Evaluation of vacuum infiltration vitrification and cryo-mesh cryopreservation techniques with Arabidopsis thaliana shoot tips.

BACKGROUND: Novel cryo-techniques are continuously being developed that may better improve cryogenic survival in plants, with the aim of reducing exposure times to otherwise toxic cryoprotective agents whilst maximising regeneration rates. OBJECTIVE: This study used cryo-mesh and vacuum infiltration vitrification with two vitrification solutions (PVS2 and PVS3) to develop an optimised cryopreservation protocol for Arabidopsis thaliana. MATERIALS AND METHODS: Shoot tips from 10-day old seedlings of wild type A. thaliana were cryopreserved using either vacuum infiltration vitrification or the cryo-mesh technique. Shoot tips were treated for up to 60 min in increments of 10 min with PVS2 and PVS3, and for an additional 180 and 300 min incubation for cryo-mesh prior to exposure to liquid nitrogen. RESULTS: Both methods resulted in very high regeneration rates, but which decreased after longer exposure to the vitrification solutions. The highest regeneration rate for vacuum-infiltration vitrification was attained after only 30 min incubation in PVS2 (92.5%) and 50 min incubation in PVS3 (93.6%). In the case of cryo-mesh the highest regeneration was observed after 180 min incubation in either PVS2 (100%) or PVS3 (92.2%). CONCLUSION: Vacuum-infiltration vitrification is more effective than cryo-mesh by reducing exposure times to cryoprotective solutions whilst achieving very high regeneration rates of shoot tips of A. thaliana. https://doi.org/10.54680/fr22610110712.

Platelet transfusion practice and related transfusion reactions in a large teaching hospital.

BACKGROUND: Platelet transfusion practice varies widely since many aspects of platelet concentrate (PC) use have not been definitively determined. The objectives of this retrospective study were to present platelet transfusion practice and evaluate PC and patient characteristics, as well as their association with transfusion reaction (TR) rate. MATERIAL AND METHODS: Platelet transfusions over a 5-year period were analysed regarding PC characteristics (the ABO and RhD compatibility, product type, and storage duration), patient characteristics (most responsible diagnosis, age, and gender), and TR type. RESULTS: A total of 46,351 PCs were transfused: 76.4% whole blood-derived (WBD) and 23.6% single donor apheresis (SDA). Three thousand seven hundred seventy-six patients received platelet transfusions: 24.7% paediatric and 75.3% adult patients, 79.6% outpatients and 20.4% inpatients. As much as 63.1% of all transfused PCs were fresh (stored for≤3 days), 98.0% ABO-identical, and 87.3% of all PCs given to RhD- patients were RhD-. PCs were mainly transfused to haemato-oncology (76.8%) and cardiovascular surgery patients (6.5%). Overall, 84 (0.18%) TRs were reported, with allergic TRs (ATRs) being the most common. Although PC ABO compatibility and storage duration, as well as patient age and gender, showed differences in TR rate, only the use of PCs in platelet additive solution (PAS) showed a statistically significant reduction of TRs (P<0.001). CONCLUSION: Transfusion practice at the University Hospital Centre Zagreb resulted in almost all patients receiving ABO and RhD identical PCs, and most of them were fresh PCs. The most important factor affecting the incidence of TRs was platelet storage solution. The use of PAS effectively reduced the rate of TRs, particularly allergic TRs.

Inflammatory bowel disease and depressive symptoms: the prevalence and factors associated with depression in patients with inflammatory bowel disease on intravenous biological therapy - single center experience.

