Characterization of highly pathogenic avian influenza H5N8 virus from Egyptian domestic waterfowl in 2017

In 2016, the highly pathogenic avian influenza (HPAI) H5N8 virus was detected in wild birds for the first time in Egypt. In the present study, we identified the HPAI virus H5N8 of clade 2.3.4.4 from domestic waterfowl in Egypt, suggesting its transmission to the domestic poultry from the migratory birds. Based on partial haemagglutinin gene sequence, this virus has a close genetic relationship with subtype H5N8 viruses circulating in Asia and Europe. Pathologically, H5N8 virus in hybrid duck induced nervous signs accompanied by encephalomalacia, haemorrhages, nonsuppurative encephalitis and nonsuppurative vasculitis. The granular layer of cerebellum showed multifocal areas of hydropic degeneration and the Purkinje cell neurons were necrotized or lost. Additionally, the lung, kidney and spleen were congested, and necrotizing pancreatitis was also observed. The co-circulation of both HPAI H5N1 and H5N8 subtypes with the low pathogenic avian influenza H9N2 subtype complicate the control of avian influenza in Egypt with the possibility of emergence of new reassortant viruses. Therefore, continuous monitoring with implementation of strict control measures is required.

Research highlights

• HPAI H5N8 virus clade 2.3.4.4 was detected in domestic ducks and geese in Egypt in 2017.

• Phylogenetically, the virus was closely related to HPAI H5N8 viruses identified in Asia and Europe

• Nonsuppurative encephalitis was widely observed in HPAI H5N8 virus-infected ducks.

• Degeneration of the cerebellar granular layer was found in most of the brain tissues examined.

     

A Psychoneuroendocrino-immune approach in the nursing treatment of anorexia and bulimia nervosa

Recent clinical reports have shown an increasing number of patients afflicted by eating disorders in the western world. There are numerous causes and mechanisms leading to eating disorders that affect the psychoneuroendocrinoimmune system. In this study, we define a novel psychoneuroendocrinoimmune nursing approach for anorexic and bulimic patients’ treatment. According to the specific diagnostic items deriving from the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases, and clinical guidelines in eating disorders formulated by the National Institute for Clinical Excellence, we carried out a qualitative study on the nursing treatment chosen by 210 international centers considered as a sample. This study was based on a no structured interview via e-mail to better understand the nursing approach in anorexia and bulimia nervosa. Thanks to the selected centers’ answers, four different levels of nursing care were identified, that include:

1. the nursing role analyzing the spectrum of patients’ problems;

2. the nursing intervention in inpatient care;

3. the nursing intervention in outpatient care;

4. the day hospital treatment.

All four prove to be especially useful in the nursing practice.     

Anethole reduces inflammation and joint damage in rats with adjuvant-induced arthritis

Aim

This study evaluated whether anethole attenuates the inflammatory response and joint damage in a model of adjuvant-induced arthritis (AIA) in rats.

Methods

The animals were treated with 62.5-, 125-, or 250-mg/kg anethole daily for 21 days after AIA and necropsied on days 14 and 21 to evaluate the number of serum and synovial leukocytes (total and differential), serum cytokines (IL-2, IL-6, IL-12, IL-17, and TNF-α), and nitric oxide concentrations. Morphologic changes in the cartilage and bone of the femorotibial articulation in both left paw and right paw were studied in hematoxylin/eosin and Sirius Red-hematoxylin sections.

Results

Different doses of anethole suppressed paw swelling and the number of serum and synovial leukocytes. However, 250 mg/kg of anethole more effectively controlled local and systemic inflammation. Histological evaluation revealed significant prevention of cartilage damage and inflammatory infiltrate scores. Morphometric analysis showed pannus formation, the thickness of the articular cartilage, and bone resorption lower in the anethole-treated AIA group compared to untreated AIA group on both days 14 and 21. These significant anti-inflammatory effects in the anethole-treated AIA group were associated with downregulation of cytokines and nitric oxide levels.

