Pronounced Inflammatory Changes Research Articles

Морфологічні особливості системи мати–плацента–плід на фоні інфекцій, що передаються статевим шляхом

The objective: to identify morphological substrate of placental disorders in women with urogenital infections and miscarriages and spontaneous abortions, as well as women diagnosed with «sexually transmitted infections» who gave birth at term. Materials and methods. A morphological study of samples from 80 women of reproductive age was performed. Patients were divided into 4 groups. At the first stage, histological and immunofluorescent studies of abortuses were performed in two groups of women with spontaneous abortions and missed abortions. The I group consisted of samples from 20 patients with urogenital infections, the II group – samples from 20 uninfected women. At the first stage, a morphological (histological and immunofluorescent) study of abortions was performed in two groups of women with missed and spontaneous abortions. The III group consisted of samples from 20 patients with urogenital infections, the IV group (control) – 20 samples from uninfected women. The second stage involved organometric and histostereometric examination of the placenta from women diagnosed with «sexually transmitted infections» without differentiating the forms of the infectious process (main group, n=10), who gave birth at term, and women who were uninfected (control group, n=10) and also gave birth at term. Results. Morphological study of abortuses from infected patients showed that urogenital infections are characterized by pronounced inflammatory changes in the form of deciduitis (9 specimens – 45%); chorionitis (5 specimens – 25%) and syncytial endometritis (2 specimens – 10%). The morphological picture of necrobiosis was revealed in 25% of samples (5 specimens). In addition, amnionitis (6 specimens – 30%), villisitis (4 specimens – 20%) and basal deciduitis (3 specimens – 15%) were detected. In the group of uninfected women, the leading pathomorphological changes were signs of placental immaturity and changes in vascularization and sclerosis of the villi. Most of the studies of placenta and membranes from women who gave birth at term and had urogenital infection showed significant changes in the villous chorion with the involvement of villi of different calibers. There was a significant increase in the proportion of micropathology. The presence of small necrosis of villi was established in almost 1/3 of all cases, extensive areas of necrosis occurred, but there was no significant difference between two groups. There was a decrease in the volume of the chorionic epithelium compared with the control group. Conclusions. Pathomorphological changes of abortuses and placentas in women with STIs reflected the main links in the pathogenesis of infectious and inflammatory processes and were different from such changes in the absence of this pathology. In particular, urogenital infection is characterized by changes associated with inflammatory manifestations in abortuses, and in the group of uninfected women - with signs of placental immaturity and changes in vascularization and sclerosis of the villi. Histostereometry also revealed significant differences in the structure of the placentas of women of the main and control groups, in particular, a significant increase in the proportion of micropathology. Therefore, the prevention of pregnancy complications and pregravid preparation in women diagnosed with STIs is essential for preventing reproductive failures. Keywords: sexually transmitted infections (STIs), spontaneous abortion, missed abortion, placenta, histostereometry.

Effect of carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in induced fatty liver disease in Wistar rats