OBJECTIVE: Depression is one of the most commonly occurring psychiatric comorbidities in patients suffering from inflammatory bowel disease (IBD). This study aims to determine prevalence and risk factors for the more severe symptoms of depression (DP) in IBD patients on intravenous biological therapy (IBT). PATIENTS AND METHODS: The study consisted of 90 IBD patients who completed a Patient Health Questionnaire-9 (PHQ9) to detect symptoms of depression. Demographic information and disease characteristics were collected as well as medication information for these patients. Univariate and multivariate ordinal logistic regression was done to identify risk factors for the DP. RESULTS: Anti-TNF therapy comprised 58.9% of patients and anti-integrin 41.1%. The prevalence of DP (PHQ9score ≥10) among these patients is 20%. For the univariate logistic regression DP was statistically significantly associated with disease activity (OR 6.656; 95% Cl 2.576-17.19, p<0.001), use of corticosteroids (OR 4.224; 95% Cl 1.658-10.76, p = 0.003) and thiopurine (OR 2.502 95% Cl 1.031-6.069, p = 0.042), as well as relationship status (single, in relationship or married) (OR 0.391; 95% Cl 0.173-0.885, p = 0.024). The multivariate analysis indicated that the risk of developing DP was associated with disease activity (OR 5.708; 95% Cl 2.138-15.23, p = 0.001). CONCLUSIONS: Our study shows that most of severe symptoms of depression were present in 20% of the IBD patients examined who were receiving intravenous biological therapy. Particular attention and efforts should, therefore, be focused on patients who have an active form of the disease.

Acute hemolytic transfusion reaction caused by anti-Yta.

Many patients with anti-Yta receive multiple transfusions of Yt(a+) red blood cells (RBCs) with no ill effects. However, anti-Yta has been implicated in hemolytic transfusion reactions. Antibody identification typically determines specificity of antibodies and their clinical significance to justify blood requirements for antigen-negative blood when clinically significant antibodies are involved. Occasionally, specificity of antibody is of variable significance. Variability in clinical significance is a characteristic of anti-Yta that may affect the clinical management of such patients. This case reports the outcome of an incompatible transfusion in an 83-year-old female patient with anti-Yta, -D, -C, -Leab, and -HI who was admitted to the hospital for a severe urinary tract hemorrhage and fever. The patient was transfused with 1 crossmatch-incompatible group A, Yt(a+), D-, C-, E-, S- RBC unit in an emergency medical event. During that time, the patient exhibited chills, shivering, and tachycardia. Decreases in hemoglobin and hematocrit were noted. Laboratory parameters for hemolysis, such as total bilirubin, direct bilirubin, and lactate dehydrogenase, were increased. Based on clinical and laboratory evaluation, it was concluded that the patient had an acute hemolytic transfusion reaction caused by anti-Yta. The patient was successfully treated with antipyretics, antihistamines, and corticosteroids. Urinary tract hemorrhaging was stopped. Anemia was additionally improved with parenteral iron supplementation, and further transfusion was not required. Immunohematology 2021;37:13-17.Many patients with anti-Yta receive multiple transfusions of Yt(a+) red blood cells (RBCs) with no ill effects. However, anti-Yta has been implicated in hemolytic transfusion reactions. Antibody identification typically determines specificity of antibodies and their clinical significance to justify blood requirements for antigen-negative blood when clinically significant antibodies are involved. Occasionally, specificity of antibody is of variable significance. Variability in clinical significance is a characteristic of anti-Yta that may affect the clinical management of such patients. This case reports the outcome of an incompatible transfusion in an 83-year-old female patient with anti-Yta, -D, -C, -Leab, and -HI who was admitted to the hospital for a severe urinary tract hemorrhage and fever. The patient was transfused with 1 crossmatch-incompatible group A, Yt(a+), D­, C­, E­, S­ RBC unit in an emergency medical event. During that time, the patient exhibited chills, shivering, and tachycardia. Decreases in hemoglobin and hematocrit were noted. Laboratory parameters for hemolysis, such as total bilirubin, direct bilirubin, and lactate dehydrogenase, were increased. Based on clinical and laboratory evaluation, it was concluded that the patient had an acute hemolytic transfusion reaction caused by anti-Yta. The patient was successfully treated with antipyretics, antihistamines, and corticosteroids. Urinary tract hemorrhaging was stopped. Anemia was additionally improved with parenteral iron supplementation, and further transfusion was not required. Immunohematology 2021;37:13­17.

Reinforcement of barrier function - skin repair formulations to deliver physiological lipids into skin.