Conclusion

Therefore, anethole may be a useful intervention to treat inflammatory arthritis.

     

Autoimmunity

The following article has been retracted from publication in Autoimmunity:

1. “Drug-induced lupus erythematosus', Piercarlo Sarzi-Puttini, Fabiola Atzeni, Franco Capsoni, Ennio Lubrano & Andrea Doria., November 2005. Autoimmunity, 38:507–518.

This article has been found to reproduce content, without attribution or acknowledgement, from the following original articles:

• Antonov, D., Kazandjieva, J., Etugov, D., Gospodinov, D., Tsankov, N., (2004). Drug-induced Lupus Erythematosus. Clinics in Dermatology, 22, 157–166.

• Pramatov, K.D., (1998). Drug-induced Lupus Erythematosus. Clinics in Dermatology, 16, 367–377.

The Publishers wish to state that Autoimmunity published the article (1) in good faith, and on the basis of legal warranties made by the authors regarding the originality of their work. We welcome this opportunity to acknowledge and reinstate the rights of the original authors and the copyright of the original publishers.

We note that the authors of the above mentioned article (1) have submitted a written apology.     

Multilocus sequence typing of Campylobacter jejuni and Campylobacter coli to identify potential sources of colonization in commercial turkey farms

Poultry are the main reservoir for thermophilic Campylobacter spp., which is the most common causative agent of human bacterial gastroenteritis. The epidemiology of Campylobacter in poultry, particularly in turkeys, is not completely understood. This study aimed at identifying potential sources and transmission routes of thermophilic Campylobacter spp. in commercial turkey farms. C. jejuni and C. coli isolates from breeders (n?=?29, 20 C. jejuni and 9 C. coli) and their progeny (n?=?51, 18 C. jejuni and 33 C. coli) reared in two different farms for three sequential production cycles were analysed by multilocus sequence typing (MLST). Strains (n?=?88, 42 C. jejuni and 46 C. coli) isolated from environmental (i.e. anteroom and in-house overshoes), water (i.e. drinkers and water line), and pest (i.e. flies, Alphitobius diaperinus, and mice) sources were also examined. MLST of C. jejuni and C. coli isolates resulted in 13 and 12 different sequence types (STs) belonging to six and one previously-described clonal complexes (CCs), respectively. Three novel STs were identified. Genetic similarities were detected between isolates from fattening turkeys and the considered environmental, water, and pest sources, and with the breeders to a lesser extent. Source attribution analysis estimated that environmental and water sources accounted for most (～75%) of fattening turkey isolates and were therefore identified as the most likely sources of flock colonization, followed by pests (～20%) and breeders (～5%). These sources may thus be targeted by control measures to mitigate the risk of Campylobacter colonization in commercial turkeys.

RESEARCH HIGHLIGHTS

• High occurrence of C. jejuni and C. coli in commercial turkey flocks.

• High genetic diversity of C. jejuni and C. coli in commercial turkey flocks.

• Horizontal transmission responsible for Campylobacter colonization of commercial turkey flocks.

• Environmental and water sources involved in Campylobacter colonization of commercial turkey flocks.

• Strategies for prevention and control of Campylobacter colonization of commercial turkey flocks are needed.

     

Characterization of unilateral conjunctival inoculation with Mycoplasma gallisepticum in house finches

House finches in much of the continental United States experience annual epidemics of mycoplasmal conjunctivitis, caused by the bacterial pathogen Mycoplasma gallisepticum (MG). Although evidence suggests that natural infections typically begin unilaterally, experimental inoculations of songbirds with MG to date have all been administered bilaterally. Furthermore, studies of free-living finches find more severe clinical signs of mycoplasmal conjunctivitis in left versus right eyes, but the mechanisms underlying this side bias remain unknown. Here, we characterized unilateral inoculation of house finches with MG, and tested whether differential susceptibility of left versus right conjunctiva explains the side bias in disease severity of free-living finches. We directly inoculated house finches in either the left or right conjunctiva and characterized resulting disease severity and pathogen load throughout the course of infection. As expected, unilateral inoculation resulted in significantly more severe conjunctivitis, as well as higher conjunctival bacterial loads, on whichever side (left or right) birds were directly inoculated. However, in 55% of cases, unilateral inoculations resulted in bilateral disease, and in 85% cases there was evidence of bilateral infection. The overall severity of disease did not differ for birds inoculated in the left versus right conjunctiva, suggesting that physiological differences between the conjunctivae cannot explain the side bias in disease severity of free-living birds. Instead, laterality in exposure, perhaps due to feeding handedness, likely explains the detected field patterns.