Non-alcoholic fatty liver disease (NAFLD) is now a common liver disease affecting about a third of the world's population. In this regard, the issue of studying the pathogenetic factors of the development of this disease in order to select adequate drug therapy and biologically active substances with antioxidant properties regulating the balance of pro- and anti-inflammatory cytokines is of particular relevance. The aim of the study was to assess the effect of minor biologically active substances - carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in the experimental model of the initial stage of NAFLD. Material and methods. The studies were performed on male Wistar rats with initial body weight of 150±10 g. Animals were divided into 5 groups of 8 rats each. Within 8 weeks, rats of the 1st group (control) received a complete modified diet AIN93M, in which soybean oil was replaced with sunflower oil and lard (1:1). Rats of the experimental groups consumed high-calorie choline-deficient diet (HCCDD), in which fat content was 45%, fructose content - 20% of the energy value of the diet. Rats of the 2nd group were fed HCCDD without any supplements, the 3rd group - with the addition of carnosine (75 mg/kg body weight), the 4th group - with the addition of α-lipoic acid (75 mg/kg body weight), the 5th group - with the addition of carnosine and α-lipoic acid in a total dose of 150 mg/kg body weight. The study of rat hepatocyte apoptosis was performed by flow cytometry. Hepatocytes were stained with annexin V and vital dye 7-aminoactinomycin, followed by detection on an flow cytometer. The content of cytokines and chemokines (IL-1α, IL-10, IL-17А, M-CSF, MIP-1α, MIP-3α, RANTES) in the cytoplasmic fraction of liver tissue was determined by multiplex immunoassay. Results and discussion. On the model of the initial stage of development of NAFLD in male Wistar rats the еnrichment of HCCDD with carnosine and α-lipoic acid had demonstrated a protective effect on hepatocytes with a decrease in apoptosis intensity to the level in control rats. Under the influence of HCCDD, an increase in the content of M-CSF and MIP-1α and a decrease in the levels of MIP-3α and RANTES, stimulating the migration and differentiation of various immunoregulatory populations to the parenchyma at an early stage of the formation of fatty hepatosis, in the cytoplasmic fraction of liver tissue were detected. Moreover, a decrease in the level of proinflammatory cytokines IL-17A and IL-1α and an increase in IL-10 produced mainly by Treg-populations indicate the absence of pronounced inflammatory changes in the liver of male Wistar rats at the initial stages of development of fatty dystrophy. Conclusion. Enrichment of HCCDD with both carnosine and α-lipoic acid in Wistar rats had a protective effect on hepatocytes with a decrease in apoptosis to a level in control rats. The increase in the IL-10/IL-17A ratio indicates the activation of anti-inflammatory mechanisms due to the functional predominance of Treg-cells over Th1/Th17 lymphocytes.

THE EFFECT OF PHOTODYNAMIC THERAPY AND PLATELET-ENRICHED PLASMA ON THE HEALING OF SKIN RADIATION ULCERS INFECTED BY STAPHYLOCOCCUS AUREUS.

To determine in experiment the quality of healing of skin radiation ulcers infected with Staphylococcusaureus (S. aureus) under the photodynamic therapy (PDT) administration and the use of platelet-rich plasma (PRP). The experiment was performed on 95 male WAG rats of 6 months of age, which were divided into three groups. Group 1 included animals in whom a skin radiation ulcers in the thigh area was simulated, followed by application of a 0.2 ml suspension of reference strain of S. aureus to its surface on the 7th day after irradiation. Group 2 included animals with S. aureus-infected skin radiation ulcers, in whom the PET was administered aday after infection contamination. Group 3 included animals with S. aureus-infected skin radiation ulcers, in whomthe PDT was administered a day after infection in the morning, and the PRP was manifold injected in periwound areain the afternoon. The skin with underlying soft tissues from the area of radiation damage were the material for morphological examination. The hematoxylin and eosin, picrofuxin according to van Gizon, Mallory staining wereapplied to micropreparations. A morphometric study was conducted. In animals with skin radiation ulcers, in whom the PDT was administered upon infection with S. aureus(group 2), compared with animals with simulated infected skin radiation ulcers without treatment (group 1), Theactivation (i.e. accelerating) of the healing occurred for the period from the 14th to the 52nd day of experiment dueto the active processes of wound cleansing from necrotized tissues, less pronounced inflammatory changes in thelesion, and active of appearance and maturation of granulation tissue, less pronounced hemodynamic, ischemic andalternative disorders in the dermis, hypodermis, muscle tissue surrounding the wound cavity, activation of proliferative processes in epithelial layer localized in the marginal parts of the wound. Formation of pathological (hypertrophic or keloid) scar of the skin was the result of healing of skin radiation ulcer infected with S. aureus. In animalswith radiation ulcers infected with S. aureus, in the case of PDT and PRP (group 3) the regenerative process wasdirected not only at accelerating the rate of healing, but also on restoration of original structure of the lost parts ofthe skin compared with only PDT administration (group 2). Acceleration of the healing of the infected skin radiation ulcer in animals of groups 2 and 3 was due to similar processes. Photodynamic therapy activates and accelerates the healing process of skin radiation ulcers infectedwith S. aureus and leads to formation of a pathological scar (hypertrophic or keloid). Healing of the infected S. aureusradiation ulcers occurs more actively upon the photodynamic therapy administration in combination with multipleperiwound injections of the platelet-enriched plasma, compared with only photodynamic therapy administration,and finishes with an organotypic regeneration and almost complete skin recovery.