OBJECTIVE: The aim of the study was to develop formulations to deliver physiological lipids into skin in an attempt to repair defective barrier function. METHODS: Physiological cholesterol and linoleic acid were incorporated into basic cream and non-ionic cream to prepare skin repair formulations. Homogeneity and storage stability of the developed creams were examined by polarized light microscopy. Ex vivo evaluation was conducted using lipid-deficient skin samples and confocal Raman microspectroscopy. A 7-day in vivo study was performed on volunteers to study the repairing efficacy. RESULTS: Homogeneous texture was seen in the prepared skin repair formulations. The application of the creams led to substantially increased lipid levels compared to the reference in the lipid-deficient skin in ex vivo study. Twice-a-day application of the skin repair creams provided a reinforcement of the skin barrier as transepidermal water loss (TEWL) was significantly decreased. CONCLUSION: The skin repair creams showed excellent efficacy in skin recovery. They have great potentials for treating impaired skin barrier associated with depletion of lipids in stratum corneum.

Brain structural and functional signatures of impulsive-compulsive behaviours in Parkinson's disease.

This study assessed brain structural and functional alterations in patients with Parkinson's disease and impulsive-compulsive behaviours (PD-ICB) compared with controls and PD no-ICB cases. Eighty-five PD patients (35 PD-ICB) and 50 controls were recruited. All subjects underwent three-dimensional T1-weighted, diffusion tensor (DT), and resting state functional magnetic resonance imaging (RS fMRI). We assessed cortical thickness with surface-based morphometry, subcortical volumes using FIRST, DT MRI metrics using region of interest and tractography approaches, and RS fMRI using a model free approach. Compared with controls, both PD groups showed a pattern of brain structural alterations in the basal ganglia (more evident in PD no-ICB patients), sensorimotor and associative systems. Compared with PD no-ICB, PD-ICB cases showed left precentral and superior frontal cortical thinning, and motor and extramotor white matter tract damage. Compared with controls, all patients had an increased functional connectivity within the visual network. Additionally, PD no-ICB showed increased functional connectivity of bilateral precentral and postcentral gyri within the sensorimotor network compared with controls and PD-ICB. Severity and duration of PD-ICB modulated the functional connectivity between sensorimotor, visual and cognitive networks. Relative to PD no-ICB, PD-ICB patients were characterised by a more severe involvement of frontal, meso-limbic and motor circuits. These data suggest ICB in PD as the result of a disconnection between sensorimotor, associative and cognitive networks with increasing motor impairment, psychiatric symptoms, and ICB duration. These findings may have important implications in understanding the neural substrates underlying ICB in PD.

Serum parathyroid hormone is associated with increased cortical porosity of the inner transitional zone at the proximal femur in postmenopausal women: the Tromsø Study.

Serum parathyroid hormone (PTH) was associated with increased bone turnover markers and cortical porosity of the inner transitional zone at the proximal femur. These results suggest that PTH through increased intracortical bone turnover leads to trabecularisation of inner cortical bone in postmenopausal women. INTRODUCTION: Vitamin D deficiency leads to secondary hyperparathyroidism and increased risk for fractures, whereas its association with cortical porosity is less clear. We tested (i) whether serum 25-hydroxyvitamin D (25(OH)D) and PTH were associated with cortical porosity and (ii) whether the associations of 25(OH)D) and PTH with fracture risk are dependent on cortical porosity. METHODS: This case-control study included 211 postmenopausal women, 54-94 years old, with prevalent fractures and 232 controls from the Tromsø Study. Serum 25(OH)D, PTH, and bone turnover markers (procollagen type I N-terminal propeptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]) were measured. Femoral subtrochanteric cortical and trabecular parameters were quantified using computed tomography, and femoral neck areal bone mineral density (FN aBMD) was quantified using dual-energy X-ray absorptiometry. RESULTS: Compared with controls, fracture cases exhibited reduced serum 25(OH)D and increased PTH, PINP, and CTX, increased femoral subtrochanteric cortical porosity, and reduced cortical thickness and FN aBMD (all, p < 0.05). Serum 25(OH)D was not associated with cortical parameters (all, p > 0.10). PTH was associated with increased PINP, CTX, and cortical porosity of the inner transitional zone and reduced trabecular bone volume/tissue volume and FN aBMD (p ranging from 0.003 to 0.054). Decreasing 25(OH)D and increasing PTH were associated with increased odds for fractures, independent of age, height, weight, calcium supplementation, serum calcium, cortical porosity, and thickness. CONCLUSIONS: These data suggest that serum PTH, not 25(OH)D, is associated with increased intracortical bone turnover resulting in trabecularisation of the inner cortical bone; nevertheless, decreasing 25(OH)D) and increasing PTH are associated with fracture risk, independent of cortical porosity and thickness.