RESEARCH HIGHLIGHTS

• House finches show more severe disease in the directly inoculated conjunctiva.

• Unilateral inoculations lead to high rates of bilateral infection and disease.

• Overall disease severity does not differ for the left- or right-inoculated conjunctiva.

• Laterality in exposure likely explains the left-side bias in natural infections.

     

In vitro phagocytosis of opsonized latex beads by HD11 cells as a method to assess the general opsonization potential of chicken serum

Opsonins, an important arm of the innate immune system, are various soluble proteins, which play a critical role in destruction of invading pathogens directly or via engulfment of pathogens through the intermediate of phagocytosis. The diversity of opsonin profiles is under genetic influence and may be associated with variation in disease resistance. The aim of this study was to set up an assay to determine serum opsonophagocytic potential (OPp) for chicken sera by flow cytometry and to evaluate the assay using samples from different chicken lines. Two chicken lines selected for high and low concentrations of mannose-binding lectin, a known opsonin, in serum were used to establish the method. Furthermore, the presumed “robust” Hellevad chickens and two other commercial chicken lines (Hisex and Bovans) were tested to evaluate OPp as a parameter reflecting general immune competence. The results showed that Hellevad and Bovans chickens had higher OPp than Hisex chickens. There were no correlations between concentrations of total IgY or mannose-binding lectin and OPp. However, a strong positive correlation was observed between vaccine-induced infectious bronchitis virus titres and OPp. Moreover, inverse relationships were observed between concentrations of total serum IgM as well as natural antibody levels, and OPp. In conclusion, in vitro opsonophagocytosis assessment and determination of OPp may be of relevance when addressing general innate immunocompetence.

RESEARCH HIGHLIGHTS

• A flow cytometry method was developed to assess poultry serum opsonophagocytosis potential.

• This method is based on serum-opsonin-coated polystyrene beads and HD11 cell phagocytosis.

• Serum samples from different commercial chicken lines were compared.

• Opsonophagocytic potential may be included in assay panels for general immune competence of poultry.

     

Therapeutic effect of acetazolamide,an aquaporin 1 inhibitor,on adjuvant-induced arthritis in rats by inhibiting NF-κB signal pathway

Objectives: Previous studies have shown that aquaporin 1 (AQP1) is up-regulated in synovium and cartilage of rheumatoid arthritis (RA) patients and that AQP1 may be involved in joint swelling and synovial inflammation. This study was aimed to investigate the potential therapeutic effect of acetazolamide (AZ, an AQP1 inhibitor) on rat adjuvant-induced arthritis (AIA) and explore its related mechanisms.

Materials and methods: Rat AIA was induced by complete Freund’s adjuvant. The effect of AZ on rat AIA was evaluated by secondary hind paw swelling, arthritis index, TNF-α and IL-1β serum levels and histological examination of ankle joint. Proteoglycans expression and mRNA levels of type-II collagen (COII) and aggrecan in cartilage were measured by alcian blue staining and real-time PCR, respectively. The protein levels of AQP1, IκBα, phospho-IκBα (p-IκBα), NF-κB p65 and phospho-NF-κB p65 (p-NF-κB p65) in synovial tissues were detected by western blot.

Results: AZ treatment could inhibit secondary hind paw swelling and arthritis index, reduce serum levels of TNF-α and IL-1β, and ameliorate pathological changes of ankle joint in AIA rats. AZ increased proteoglycans production and mRNA levels of COII and aggrecan in cartilage tissues. Moreover, AZ decreased AQP1 protein level and suppressed the activation of NF-κB pathway in synovium, indicated by inhibiting the degradation and phosphorylation of IκBα and reducing p-NF-κB p65 protein level.

