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The Pan African Medical Journal 2018Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with... (Review)
Review
Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign macrophages exhibiting haemophagocytic activity. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish underlying disease flare, infectious complications or medication side effects from MAS. Although, the pathogenesis of MAS is unclear, the hallmark of the syndrome is an uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS in his secondary form. We present here a case of Macrophage activation syndrome associated with Griscelli syndrome type 2 in a 3-years-old boy who had been referred due to severe sepsis with non-remitting high fever, generalized lymphoadenopathy and hepato-splenomegaly. Laboratory data revealed pancytopenia with high concentrations of triglycerides, ferritin and lactic dehydrogenase while the bone marrow revealed numerous morphologically benign macrophages with haemophagocytic activity that comforting the diagnosis of a SAM according to Ravelli and HLH-2004 criteria. Griscelli syndrome (GS) was evoked on; consanguineous family, recurrent infection, very light silvery-gray color of the hair and eyebrows, Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. The molecular biology showed mutation in RAB27A gene confirming the diagnosis of a Griscelli syndrome type 2. The first-line therapy was based on the parenteral administration of high doses of corticosteroids, associated with immunosuppressive drugs, cyclosporine A and etoposide waiting for bone marrow transplantation (BMT).
Topics: Adrenal Cortex Hormones; Child, Preschool; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Male; Mutation; Piebaldism; Primary Immunodeficiency Diseases; Sepsis; rab27 GTP-Binding Proteins
PubMed: 29875956
DOI: 10.11604/pamj.2018.29.75.12353 -
JAAD Case Reports May 2018
PubMed: 29693058
DOI: 10.1016/j.jdcr.2017.10.005 -
ENeuro 2018Traumatic brain injury (TBI) leads to a deleterious and multifactorial secondary inflammatory response in the brain. Oxidative stress from the inflammation likely...
Traumatic brain injury (TBI) leads to a deleterious and multifactorial secondary inflammatory response in the brain. Oxidative stress from the inflammation likely contributes to the brain damage although it is unclear to which extent. A largely unexplored approach is to consider phenotypic regulation of oxidative stress levels. Genetic polymorphism influences inflammation in the central nervous system and it is possible that the antioxidative response differs between phenotypes and affects the severity of the secondary injury. We therefore compared the antioxidative response in inbred rat strains dark agouti (DA) to piebald viral glaxo (PVG). DA has high susceptibility to inflammatory challenges and PVG is protected. Primary neuronal cell cultures were exposed to peroxynitrite (ONOO), nitric oxide (NO), superoxide (O), and 4-hydroxynonenal (4-HNE). Our findings demonstrated a phenotypic control of the neuronal antioxidative response, specific to manganese O dismutase (MnSOD). DA neurons had increased levels of MnSOD, equal levels of peroxiredoxin 5 (PRDX5), decreased oxidative stress markers 3-nitrotyrosine (3-NT) and 4-HNE and decreased neuronal death detected by lactate dehydrogenase (LDH) release after 24 h, and higher oxidative stress levels by CellROX than PVG after 2 h. It is possible that DA neurons had a phenotypic adaptation to a fiercer inflammatory environment. ONOO was confirmed as the most powerful oxidative damage mediator, while 4-HNE caused few oxidative effects. Inducible NO synthase (iNOS) was not induced, suggesting that inflammatory, while not oxidative stimulation was required. These findings indicate that phenotypic antioxidative regulation affects the secondary inflammation, which should be considered in future individualized treatments and when evaluating antioxidative pharmacological interventions.
Topics: Animals; Brain Injuries, Traumatic; Cell Culture Techniques; Disease Models, Animal; Disease Susceptibility; Dopaminergic Neurons; Embryo, Mammalian; Hippocampus; Inflammation; Oxidative Stress; Rats; Rats, Inbred Strains
PubMed: 29568799
DOI: 10.1523/ENEURO.0335-17.2018 -
The Journal of Allergy and Clinical... Jul 2018
Topics: 5' Untranslated Regions; Adolescent; Child; Female; Humans; Immunologic Deficiency Syndromes; Lymphocytes; Lymphohistiocytosis, Hemophagocytic; Male; Melanocytes; Mutation; Pedigree; Piebaldism; Pigmentation; Primary Immunodeficiency Diseases; rab27 GTP-Binding Proteins
PubMed: 29522846
DOI: 10.1016/j.jaci.2018.02.031 -
Molecular Medicine Reports Apr 2018Tyrosinase‑related protein 2 (TRP‑2) is one of the most important members of the tyrosinase family, and is a key enzyme involved in melanin biosynthesis. In the...