Towards satisfying performance of an O/W cosmetic emulsion: screening of reformulation factors on textural and rheological properties using general experimental design.

OBJECTIVE: Consumers' demand for improved products' performance, alongside with the obligation of meeting the safety and efficacy goals, presents a key reason for the reformulation, as well as a challenging task for formulators. Any change of the formulation, whether it is wanted - in order to innovate the product (new actives and raw materials) or necessary - due to, for example legislative changes (restriction of ingredients), ingredients market unavailability, new manufacturing equipment, may have a number of consequences, desired or otherwise. The aim of the study was to evaluate the influence of multiple factors - variations of the composition, manufacturing conditions and their interactions, on emulsion textural and rheological characteristics, applying the general experimental factorial design and, subsequently, to establish the approach that could replace, to some extent, certain expensive and time-consuming tests (e.g. certain sensory analysis), often required, partly or completely, after the reformulation. METHODS: An experimental design strategy was utilized to reveal the influence of reformulation factors (addition of new actives, preparation method change) on textural and rheological properties of cosmetic emulsions, especially those linked to certain sensorial attributes, and droplet size. RESULTS: The general experimental factorial design revealed a significant direct effect of each factor, as well as their interaction effects, on certain characteristics of the system and provided some valuable information necessary for fine-tuning reformulation conditions. Upon addition of STEM-liposomes, consistency, index of viscosity, firmness and cohesiveness were decreased, as along with certain rheology parameters (elastic and viscous modulus), whereas maximal and minimal apparent viscosities and droplet size were increased. The presence of an emollient (squalene) affected all the investigated parameters in a concentration-dependent manner. Modification of the preparation method (using Ultra Turrax instead of a propeller stirrer) produced emulsions with higher firmness and maximal apparent viscosity, but led to a decrease in minimal apparent viscosity, hysteresis loop area, all monitored parameters of oscillatory rheology and droplet size. CONCLUSION: The study showed that the established approach which combines a general experimental design and instrumental, rheological and textural measurements could be appropriate, more objective, repeatable and time and money-saving step towards developing cosmetic emulsions with satisfying, improved or unchanged, consumer-acceptable performance during the reformulation.

Transcranial brain sonography findings in two main variants of progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) can occur with two main clinical presentations, classified as classical Richardson's syndrome (PSP-RS) and as PSP-parkinsonism (PSP-P), the most common atypical PSP variant. The differential diagnosis between them is challenging. Therefore, we studied different ultrasound markers by transcranial sonography in individuals with PSP-RS and PSP-P, to test their value in the diagnostic work up of these patients. METHODS: Transcranial sonography was performed in 21 patients with PSP-RS and 11 patients with PSP-P. Echogenic sizes of the substantia nigra (SN) and the lenticular nuclei (LN), as well as the width of the third ventricle, were measured. RESULTS: Among the patients with PSP-RS and PSP-P, three (14%) and eight (73%) patients had a hyperechogenic SN (P = 0.020), respectively. Uni- or bilateral hyperechogenicity of the LN was observed in 67% and 36% of patients with PSP-RS and PSP-P, respectively (P = 0.101). Third ventricle was significantly wider in patients with PSP-RS (11.2 ±â€…2.3 mm) when compared with patients with PSP-P (7.5 ±â€…1.4 mm; P = 0.001). CONCLUSION: Our data, possibly reflecting pathological differences, primarily contribute supporting the view that the neurodegenerative process differs in the two PSP variants.

Lactobionic acid as antioxidant and moisturizing active in alkyl polyglucoside-based topical emulsions: the colloidal structure, stability and efficacy evaluation.