A Technique for Wound Cavity Closure after Coccyx Resection in Experiment

Introduction. Closing the wound cavity after the coccyx resection in patients with posttraumatic coccygodynia remains an issue unresolved. Closing the wound cavity with local tissues often leads to the wound dehiscence due to excessive tension which in turn leads to suppuration and prolonged healing.This paper aims to assess experimentally the effectiveness of using ground autograft bone of the coccyx removed for the closure of the surgical wound.Materials and methods. In the animal experiment the coccyx resection was performed under a combined anaesthesia in six pigs (three in the study group and three in control). In the control group the wound edges were sutured to its floor. In the study group after the coccyx resection the ground bone mass made of the coccyx resected was implanted into the wound cavity.Results and discussion. In the control group the wound dehiscence was registered in all the animals. After the animals were taken out of the experiment it was established that in the study group a new consolidated bony conglomerate was formed without any pronounced inflammatory changes around the wound. In control the wound cavity healed with secondary intention.Conclusions. The study confirms the effectiveness of using ground autograft bone for the closure of the wound cavity.

Rheumatoid nodules in the lung parenchyma in rheumatoid arthritis

Rheumatoid nodules (RNs) are one of the most common extra-articular manifestations of rheumatoid arthritis (RA), but are rarely located in lung tissue. The development of extra-articular (systemic) manifestations of RA is associated with the high levels of rheumatoid factor and anticyclic citrullinated peptide antibodies. The specific features of the course of RNs in lung tissue are their frequent occurrence with minimally pronounced joint inflammatory changes or remission. In rare cases, RNs are prone to disintegration and suppuration, which may be complicated by the formation of small caverns, hemoptysis, and, if located subpleurally, pneumothorax. In addition, there are publications on the possible relationship of the formation of RNs and their accelerated development to the administration of immunosuppressive drugs (methotrexate, tocilizumab, D-penicillamine, gold salts, leflunomide, infliximab, and other TNF-α inhibitors) and on the association of pulmonary RNs with methotrexate treatment. The paper describes a clinical case of a female patient with RA-systemic sclerosis overlap syndrome and RN formation in lung tissue early at disease onset when the DAS28 target level for RA has been achieved. The atypical outline of a pulmonary nodule has required a differential diagnostic search. The results of imaging RNs in the lung and their dynamics are shown. The given data are discussed.

The Effect of Co-infection of Food-Borne Pathogenic Bacteria on the Progression of Campylobacter jejuni Infection in Mice.

Campylobacter is a well-known food-borne pathogen that causes human gastroenteritis. Food products that contain Campylobacter may also be contaminated by other pathogens, however, whether this multiple contamination leads to more severe infection remains unclear. In this study, mice were gavaged with Campylobacter jejuni and other food-borne pathogenic bacteria to mimic a multiple infection. It was demonstrated that the C. jejuni load was elevated when the mice were co-infected with C. jejuni and Salmonella typhimurium, and the campylobacteriosis that followed was also enhanced, with features of decreased body weight, heavier bloody stools and more pronounced inflammatory changes to the colon. In addition, infection with C. jejuni was also promoted by co-infection with entero-invasive Escherichia coli but unaffected over time. In contrast to S. typhimurium and entero-invasive E. coli, co-infection by Listeria monocytogenes showed little effect on C. jejuni infection and even hindered its progress. In addition, the intestinal microecology was also affected by co-infection of C. jejuni with other pathogens, with an increased relative abundance of unclassified Enterobacteriaceae, decreased levels of butyric acid and changes in the abundance of several genera of gut microbe, which suggests that some food-borne pathogenic bacteria might affect the progression of C. jejuni infection in mice by influencing the composition of the gut microbiota and the resulting changes in SCFA levels. Collectively, our findings suggest that co-infection of Campylobacter with other pathogenic bacteria can impact on the progression of infection by C. jejuni in mice, which may also have implication for the etiology of Campylobacter on human health.