Tyrosinase‑related protein 2 (TRP‑2) is one of the most important members of the tyrosinase family, and is a key enzyme involved in melanin biosynthesis. In the present study, a skin transcriptome profile, immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction were used to investigate TRP‑2 expression in sheep with different coat colors, namely, black, white and black‑white. TRP‑2 was overexpressed in melanocytes in order to study the effect of TRP‑2 on melanin production. Results revealed differing TRP‑2 levels in sheep of different coat colors and in various parts of the coat with different colors in the same sheep. TRP‑2 expression levels in dark‑colored areas were significantly increased compared with light‑colored areas in piebald sheep. TRP‑2 overexpression may regulate melanogenesis and significantly increase melanogenesis associated transcription factor expression in vitro. Therefore, TRP‑2 may affect melanin production in sheep, and different expression levels determine coat color. The results may provide novel approaches for developing therapeutic strategies for skin diseases associated with pigmentation disorders.
Topics: Animals; Gene Expression Profiling; Immunohistochemistry; Intramolecular Oxidoreductases; Melanins; Melanocytes; Sheep; Skin Pigmentation; Transcriptome
PubMed: 29436631
DOI: 10.3892/mmr.2018.8563 -
Annals of Dermatology Dec 2017
PubMed: 29200776
DOI: 10.5021/ad.2017.29.6.801 -
Molecules (Basel, Switzerland) Oct 2017Bombesin-like peptides, which were identified from a diversity of amphibian skin secretions, have been demonstrated to possess several biological functions such as...
Pharmacological Effects of Two Novel Bombesin-Like Peptides from the Skin Secretions of Chinese Piebald Odorous Frog (Odorrana schmackeri) and European Edible Frog (Pelophylax kl. esculentus) on Smooth Muscle.
Bombesin-like peptides, which were identified from a diversity of amphibian skin secretions, have been demonstrated to possess several biological functions such as stimulation of smooth muscle contraction and regulation of food intake. Here, we report two novel bombesin-like peptides, bombesin-OS and bombesin-PE, which were isolated from Odorrana schmackeri and Pelophylax kl. esculentus, respectively. The mature peptides were identified and structurally confirmed by high performance Scliquid chromatography (HPLC) and tandem mass spectrometry (MS/MS). Subsequently, the effects of these purified chemically-synthetic peptides on smooth muscle were determined in bladder, uterus, and ileum. The synthetic replications were revealed to have significant pharmacological effects on these tissues. The EC values of bombesin-OS for bladder, uterus and ileum, were 10.8 nM, 33.64 nM, and 12.29 nM, respectively. Furthermore, compared with bombesin-OS, bombesin-PE showed similar contractile activity on ileum smooth muscle and uterus smooth muscle, but had a higher potency on bladder smooth muscle. The EC value of bombesin-OS for bladder was around 1000-fold less than that of bombesin-PE. This suggests that bombesin-OS and bombesin-PE have unique binding properties to their receptors. The precursor of bombesin-OS was homologous with that of a bombesin-like peptide, odorranain-BLP-5, and bombesin-PE belongs to the ranatensin subfamily. We identified the structure of bombesin-OS and bombesin-PE, two homologues peptides whose actions may provide a further clue in the classification of ranid frogs, also in the provision of new drugs for human health.
Topics: Amino Acid Sequence; Animals; Base Sequence; Bombesin; Cloning, Molecular; Female; Ileum; Muscle Contraction; Muscle, Smooth; Peptide Fragments; Rana esculenta; Rats; Rats, Wistar; Sequence Homology; Skin; Urinary Bladder; Uterus
PubMed: 29065544
DOI: 10.3390/molecules22101798 -
The Pan African Medical Journal 2017Piebaldism is a rare autosomal dominant genodermatosis. It is due to congenital absence of melanocytes in the affected areas. We report a case. A 5 year old girl born to...