Cosmeceutical antioxidants may protect the skin against oxidative injury, involved in the pathogenesis of many skin disorders. However, an unsuitable topical delivery system with compromising safety profile can affect the efficacy of an antioxidant active. This study investigated the antioxidant potential of lactobionic acid (LA), a newer cosmeceutical active, per se (in solution) and incorporated into natural alkyl polyglucoside (APG) emulsifier-based system using 1,1-diphenyl-2-picrylhydrazyl free radical scavenging and lipid peroxidation inhibition assays. The α-tocopherol was used as a reference compound. The physical stability (using rheology, polarization microscopy, pH and conductivity measurements) of an Alkyl glucoside-based emulsion was evaluated with and without the active (LA); colloidal structure was assessed using polarization and transmission electron microscopy, rheology, thermal and texture analysis. Additionally, the safety profile and moisturizing potential were investigated using the methods of skin bioengineering. Good physical stability and applicative characteristics were obtained although LA strongly influenced the colloidal structure of the vehicle. LA per se and in APG-based emulsion showed satisfying antioxidant activity that promotes it as mild multifunctional cosmeceutical efficient in the treatment and prevention of the photoaged skin. Employed assays were shown as suitable for the antioxidant activity evaluation of LA in APG-based emulsions, but not for α-tocopherol in the same vehicle.

Pattern of brain tissue loss associated with freezing of gait in Parkinson disease.

OBJECTIVE: To investigate whether a specific pattern of gray matter (GM) tissue loss is associated with freezing of gait (FOG) in patients with Parkinson disease (PD). METHODS: Seventeen patients with PD with FOG (PD-FOG), 20 patients with PD with no FOG (PD-noFOG), and 34 healthy control subjects were recruited. PD-FOG and PD-noFOG patients were matched on an individual basis for age, disease duration, and Hoehn and Yahr stage. Patients were also administered a comprehensive neuropsychological battery focused on executive functions. The extent and distribution of GM atrophy were assessed using voxel-based morphometry. RESULTS: In patients with PD, the severity of FOG correlated with frontal executive deficits. Compared with healthy control subjects, PD-FOG patients showed a distributed pattern of GM atrophy including the dorsolateral prefrontal, medial, and lateral temporal, inferior parietal, and occipital cortices. PD-noFOG patients showed only small regions of GM atrophy in the bilateral frontal and temporal cortex. The left inferior frontal gyrus, left precentral gyrus, and left inferior parietal gyrus were more atrophic in PD-FOG patients relative to both healthy control subjects and PD-noFOG patients. In PD-FOG patients, the severity of FOG was associated with GM volumes of the frontal and parietal cortices bilaterally. CONCLUSIONS: GM frontal and parietal atrophy occur in PD-FOG patients. FOG in PD seems to share with executive dysfunction and perception deficits a common pattern of structural damage to the frontal and parietal cortices.

A combined approach in characterization of an effective w/o hand cream: the influence of emollient on textural, sensorial and in vivo skin performance.

To formulate a consumer-acceptable cosmetic product, numerous demands have to be fulfilled, and as the most important, efficacy (both real and perceived), adequate aesthetic (visual perception) and all sensorial characteristics have to be achieved. In this study, four model water-in-oil creams intended for hand care, varying in one emollient component, were submitted to rheological, sensory and textural characterization, and their efficacy was evaluated in in vivo study on human volunteers. Our results indicate that certain alteration restricted to the oil phase induced a change in all investigated characteristics, showing that each instrumental measurement can be used as a sensitive tool in the characterization of cream samples. Regarding the correlation between physical measurements and certain sensory attributes, it is possible to formulate a product with specific sensory characteristics by using pre-defined rheological or textural parameters. To obtain a complete sensory profile of a cosmetic product, a detailed sensory evaluation should be carried out according to the existing standard practices, which are both time- and money-consuming. However, a modified sensory study could be useful for fast in-line screening along with instrumental characterization of a novel cosmetic emulsion product and could be particularly helpful in the process of distinguishing a single formulation from several differing in one component.

Does lactobionic acid affect the colloidal structure and skin moisturizing potential of the alkyl polyglucoside-based emulsion systems?