Anti-epileptogenic and Anti-convulsive Effects of Fingolimod in Experimental Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) represents a devastating neurological condition, in which approximately 4/5 of patients remain refractory for anti-convulsive drugs. Epilepsy surgery biopsies often reveal the damage pattern of "hippocampal sclerosis" (HS) characterized not only by neuronal loss but also pronounced astrogliosis and inflammatory changes. Since TLE shares distinct pathogenetic aspects with multiple sclerosis (MS), we have here scrutinized therapeutic effects in experimental TLE of the immunmodulator fingolimod, which is established in MS therapy. Fingolimod targets sphingosine-phosphate receptors (S1PRs). mRNAs of fingolimod target S1PRs were augmented in two experimental post status epilepticus (SE) TLE mouse models (suprahippocampal kainate/pilocarpine). SE frequently induces chronic recurrent seizures after an extended latency referred to as epileptogenesis. Transient fingolimod treatment of mice during epileptogenesis after suprahippocampal kainate-induced SE revealed substantial reduction of chronic seizure activity despite lacking acute attenuation of SE itself. Intriguingly, fingolimod exerted robust anti-convulsive activity in kainate-induced SE mice treated in the chronic TLE stage and had neuroprotective and anti-gliotic effects and reduced cytotoxic T cell infiltrates. Finally, the expression profile of fingolimod target-S1PRs in human hippocampal biopsy tissue of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure relief suggests repurposing of fingolimod as novel therapeutic perspective in focal epilepsies.

МОРФОЛОГИЧЕСКОЕ СОСТОЯНИЕ ПЕЧЕНИ У НОВОРОЖДЕННЫХ С ВРОЖДЕННОЙ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИЕЙ

The aim of the study was to study the morphological structure of the liver in newborns with congenital cytomegalovirus infection. The material for the study was the liver of 36 full-term newborns who died on the 2nd-5th day of life from birth trauma, intranatal and postnatal hypoxia. The main study group included 16 full-term newborns with congenital cytomegalovirus infection. The comparison group included 20 newborns from mothers without any viral infections, as well as moderate, severe somatic diseases and obstetric pathology during pregnancy, and these babies died at the 2nd-5th day of life from birth trauma, intrapartum and postnatal hypoxia. The main cause of death of children of early neonatal age was intrauterine infection which was clinically manifested by moderate or severe cerebral ischemia with hypertension-hydrocephalic syndrome, pseudocysts of the vascular plexus, subependymal and subarachnoid hemorrhages, monocytosis, vesiculosis, pneumonia, hepatitis and meningoencephalitis and antenatal hypoxia caused by the development of subcompensated placental insufficiency. When describing the liver, the attention was drawn to the following macroscopic and pathohistological changes in the organ: 1) the condition of the capsule of the organ; 2) the change of the general plan of a structure; 3) the reaction of the bloodstream of the liver: 4) the condition of the portal tracts; 5) the state of the lumen of the bile ducts and its epithelium. The material was fixed in 10% neutral formalin, dehydrated in alcohols and poured into paraffin. For observational microscopy, histological sections 5-7 μm thick were stained with Böhmer hematoxylin and eosin. Morphological examination of the liver in the newborns of the main group showed an increase in the frequency of detection of subcapsular hematomas, pronounced congestion of sinusoids, foci of lymphohistiocytic infiltration of the connective tissue of the portal tracts, small-focal proliferation of Kupffer cells, alterative and proliferative changes in the epithelium of the bile ducts, as well as cells with viral metamorphosis. The revealed structural changes in the morphological structure of the liver in full-term newborns indicate the development of pronounced dyscirculatory, alterative and inflammatory changes in the liver of cytomegalovirus genesis.

Лапароскопическая холецистэктомия при остром калькулезном холецистите у больных, ранее оперированных на органах брюшной полости

Реферат
 Цель. Изучение эффективности дооперационной диагностики и лапароскопических методов коррекции спаечной болезни (СБ) у больных с острым калькулезным холециститом (ОКХ).
 Материалы и методы. Проведен анализ эффективности дооперационной диагностики и лапароскопических методов коррекции СБ у 110 пациентов с ОКХ, ранее перенесших оперативные вмешательства на органах брюшной полости.
 Результаты. Диагностическая ценность сонографии при СБ высокая. Использование ультразвукового скальпеля (УЗС) у больных с выраженными местными воспалительными изменениями тканей в области желчного пузыря и сопутствующей СБ имеет преимущества.
 Выводы. Применение УЗС - наиболее эффективный и безопасный метод рассечения спаек и разъединения инфильтрата при ОКХ.