Conclusions: AZ as an AQP1 inhibitor has a powerful therapeutic effect on rat AIA via inhibiting NF-κB activation, suggesting AQP1 inhibition might be of potential clinical interest in RA treatment.     

Macrophage migration inhibitory factor (MIF) inhibitor,Z-590 suppresses cartilage destruction in adjuvant-induced arthritis via inhibition of macrophage inflammatory activation

Background: Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory mediator that is involved in the progression of rheumatoid arthritis (RA). Previously, we demonstrated a small molecule compound 3-[(biphenyl-4-ylcarbonyl) carbamothioyl] amino benzoic acid (Z-590) could inhibit MIF activity with docking-based virtual screening and experimental evaluation.

Methods: The LPS activated RAW264.7 macrophage cells were used to determine the anti-inflammatory effects of Z-590 in vitro. A rat adjuvant-induced arthritis (AIA) model was used to determine the anti-arthritic effects of Z-590 in vivo.

Results: MIF inhibitor Z-590 significantly inhibited the production of NO, TNF-α and IL-6 in LPS-activated RAW 264.7 macrophage cells and markedly inhibited LPS-induced expression of TNF-α, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Z-590 also significantly reduced paw edema, serum level of TNF-α, IL-6 and spleen index in the adjuvant-induced arthritis (AIA) rat model. Furthermore, Z-590 markedly ameliorated joint inflammation and articular cartilage damage in AIA rat model.

Conclusion: MIF inhibitor Z-590 possesses potent anti-arthritic activity through suppression of macrophage activation, and could be a potential therapeutic treatment for RA.     

Structure and counter-transference in authentic movement from a Reichian analytic perspective

The aim of this article is to use my personal experience to identify the main characteristics of authentic movement focusing on the reasons why it is an effective therapeutic process. It includes:

• Some brief information on the discipline of authentic movement and on the Reichian theoretical model developed by Società Italiana di Analisi Reichiana (SIAR), which is the model used to analyse how authentic movement works

• Considerations on the “internal” and “external” elements in the setting. The internal element, the heart of the practice, is the facilitator or the therapist. External elements are the boundaries, the rules, and the containment-framework of authentic movement.

Regarding the facilitator's role, this paper will present a brief overview of the contributions of various authors on the theme of counter-transference and discuss how, when counter-transference is described in physical terms, it becomes a means of making the therapeutic process effective.

In my examination of authentic movement I concentrate more on the aspects of setting and bodily counter-transference rather than on the contents which surface during group work. In my opinion, the true strength of authentic movement lies in it's setting, which provides both first and second-field containment. The presence of both forms of containment supports effective therapeutic processes both individually and in a group.     

Inhibitory effects of ZSTK474, a phosphatidylinositol 3-kinase inhibitor, on adjuvant-induced arthritis in rats

Objective

We examined the effects of ZSTK474, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on adjuvant-induced arthritis (AIA).

Methods

AIA was induced in Lewis rats by subcutaneous administration of Freund’s complete adjuvant at the base of the tail on day 0. ZSTK474 was orally administered once daily from day 10. The severity of AIA was assessed by measuring the hind paw volume. The number of lymphocytes in inguinal lymph nodes (ILN) was determined by flow cytometry. The in vitro effects of ZSTK474 on the cell proliferation, and the cytokines and prostaglandin E₂ (PGE₂) production were evaluated by BrdU method, ELISA and cytometric beads array.

Results

ZSTK474 ameliorated the progression of AIA. The temporary increases in the number of T cells in ILN, which occurred along with the appearance of arthritis, were inhibited in the ZSTK474-treated groups. In vitro studies revealed that ZSTK474 inhibited the production of IFNγ and IL-17 in concanavalin A-activated T cells. In vitro studies further revealed that ZSTK474 inhibited the proliferation and PGE₂ production by fibroblast-like synovial cells (FLS).