Moisturizing creams are the most prescribed products in dermatology, essential in maintaining healthy skin as well as in the topical treatment of some diseases. The irritation potential of commonly used emulsifiers and moisturizing ingredients, but also their mutual interactions, could affect the functionality and safety of those dermopharmaceutics. The aim of this study was to promote moisturizing alkyl polyglucoside (APG)-based emulsion as vehicle for lactobionic acid (LA), advantageous representative of the alphahydroxyacids (AHAs)-multifunctional moisturizers, assessing the safety for use (in vitro acute skin irritation test using cytotoxicity assay compared with in vivo data obtained using skin bioengineering methods) and in vivo moisturizing capacity (bioengineering of the skin). In order to investigate possible interactions between APG mild natural emulsifier-based emulsion and LA, a deeper insight into the colloidal structure of the placebo and the emulsion with LA was given using polarization and transmission electron microscopy, rheology, thermal and texture analysis. This study showed that APG-based emulsions could be promoted as safe cosmetic/dermopharmaceutical vehicles and carriers for extremely acidic and hygroscopic AHA class of actives (specifically LA); prospective safety for human use of both APG and LA with the correlation between in vivo and in vitro findings was shown. However, it was revealed that LA strongly influenced the colloidal structure of the emulsion based on APGs and promoted the formation of lamellar structures which reflects onto the mode of water distribution within the cream. The advantageous skin hydrating potential of LA-containing emulsion vs. placebo was unlikely to be achieved, pointing that emulsions stabilized by lamellar liquid crystalline structures probably are not satisfying carriers for highly hygroscopic actives in order to reach the full moisturizing potential. Safe and effective use on dry skin is presumed.

Regional patterns of brain tissue loss associated with depression in Parkinson disease.

OBJECTIVE: To investigate, using MRI and voxel-based morphometry (VBM), whether specific patterns of gray matter (GM) and white matter (WM) loss are associated with depression in patients with Parkinson disease (PD). METHODS: Forty patients with PD and 26 healthy subjects were studied. Patients were diagnosed with depression using DSM-IV criteria. The Hamilton Depression Rating Scale (HDRS) was administered to patients. The topographic distribution of brain tissue loss in patients with PD and controls was assessed using VBM as implemented in Statistical Parametric Mapping (SPM5). RESULTS: Twenty-four patients with PD were diagnosed as nondepressed (PD-NDep) and 16 as having depression (PD-Dep). Patient groups were similar in terms of clinical findings, except for the HDRS score (p < 0.001). Compared to controls, patients with PD showed common GM loss in the right anterior cingulate (AC) cortex and insula, and in the left middle frontal and angular gyri (p < 0.001). No regions of WM loss common to PD-NDep and PD-Dep patients relative to healthy controls were found. PD-Dep vs PD-NDep patients showed WM loss in the right AC bundle and inferior orbitofrontal (OF) region (p < 0.001). In patients with PD, HDRS score correlated with WM loss in the right inferior OF region (r = -0.51, p < 0.05). CONCLUSIONS: Tissue loss in several WM regions within the cortical-limbic network occurs in PD-Dep vs PD-NDep patients. Such pattern of brain atrophy overlaps with key regions involved in major depressive disorders, suggesting an increased vulnerability of this neural circuit in PD. This may partially account for the high prevalence of depression in PD.

Inflammation at the interface of innate and acquired immunity.

This is the short summary of the presentation at the 2nd Belgrade Meeting on Immunoregulation entitled "Inflammation at the interface of Innate and Acquired Immunity" held recently under the auspice of European Federation of Immunological Societies and organized by Medical School, University of Kragujevac.

Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice.