EVALUATION OF UVEITIS ACTIVITY USING BOS24 IN PATIENTS WITH BEHСET'S DISEASE

Objective:to estimate changes of uveitis activity using BOS24 (Behсet's disease Ocular attack Score 24) during antiinflammatory and immunosuppressive therapy in patients with Behcet's disease (BD).Subjects and methods.103 (75.6%) of the 138 patients with BD fulfilled the 1990 International Study Group for Behсet's Disease (ISGBD) criteria had eye lesions; 55 (53.4%) of the 103 patients had an exacerbation of uveitis. 55 patients with an exacerbation of uveitis were found to have active inflammation in 94 eyes. The activity of uveitis was monitored during anti-inflammatory and immunosuppressive therapy, by using BOS24 that consists of 6 parameters with maximal possible value 24.Results and discussion.The mean BOS24 for 94 eyes with active uveitis at baseline was 9.33±0.91. The most pronounced inflammatory changes were found in the posterior chamber of the eye, mainly in the area of the peripheral retina, rarely in the area of the fovea and in the optic disc. All the patients with an exacerbation of uveitis received systemic therapy with glucocorticoids, cyclosporine and/or azathioprine. After 8.92±3.47 months of treatment, the mean BOS2 decreased significantly (p < 0.001) to 2.20±1.02. The most substantial positive changes were noted in the anterior chamber of the eye (p = 0.03), vitreous humor (p < 0.01), and peripheral retina (p < 0.001).Conclusion. BOS24 is a reliable tool to quantify uveitis activity in patients with BD and its dynamics during antiinflammatory and immunosuppressive therapy.

Insulin Resistance in Patients with Chronic Hepatitis C

Abstract Introduction. Insulin resistance is the most common extrahepatic manifestation associated with hepatitis C virus, which leads to developing more pronounced fibrosis and liver steatosis. The aim of the study was to assess the prevalence of insulin resistance in non-diabetic, treatment naive patients with chronic hepatitis C and to analyze the relation of insulin resistance with genotype, viral load, gender, age, laboratory parameters, inflammatory and fibrotic changes in the liver, body mass index (BMI) and the presence of steatosis. Methods. In this cross sectional study, 224 patients with hepatitis C viral infection were included. The patients were divided into two groups. The first group was with no insulin resistance and the second one with present insulin resistance. They were compared in terms of genotype, viral load, gender, age, inflammatory and fibrotic changes in the liver, BMI and liver steatosis. Results. Insulin resistance was present in 45.5% of patients. The following factors were associated with insulin resistance: age (p=0.0022), inflammatory and fibrotic changes in the liver (p=0.001, p=0.006, respectively), steatosis (p=0.015) and transaminase activities (for AST, p=0,002, for ALT, p=0.001). Conclusion. In the Republic of Macedonia, a high percent of 45.5% among non-diabetic and treatment naïve patients with chronic viral hepatitis C, had insulin resistance. Insulin resistance was more prevalent in older patients, in those with more pronounced inflammatory and fibrotic changes in the liver, in patients with steatosis and in those with higher transaminase activity.

Structural and Functional Basis of Chronic Pelvic Pain Syndrome during Combined Chronic Cystitis and Adenomyosis.

Comprehensive clinical and morphological examination of 60 female patients with chronic pelvic pain syndrome after combined chronic cystitis and adenomyosis was carried out. In all patients, the complex urodynamic examination revealed various disturbances of urination and stasis-like abnormalities of circulation in vesical and uterine walls. The pathomorphological peculiarities of the urogenital disorders during combination of adenomyosis and cystitis (of the combined proliferative and erosive/destructive type) is manifested by more pronounced destructive and inflammatory changes in urothelium characterized by the formation of superficial and deep erosions as well as by association of erosive/destructive damages to the urothelium with proliferative and metaplastic changes. Combined treatment of chronic cystitides and adenomyosis eliminated the destructive and inflammatory alterations in the vesical mucosa in 70 and 93% female patients, respectively (the corresponding values after basic therapy were 60 and 77%), and pronouncedly ameliorated pain syndrome.