Piebaldism is a rare autosomal dominant genodermatosis. It is due to congenital absence of melanocytes in the affected areas. We report a case. A 5 year old girl born to consanguineous parents and with similar cases in her mother's; she presented since birth achromic lesions on the legs with a steady evolution. clinical examination showed confluent achromic macules and poliosis (A) with no contrast enhancement under Wood lamp and several coffee-with-milk colored spots on the trunk and thighs(B). The diagnosis of piebaldism was made. Piebaldism is a rare genodermatosis. Its incidence is estimated at less than 1/20000 newborns. It is characterized by the congenital absence of melanocytes in the areas affected by mutation of the c-kit gene and by symmetrical achromic macules appeared at birth with a steady and persistent evolution. A white lock of hair on the forehead could be seen in 80% of cases The differential diagnosis includes vitiligo, albinism and Waardenburg syndrome. Associations have been described with neurofibromatosis type I. However, isolated coffee-with-milk colored spots can be observed; as the case of our patient. The treatment is based on split-thickness skin graft. Piebaldism is a rare genodermatosis. This study aims to discuss its clinical aspects and differential diagnoses.
Topics: Child, Preschool; Diagnosis, Differential; Female; Humans; Melanocytes; Mutation; Piebaldism; Proto-Oncogene Proteins c-kit
PubMed: 28979623
DOI: 10.11604/pamj.2017.27.221.4961 -
Frontiers in Immunology 2017Transplant tolerance induced in adult animals is mediated by alloantigen-specific CD4CD25 T cells, yet in many models, proliferation of CD4 T cells from hosts tolerant...
Transplant tolerance induced in adult animals is mediated by alloantigen-specific CD4CD25 T cells, yet in many models, proliferation of CD4 T cells from hosts tolerant to specific-alloantigen is not impaired. To identify changes that may diagnose tolerance, changes in the patterns of proliferation of CD4, CD4CD25, and CD4CD25 T cells from DA rats tolerant to Piebald Virol Glaxo rat strain (PVG) cardiac allografts and from naïve DA rats were examined. Proliferation of CD4 T cells from both naïve and tolerant hosts was similar to both PVG and Lewis stimulator cells. In mixed lymphocyte culture to PVG, proliferation of naïve CD4CD25 T cells was greater than naïve CD4 T cells. In contrast, proliferation of CD4CD25 T cells from tolerant hosts to specific-donor PVG was not greater than CD4 T cells, whereas their response to Lewis and self-DA was greater than CD4 T cells. Paradoxically, CD4CD25 T cells from tolerant hosts did not proliferate to PVG, but did to Lewis, whereas naïve CD4CD25 T cells proliferate to both PVG and Lewis but not to self-DA. CD4CD25 T cells from tolerant, but not naïve hosts, expressed receptors for interferon (IFN)-γ and IL-5 and these cytokines promoted their proliferation to specific-alloantigen PVG but not to Lewis or self-DA. We identified several differences in the patterns of proliferation to specific-donor alloantigen between cells from tolerant and naïve hosts. Most relevant is that CD4CD25 T cells from tolerant hosts failed to proliferate or suppress to specific donor in the absence of either IFN-γ or IL-5. The proliferation to third-party and self of each cell population from tolerant and naïve hosts was similar and not affected by IFN-γ or IL-5. Our findings suggest CD4CD25 T cells that mediate transplant tolerance depend on IFN-γ or IL-5 from alloactivated Th1 and Th2 cells.
PubMed: 28878770
DOI: 10.3389/fimmu.2017.00994 -
International Journal of Women's... Sep 2017Genetic skin diseases encompass a vast, complex, and ever expanding field. Recognition of the features of these diseases is important to ascertain a correct diagnosis,... (Review)
Review
Genetic skin diseases encompass a vast, complex, and ever expanding field. Recognition of the features of these diseases is important to ascertain a correct diagnosis, initiate treatment, consider genetic counseling, and refer patients to specialists when the disease may impact other areas. Because genodermatoses may present with a vast array of features, it can be bewildering to memorize them. This manuscript will explain and depict some genetic skin diseases that occur in both humans and domestic animals and offer a connection and memorization aid for physicians. In addition, we will explore how animal diseases serve as a model to uncover the mechanisms of human disease. The genetic skin diseases we will review are pigmentary mosaicism, piebaldism, albinism, Griscelli syndrome, ectodermal dysplasias, Waardenburg syndrome, and mucinosis in both humans and domesticated animals.
PubMed: 28831430
DOI: 10.1016/j.ijwd.2017.01.003