Conclusion

ZSTK474 demonstrated prophylactic efficacy in a rat model of rheumatoid arthritis (RA) through inhibition of T cell and FLS functions. It was suggested that the inhibitors of PI3K have therapeutic potential for RA.     

Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation

Background

Human adipose tissue is an ideal autologous source of mesenchymal stem cells (MSCs) for various regenerative medicine and tissue engineering strategies. Aged patients are one of the primary target populations for many promising applications. It has long been known that advanced age is negatively correlated with an organism’s reparative and regenerative potential, but little and conflicting information is available about the effects of age on the quality of human adipose tissue derived MSCs (hAT-MSCs).

Methods

To study the influence of age, the expansion and in vitro differentiation potential of hAT-MSCs from young (<30 years), adult (35-50 years) and aged (>60 years) individuals were investigated. MSCs were characterized for expression of the genes p16^INK4a and p21 along with measurements of population doublings (PD), superoxide dismutase (SOD) activity, cellular senescence and differentiation potential.

Results

Aged MSCs displayed senescent features when compared with cells isolated from young donors, concomitant with reduced viability and proliferation. These features were also associated with significantly reduced differentiation potential in aged MSCs compared to young MSCs.

Conclusions

In conclusion, advancing age negatively impacts stem cell function and such age related alterations may be detrimental for successful stem cell therapies.     

Interleukin-9 Is Required for Allergic Airway Inflammation Mediated by the Cytokine TSLP

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Highlights? TSLP induces IL-9 from human and mouse Th9 cells ? TSLP enhances Th9-mediated allergic lung inflammation ? Blocking IL-9 attenuates TSLP-induced lung inflammation     

The effect of a commercial competitive exclusion product on the selection of enrofloxacin resistance in commensal E. coli in broilers

The effect of a competitive exclusion product (Aviguard®) on the selection of fluoroquinolone resistance in poultry was assessed in vivo in the absence or presence of fluoroquinolone treatment.

Two experiments using a controlled seeder-sentinel animal model (2 seeders: 4 sentinels per group) with one-day-old chicks were used. For both experiments, as soon as the chicks were hatched, the birds of two groups were administered Aviguard® and two groups were left untreated. Three days later, all groups were inoculated with an enrofloxacin-susceptible commensal E. coli strain. Five days after hatching, two birds per group were inoculated with either a bacteriologically fit or a bacteriologically non-fit enrofloxacin-resistant commensal E. coli strain. In experiment 2, all groups were orally treated for three consecutive days (days 8–10) with enrofloxacin. Throughout the experiments, faecal excretion of all inoculated E. coli strains was determined on days 2, 5, 8, 11, 18 and 23 by selective plating (via spiral plater). Linear mixed models were used to assess the effect of Aviguard® on the selection of fluoroquinolone resistance.

The use of Aviguard® (P?E. coli when no enrofloxacin treatment was administered. However, this beneficial effect disappeared (P?=?0.37) when the birds were treated with enrofloxacin. Similarly, bacterial fitness of the enrofloxacin-resistant E. coli strain used for inoculation had an effect (P?P?=?0.70).

Thus, enrofloxacin treatment cancelled the beneficial effects from administrating Aviguard® in one-day-old broiler chicks and resulted in an enrofloxacin-resistant flora.

RESEARCH HIGHLIGHTS

• The effect of Aviguard® on the selection of enrofloxacin resistance was assessed in vivo.

• Without enrofloxacin, Aviguard® reduced the selection of enrofloxacin resistance.

• When enrofloxacin was administered, it cancelled the beneficial effect of Aviguard®.

     

Validation of the Fitbit One,Garmin Vivofit and Jawbone UP activity tracker in estimation of energy expenditure during treadmill walking and running

Objectives: To determine the validity of energy expenditure estimation made by the Fitbit One, Garmin Vivofit and Jawbone UP activity trackers during treadmill walking and running. Determining validity of such trackers will inform the interpretation of the data they generate.