Clinical Study of the Influence of Implants Made of Different Metals on the Physical Status of Experimental Animals

Biocompatibility of implants made of steel 12X18H9T, steel 12X18H9T coated with titanium and hafnium nitrides, and steel 12X18H9T coated with titanium and zirconium nitrides was studied in rats. Implants that represented pins 8-10 mm long and 0.5 mm in diameter were inserted intramedullary into the middle third of the tibia after drilling. The ends of pins were turned down and placed under the skin. The wound was sutured tightly. Dynamics of body weight and temperature as well as the condition of the hair, eyes, oral and nasal mucosa were assessed on days 10, 30, 60 and 90 after implantation. It was shown that implants coated with titanium and hafnium nitrides caused minimum systemic and local reactions while implantation of pins coated with titanium and zirconium nitrides resulted in the development of more pronounced inflammatory changes on both the local and systemic level.

Clinical Study of the Influence of Implants Made of Different Metals on the Physical Status of Experimental Animals

Biocompatibility of implants made of steel 12X18H9T, steel 12X18H9T coated with titanium and hafnium nitrides, and steel 12X18H9T coated with titanium and zirconium nitrides was studied in rats. Implants that represented pins 8-10 mm long and 0.5 mm in diameter were inserted intramedullary into the middle third of the tibia after drilling. The ends of pins were turned down and placed under the skin. The wound was sutured tightly. Dynamics of body weight and temperature as well as the condition of the hair, eyes, oral and nasal mucosa were assessed on days 10, 30, 60 and 90 after implantation. It was shown that implants coated with titanium and hafnium nitrides caused minimum systemic and local reactions while implantation of pins coated with titanium and zirconium nitrides resulted in the development of more pronounced inflammatory changes on both the local and systemic level.

Clinical, radiological and pathomorphological changes in the tissues of the shoulder and elbow joints in patients with rheumatoid arthritis

Clinical and morphological picture of rheumatoid arthritis (RA) is characterized by a complex combination of inflammatory, distrophic, destructive, reparative, and sclerosing processes in the tissues of the joints. However structural changes in the tissues of the upper limb joints (shoulder and elbow) in cases of RA understudied. Objective: to set clinical, radiological and pathomorphological features of the tissue in the shoulder and elbow joints in patients with RA. Methods: we investigated the tissues of the shoulder or elbow joints in six patients with RA who underwent total joints replacement with the removal of fragments of the articular ends of bones and the joint capsule using clinical, radiologic and pathomorphologic analysis. Sections were stained with hematoxylin and eosin. It was found that complex pathological changes in the tissues of the articular ends and of the joint capsule are based on the functional insufficiency of the shoulder and elbow joints. Although chronic inflammatory process with an immune component of varying intensity, more often of mild or moderate intensity, is the leading factor of damage to normal structures of the joints in late terms of the disease dystrophic and destructive changes in the articular ends of bones acquire the greatest value. More pronounced dystrophic, destructive and chronic inflammatory changes noted in the shoulder joint have corresponded to morphological picture of osteoarthritis of moderate or severe grade reflecting as individual metabolic processes, topography and activity of rheumatoid inflammation as biomechanical features of the joints.

Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis

In a rabbit model, we have previously reported evidence for a pathogenic role of streptococcal IgG Fc-binding proteins (IgGFcBP) in poststreptococcal glomerulonephritis (PSGN). These proteins, of the M protein family, were shown to trigger anti-IgG production and enhance renal deposition of IgG and/or immune complexes (ICs), with resulting activation of complement and cytokine cascades. In the present study, type M12/emm12, group A streptococci (GAS) were found often to bind artificial ICs, viz. peroxidase-anti-peroxidase rabbit IgG (PAP) or tetanus toxoid-anti-tetanus human IgG (TAT), rather than monomeric IgG. Animals injected with each of four IC binding clinical isolates (from patients with scarlet fever or PSGN) showed pronounced inflammatory and degenerative glomerular changes, morphologically similar to human PSGN, with membrane thickening and IgG and complement C3 deposition, as well as secretion of IL-6 and TNF-α by mesangial and endothelial cells. In contrast, non-binding strains (two from asymptomatic carriers and one from a PSGN case) failed to trigger any renal changes. Only the IC binding strains induced elevated titres of anti-IgG. Though the streptococcal binding component(s) has not been demonstrated, the selective binding of ICs by type M12/emm12 strains appears important for the well-known, marked nephritogenic potential of this GAS type.

Transcapsular Arterial Neovascularization after Liver Transplantation in Pediatric Patients Indicates Transplant Failure

To identify transcapsular arterial neovascularization with Doppler ultrasonography (US) in pediatric patients after liver transplantation and to assess the frequency of the finding, its underlying causes, and its relevance in terms of clinical outcome. The study was approved by the local ethics committee, with waived informed consent. All pediatric patients who underwent liver transplantation between January 2000 and December 2003 were retrospectively evaluated. Patients were followed up until June 2008, by using a predefined US protocol with prospective documentation. Of 182 consecutive liver transplantations performed in 162 patients (mean age, 4.5 years; range, 0.1-18.4 years) in this period, 25 patients with a total of 27 liver transplantations underwent US examinations conducted by multiple investigators and were primarily excluded. Student t tests and χ(2) tests were performed where appropriate. The Tarone-Ware test was used to compare transplant survival times. Transcapsular arterial neovascularization was noticed in 13 of 137 patients (9.5%) and in 13 of 155 liver transplants (8.4%). The mean time until arterial neovessels appeared was 157 days after liver transplantation (median, 97 days; range, 19-477 days). Arterial neovascularization was associated with pronounced transplant malperfusion and inflammatory changes (P < .001). Patients with transcapsular arterial neovascularization had a significantly shorter mean transplant survival time (1426.4 days ± 244.5 [standard error], with 95% confidence interval: 947.23, 1905.23, vs 2526.4 days ± 92.1, with 95% confidence interval: 2345.84, 2706.97; P = .008) and a higher retransplantation rate (53.8% vs 19.7%, P = .009). Transcapsular arterial neovascularization, detected with color Doppler US, occurred in 9.5% (13 of 137) of pediatric patients and 8.4% (13 of 155) of liver transplants and was associated with underlying malperfusion and inflammation. The diagnosis of transcapsular arterial neovascularization was associated with reduced graft survival times and a high retransplantation rate. The negative prognostic value of the sign may assist in a strategy of organ allocation.

Serum anti-inflammatory markers in general population subjects with elevated depressive symptoms

Anti-inflammatory substances have previously been suggested to show compensatory elevations in depressed individuals with pronounced inflammatory changes. In order to further clarify these observations, we examined depression-related alterations in the serum levels of anti-inflammatory markers interleukin (IL)-1 receptor antagonist (RA) and IL-10 and the pro-inflammatory marker IL-6 in 416 general population participants. Depression was evaluated with the Beck Depression Inventory (BDI). Participants with elevated depressive symptoms (BDI > 14, n = 44) had increased levels of IL-1 RA and IL-6. No changes were observed in their IL-10 levels. In multivariate modeling with adjustments for age, gender, obesity, regular smoking, alcohol use, metabolic syndrome, physical exercise, sleep disturbance, and the use of non-steroidal anti-inflammatory drugs, a high level of IL-1 RA was associated with an increased likelihood of belonging to the group with elevated depressive symptoms (OR for each 1 SD increase in the serum level of IL-1 RA: 2.17, 95% CI 1.35–3.48, p = 0.001). The significance of IL-6 alterations did not persist in the same model. The pronounced secretion of anti-inflammatory marker IL-1 RA may reflect the presence of compensatory mechanisms during a depression-related inflammatory state.