Galectin 3 (Gal-3) is an antiapoptotic and a proinflammatory lectin. We hypothesized that the proinflammatory properties of Gal-3 may influence disease induction in the multiple low doses of streptozotocin model of diabetes. Diabetes was induced in C57BL/6 Gal-3(+/+) and Gal-3(-/-) mice and disease monitored by blood glucose level, immuno-histology, insulin content of islets and expression of the proinflammatory cytokines, TNF-alpha, IFN-gamma, IL-17, and iNOS in pancreatic lymph nodes. Gal-3(+/+) mice developed delayed and sustained hyperglycemia, mononuclear cellular infiltration and reduced insulin content of islets accompanied with expression of proinflammatory cytokines. Gal-3(-)/(-) mice were relatively resistant to diabetogenesis as evaluated by glycemia, quantitative histology and insulin content. Further, we observed the weaker expression of IFN-gamma and complete absence of TNF-alpha, and IL-17 in draining pancreatic lymph nodes. Macrophages, the first cells that infiltrate the islet in this model of diabetes, produce less TNF-alpha and NO in Gal-3(-/-) mice. Thus, Gal-3 is involved in immune mediated beta cell damage and is required for diabetogenesis in this model of disease.

Functional capacity of macrophages determines the induction of type 1 diabetes.

Macrophages are potent immune regulators and are critical in the development and pathogenesis of autoimmune diabetes. They are said to be the first cell type to infiltrate the pancreatic islet, serve as antigen-presenting cells, and are important as effector cells during diabetogenesis. The article examines the role of macrophages in autoimmune diabetes with particular emphasis on the role of galectin-3, a beta-galactoside-binding lectin, and T1/ST2, an IL-1 receptor-like protein, both of which play significant roles in the immunomodulatory functions of macrophages. Multiple low-dose streptozotocin (MLD-STZ) induces infiltration of mononuclear cells in the islets of susceptible strains leading to insulitis. Deletion of the galectin-3 gene from C57BL/6 mice significantly attenuates this effect as evaluated by quantitative histology of mononuclear cells and loss of insulin-producing beta cells. In contrast, deletion of the ST2 gene enhanced insulitis after MLD-STZ treatment when compared with relatively resistant wild-type BALB/c mice. Thus, it appears that functional capacity of macrophages influences their participation in T helper (Th) 1-mediated autoimmunity and the development of autoimmune diabetogenesis.

New members of the interleukin-12 family of cytokines: IL-23 and IL-27 modulate autoimmune diabetes.

Multiple low doses of streptozotocin (5 x 40 mg/kg) given to susceptible male C57BL6 mice induced delayed and sustained hyperglycemia accompanied by body weight loss, mononuclear cell infiltration in the islet, and apoptosis of beta cells. Shorter regimes (4 x 40 mg/kg) did not have such effect. Administration of IL-23 at a dose of 400 ng/mL for 10 consecutive days concomitantly with this subdiabetogenic regimen of STZ, however, induced significant hyperglycemia, weight loss, and mononuclear cellular infiltration. The same regimen of IL-27 induced milder effect on glycemia and no weight loss inspite of a massive peri-islet and intra-islet infiltration of mononuclear cells. The molecular mechanisms underlying the actions of these cytokines on diabetogenesis is under study.

Neuroglial response after induction of experimental allergic encephalomyelitis in susceptible and resistant rat strains.

Experimental allergic encephalomyelitis (EAE), the animal model for multiple sclerosis in humans, a T-cell mediated disease of the central nervous system is characterized by inflammatory infiltrates of myelin antigen(s)-specific T cells and consecutive demyelination. Spinal cord tissue emulsified in complete Freund's adjuvant clinical disease in the genetically susceptible Dark Agouti rats (DA) but not in Albino Oxford (AO) rats although similar inflammatory infiltrates in the CNS are observed in both strains 10-12 days after induction. We have shown that the resistance to clinical disease of AO rats is associated with rapid clearance of infiltrating mononuclear cells by a mechanism of apoptosis. Here, we demonstrate by immunohistochemical and FACS analyses of the expression of CD11b/c that microglial cells respond differently to disease induction in the two strains. Whereas microglial cells are activated throughout the period of day 10-28 days after EAE induction in AO rats they are only activated at the inception and resolution phases but not at the peak of clinical disease in DA rats when there is the highest level of CD4+ T cell infiltration. Our findings are compatible with the notion that microglia terminate effector T cells by apoptosis and that lack of this mechanism as evidenced by the lack of CD11b/c expression, support T cell survival and clinical expression of disease.