence of coagulase negative staphylococci in relation to adherence, hydrophobicity, and toxin production in vitro.

AIMS: To study the pathogenicity and virulence characteristics of Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus sapro-phyticus. METHODS: BALB/c mice were challenged intraperitoneally with graded doses of three strains belonging to each species. LD50s were measured for each strain. Haemolysin (alpha- and delta-) and enzyme (DNAase, lipase, and esterase) production in vitro were measured qualitatively and quantitatively. Adhesion to plastic was measured and related to cell surface hydrophobicity among the strains. RESULTS: S saprophyticus proved the most virulent (LD50 = 2.7-2.9 x 10(7) cfu/g body weight) while S epidermidis was the least virulent (LD50 = 6-8 x 10(7) cfu/g body weight). An enlarged spleen was the most common macroscopic pathological feature. Kidney, liver, and more rarely peritoneal abscesses were also seen in the infected animals. No direct correlation was found between adherence in vitro, cell surface hydrophobicity, or toxin/enzyme biosynthesis and virulence in mice. CONCLUSION: The results show that coagulase negative staphylococci are pathogenic in BALB/c mice. It is clear that these bacteria can cause invasive disease. However, the in vitro characteristics of coagulase negative staphylococci are not related to the pathogenicity of the organisms in mice.

Motoneurons differ in size and peripheral target in the trigeminal and facial nuclear complex of the frog.

The cobalt labelling technique was applied to different branches of the frog trigeminal and facial nerves and the representation of muscle supplied by these nerves were studied. (1) The levator bulbi muscle is innervated by a small group of neurons localised in its rostromedial part of the trigeminal motor nucleus (nV). (2) The jaw closer muscles are represented in the rostral two thirds of the nV. (3) Muscles of the floor of the mouth, which contribute to the jaw opening, and the depressor mandibulae muscle are innervated from the caudal one third of the nV and from the facial motor nucleus, respectively. There were distinct differences in the shape and size of perikarya innervating these three functionally different muscle groups.

[Pathogenic properties of coagulase-negative staphylococci in experimental infections]. / Koaguláz-negatív staphylococcusok patogenetikai tulajdonságai experimentalis fertözésekben.

The frequency of persistence of three Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus saprophyticus strains, respectively, was studied in BALB/c mice at the 10th day of intraperitoneal (ip) challenge. 245 out of 416 mice survived after infections with four bacterial suspensions of different colony forming units (CFU) of each strain. Staphylococci persisted in 61 mice (24,9%). The main sites of persistence were the kidneys, while cocci were rarely isolated from the spleen and the liver. S. epidermidis persisted with a significantly higher rate than the other two species, because S. epidermidis in 28,8%, S. haemolyticus in 4,9%, and S. saprophyticus in 3,6% were reisolated from the organs of the respective infected and surviving animals. The organ persistence was proportional to the amount of bacteria injected. The persistence resulted in subacute microabscesses in the organs. Reisolates of persisting bacteria remained stable in phenotype and genotype concerning antibiotic resistance patterns and biochemical activities for the taxonomic implication, whereas cell surface properties characterizable with phage types altered considerably during persistence. It is concluded that cocci of all three Staphylococcus species are invasive and can persist to a certain extent in the organs of animals with normal immune system, too, after artificial inoculation into the peritoneum i. e. to the serosal surfaces.

[Study of the virulence of coagulase-negative staphylococci in experimental infections]. / Koaguláz-negatív staphylococcusok virulenciájának tanulmányozása kísérletes fertözésekben.

The pathogenicity and virulence of 3 strains of Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus saprophyticus, respectively were studied in BALB/c mice by intraperitoneal (ip) challenge using 4 bacterial suspensions of different colony forming units (CFU) of each strain. Strains were isolated from wound, blood, and urine of inpatients. On the base of the lethality rates, S. saprophyticus proved to be the most virulent (LD50 = 2.7-2.9 x 10(7) CFU/g body wt), while the S. epidermidis species was the least virulent (LD50 = 6-8 x 10(7) CFU/g body wt). The lethality rate of male mice was higher than that of the female ones at the same challenge bacterium concentration. Mice of higher body weight were generally more sensitive to a quality of bacteria calculated to 1 g of mice than the lighter mice. The 245 mice surviving the challenge were dissected at the 10th day of infection. Splenomegaly was found to be the most frequent macroscopic pathological alteration. There appeared kidney abscesses, liver abscesses, and rarely peritoneal abscess. The frequency of pathological findings were directly proportional to the amount of bacteria injected. The results indicate that clinical strains of coagulase-negative staphylococci (CNS) examined were pathogenic and virulent for BALB/c mice they are invasive after ip injection and can cause macroscopic pathological changes in parenchymal organs. Thus, ip CNS challenge in mice may be a model to imitate and study infections caused by CNS in human.