Effects of a recombinant surfactant protein-C-based surfactant on lung function and the pulmonary surfactant system in a model of meconium aspiration syndrome*

Meconium aspiration syndrome (MAS) remains a relevant cause of neonatal respiratory failure and is characterized by severe impairment of pulmonary gas exchange, surfactant inactivation, and pronounced inflammatory changes. Surfactant administration has been shown as an effective treatment strategy in MAS. The present study aimed at investigating the impact of a recombinant surfactant protein (SP)-C-based surfactant on pulmonary gas exchange and lung function in this model of neonatal lung injury. Furthermore, SP-B and -C were determined on the transcriptional and protein level. Laboratory experiment. University laboratory. Twenty three newborn piglets (median age 6 days, weight 1900-2500 g). Piglets were intubated and mechanically ventilated and then received 20% sterile meconium (5 mL/kg) for induction of lung injury. After 30 mins, animals were randomized for control (n = 7, MAS controls), recombinant SP-C surfactant (n = 8), or natural surfactant (n = 8). Surfactant preparations were administered as an intratracheal bolus (75 mg/kg), and animals were ventilated for another 330 mins. Nonventilated newborn piglets at term (n = 28; median weight 1484 g, range 720-1990 g) served as a healthy reference group (healthy controls). Lung function variables, arterial blood gas samples, and lung tissues were obtained. Expression of SP-B and -C messenger RNA was quantified in left lung lobe tissue using real-time polymerase chain reaction. Protein concentrations were determined by enzyme-linked immunosorbent assay. Scanning electron microscopy and transmission electron microscopy were performed in tissue samples of the right lung lobe. Compared with healthy controls, SP-B messenger RNA expression was significantly increased in MAS (p < .02), whereas SP-C messenger RNA expression was found to be significantly reduced (p < .001). SP concentrations, however, were not significantly different. Although a significant improvement of gas exchange and lung function was observed after surfactant administration in both groups, surfactant messenger RNA expression and protein concentrations were not significantly altered. Scanning and transmission electron microscopy showed severe pulmonary ultrastructural changes after meconium aspiration improving after surfactant treatment. Impairment of lung function in MAS, associated with marked changes in SP messenger RNA expression, can be sufficiently treated using recombinant SP-C-based or natural surfactant. Despite improved lung function and gas exchange as well as pulmonary ultrastructure after treatment, pulmonary SP messenger RNA expression and concentrations remained significantly affected, giving important insight into the time course following surfactant treatment in MAS.

Role of group A streptococcal IgG-binding proteins in triggering experimental glomerulonephritis in the rabbit.

Our previous studies have indicated that the IgG-binding M-family proteins (IgGBP) of group A streptococci may be involved in eliciting experimental acute poststreptococcal glomerulonephritis (APSGN) in the rabbit. These surface proteins were also found to trigger production of anti-IgG, which might conceivably act to enhance renal deposition of immune complexes (IC). In the present study, a clinical isolate of serotype M22 (strain AL168), an isogenic double mutant deficient for both the IgGBPs Mrp and Emm, as well as mutants deficient in only one of the proteins were tested for capacity to induce glomerulonephritis. Streptococci to be used for injecting rabbits were heat-killed. Surface-bound IgG was removed by 1 M KSCN and cells were then repeatedly washed in PBS before use. Rabbits were injected intravenously with 109 cells three times a week for 8 weeks and, following one month of rest, for another 6 weeks. Deposits of IgG and C3 as well as induced chemokines TNF-alpha, IL-1beta and IL-6 were traced in cryostat sections using specific antibodies and appropriate peroxidase-labelled anti-antibodies. In four rabbits immunized with the double mutant strain, no deposits were found, and as examined by TEM, only subtle and transient renal changes were observed. In contrast, the original strain AL168 induced pronounced inflammatory and degenerative glomerular changes in all four rabbits injected, and deposits of TNF-alpha, IL-1beta and IL-6 were found in mesangial and endothelial cells. Similar deposits and glomerular changes were seen in all eight rabbits injected with the mrp-emm+ mutant and in four out of seven animals receiving the mrp+emm- mutant. There was a highly significant correlation between high levels of circulating anti-IgG and development of APSGN. These results confirm an important role of streptococcal IgGBP in triggering experimental APSGN as earlier proposed by our group.