Design: Cross-sectional study.

Method: Fourteen adults walked at 0.70, 1.25, 1.80?ms^?1 and ran at 2.22, 2.78, 3.33?ms^?1 on a treadmill wearing a Fitbit One, Garmin Vivofit and Jawbone UP. Estimation of energy expenditure from each tracker was compared to measurement from indirect calorimetry (criterion). Paired t-tests, correlation coefficients and Bland–Altman plots assessed agreement and proportional bias. Mean percentage difference assessed magnitude of difference between estimated and criterion energy expenditure for each speed.

Results: Energy expenditure estimates from the Fitbit One and Garmin Vivofit correlated significantly (pr=?0.702; 0.854) with criterion across all gait speeds (0.70–3.33?ms^?1). Fitbit One, Garmin Vivofit and Jawbone UP correlated significantly (p?r?=?0.729; 0.711; 0.591) with criterion across all walking speeds (0.70–1.80?ms^?1). However, only the Garmin Vivofit correlated significantly (pr?=?0.346) with energy expenditure estimations from criterion across running speeds (2.22–3.33?ms^?1). Bland–Altman plots showed proportional bias for the Fitbit One and Garmin Vivofit. Energy expenditure estimations of single speeds were overestimated by the Fitbit One and underestimated by the Garmin Vivofit.

Conclusions: Energy expenditure reported by the devices distinguished between walking and running, with a general increase as exercise intensity increased. However, the reported energy expenditure from these devices should be interpreted with caution, given their potential bias and error.

• Practical implications

• Although devices report the same outcome of EE estimation, they are not equivalent to each other and differ from criterion measurements during walking and running.

• These devices are not suitable as research measurement tools for recording precise and accurate EE estimates but may be suitable for use in interventions of behaviour change as they provide feedback to user on trends in energy expenditure.

• If intending to use these devices in studies where precise measurements of energy expenditure are required, researchers need to undertake specific validation and reliability studies prior to interventions and the collection of cross-sectional data.

     

Decreased arthritis severity in cathepsin L-deficient mice is attributed to an impaired T helper cell compartment

Objective

Cathepsin L (CL) is potentially involved in joint destruction and in antigen presentation in rheumatoid arthritis. In order to define the roles of this protease in arthritis development we analysed the antigen-induced arthritis (AIA) in CL-deficient (CL^?/?) mice.

Methods

Antigen-induced arthritis was induced in CL^?/? and wild-type mice. Complete CL deficiency resulted in an impaired positive selection of conventional CD4⁺ T helper (Th) cells and finally in a reduced number of Th cells. Thus, we addressed the effect of this phenotype by rescuing CD4⁺ Th cell numbers by transgenic expression of the human CL-like protease cathepsin V (hCV) in thymic epithelium of CL^?/? mice [Tg(K14-hCV);CL^?/?]. The arthritis development was monitored by measuring joint swelling. Joint inflammation and destruction were assessed histopathologically.

Results

The severity of AIA was decreased in CL^?/? mice characterized by reduced swelling, decreased inflammation and destruction, and diminished cellular and humoral immune responsiveness. AIA in Tg(K14-hCV);CL^?/? mice was associated with a reconstitution of all parameters by normalization of the ratio of regulatory to conventional T cells.

Conclusions

Cathepsin L has a significant impact on AIA severity by influencing the selection of Th cell populations in the thymus, but seems not play any significant role in the direct joint destruction.     

A Promising Tool in Retina Regeneration: Current Perspectives and Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary and Human Ophthalmological Applications

Visual impairment is a common ailment of the current world population, with more exposure to CCD screens and fluorescent lighting, approximately 285 billion people suffer from this deficiency and 13% of those are considered clinically blind. More common causes for visual impairment include age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (Zhu et al. Molecular Medicine Reports, 2015; Kolb et al. 2007; Machalińska et al. Current Eye Research, 34(9),748–760, 2009) among a few. As cases of retinal and optic nerve diseases rise, it is vital to find a treatment, which has led to investigation of the therapeutic potential of various stem cells types (Bull et al. Investigative Opthalmology & Visual Science, 50(9), 4244, 2009; Bull et al. Investigative Opthalmology & Visual Science, 49(8), 3449, 2008; Yu et al. Biochemical and Biophysical Research Communications, 344(4), 1071-1079, 2006; Na et al. Graefe's Archive for Clinical and Experimental Ophthalmology, 247(4), 503-514, 2008). In previous studies, some of the stem cell variants used include human Muller SCs and bone marrow derived SCs. Some of the regenerative potential characteristics of mesenchymal progenitor stem cells (MSCs) include their multilineage differentiation potential, their immunomodulatory effects, their high proliferative activity, they can be easily cultured in vitro, and finally their potential to synthesize and secrete membrane derived vesicles rich in growth factors, mRNA and miRNA which possibly aid in regulation of tissue damage regeneration. These facts alone, explain why MSCs are so widely used in clinical trials, 350 up to date (Switonski, Reproductive Biology, 14(1), 44–50, 2014). Animal studies have demonstrated that sub-retinal transplantation of MSCs delays retinal degeneration and preserves retinal function through trophic response (Inoue et al. Experimental Eye Research, 85(2), 234–241, 2007). Umbilical cord derived MSCs (UC/MSCs) have also been shown to contain neuroprotective features of ganglion cells in rat studies (Zwart et al. Experimental Neurology, 216(2), 439–448, 2009). This review aims to present current MSC therapies in practice, as well as their retinal regeneration potential in animal models, and their innovative prospects for treatment of human retinal diseases.     

Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model

Objective and design

Mesenchymal stem cells (MSCs) are potent modulators of immune responses. Sepsis is the association of a systemic inflammatory response with an infection. The aim of this study was to test the ability of MSCs derived from adipose tissue, which have immunomodulatory effects, and to inhibit the septic process in an experimental model of mice.

Methods

Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10⁶ cells/animal).

Results

In the control group, there were no deaths; in the untreated septic group, the mortality rate was 100 % within 26 h; in the septic group treated with MSCs, the mortality rate reached 40 % within 26 h. The group treated with MSCs was able to reduce the markers of tissue damage in the liver and pancreas. The treated group had a reduction of inflammatory markers. Furthermore, the MSCs-treated group was able to inhibit the increase of apoptosis in splenocytes observed in the untreated septic group.

Conclusions

Our data showed that MSCs ameliorated the immune response with decrease of inflammatory cytokines and increase anti-inflammatory IL-10; moreover, inhibited splenocytes apoptosis and, consequently, inhibited tissue damage during sepsis.     

Antiinflammatory,analgesic, and antipyretic activities of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazolo[3,4-d]pyrimidine-2-carboxylate (AA-2379), a novel non-acidic agent

The antiinflammatory, analgesic, and antipyretic activities of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazolo[3,4-d] pyrimidine-2-carboxylate (AA-2379), a novel nonacidic agent, were examined.

1. AA-2379 had a potent antiinflammatory activity; 3–25 mg/kg, p.o. of the compound inhibited rat carrageenin-, bradykinin-, trypsin-, formalin-, dextran-, and nystatin-induced paw edema; mouse traumatic edema; and rat croton oil pouch inflammation by about 30%. The compound at 25–50 mg/kg, p.o. also inhibited the vascular permeability induced by histamine, serotonin, and bradykinin.
2. AA-2379 had an analgesic activity; the ID₅₀ values in mouse phenylquinone-induced writhing were 10.1 mg/kg, p.o. and the compound at 12.5 mg/kg, p.o. inhibited dog urate arthritis.
3. AA-2379 at 3–10 mg/kg, p.o. showed antipyretic activity in febrile rats and rabbits.
4. AA-2379, at 500 mg/kg, p.o. was not ulcerogenic in rats.
5. These data show that AA-2379 is more active than non-acidic antiinflammatory agents, such as tiaramide and aminopyrine.