Penicillamine and auto-immunity:Relationship or coincidence?

Drug induced lupus is an established and recognised entity,and penicillamine is one of the drugs that induce it.But the uncertainty remains:Could penicillamine trigger autoimmunity in a broad-spectrum or in a particular way?

Use of endoscopic ultrasound for diagnosis of cholangiocarcinoma in auto-immune hepatitis

In this report, a patient was exposed to an herbal remedy for hypercholesterolemia. She became acutely jaundiced while taking the remedy and presented for medical care. Endoscopic ultrasound was utilized, and found a distal common bile duct mass. Endoscopic retrograde cholangiopancreatography guided bile duct biopsies revealed that the mass was cholangio-carcinoma (CCA). This case highlights a unique association between autoimmune hepatitis and CCA. It also highlights that EUS can be safely used in patients with cirrhosis to spare invasive evaluation such as exploratory laporotomy for diagnosis and staging of cholangio-carcinoma.

Challenges to associate early onset epilepsy with COVID-19 autoimmune encephalitis:A case

BACKGROUND Diagnosis of coronavirus disease 2019(COVID-19)-related neurological events in the pediatric population is challenging.Overlapping clinical picture of children with altered neurological state and inborn errors of metabolism,in addition to the frequency of asymptomatic COVID-19 cases,pose the main challenges for diagnosis.Diagnostic approaches to the onset post-COVID 19 subacute encephalopathy are still troublesome as seronegative autoimmune encephalitis(AIE)is reported.CASE SUMMARY A 27-mo-old boy was admitted for stormy refractory seizure of polymorphic semiology and altered mental status followed by various neuropsychiatric features that were suggestive of AIE.Brain magnetic resonance imaging and cerebrospinal fluid analysis were normal.Neither the immunological assessment,including viral serologies,antinuclear antibodies,autoimmune antibodies(NMDA,AMPA,CASPR2,LG11,GABARB,Hu,Yo,Ri,CV2,PNMA2,SOX1,Titin,amphiphysin,Recoverin),nor the metabolic assessment for lactate and pyruvate showed significant anomaly.Both positive history of COVID-19 infection and the findings of characteristic repetitive extreme delta brush played a key role in the diagnosis of COVID-19-related AIE.A remarkable improvement in the state of the child was noted after two pulse doses of intravenous Veinoglobulin and high dose of intravenous Corticosteroid.CONCLUSION Diagnostic biomarkers for AIE might aid effective treatment.

Revisiting miR-155 in intervertebral disc degeneration:Blood cell signature and local cell-free profiles

We unraveled the expression profiles of coding-noncoding RNAs in intervertebral disc degeneration(IDD).However,it remains elusive regarding miR-155 expression in peripheral blood mononuclear cells(PBMCs)and local extracellular space in IDD.The study aimed for investigating the miR-155 expression of PBMCs,extracellular miRNAs(ex-miRNAs)of human nucleus pulposus(NP)tissues,and morphological changes of cell death in the IDD process.Here,we harvested peripheral blood and NP samples from scoliosis and IDD patients as control and degenerative groups,respectively.Then standard Ficoll density-gradient centrifugation was used to isolate PBMCs.The two subpopulations of PBMCs were divided based on the cellular difference in adherence,i.e.,monocytes/macrophages and lymphocytes.Quantitative real-time PCR was used to evaluate miR-155 relative expression in PBMCs.ex-miRNAs were screened by comparison between GSE19943,GSE63492,and extracellular RNA(exRNA)atlas.The morphological changes of cell death subtypes in IDD were observed in transmission electron microscopy(TEM).Results indicate that the lower expression of miR-155 in PBMCs from IDD patients ascribed to alterations in monocytes/macrophages.Moreover,we identified 594 shared hsa-miRNAs as the intracellular miRNA expression profile and 258 miRNAs as the ex-miRNA expression profile in human NP tissue.miR-155 was amongst intracellular miRNAs in NP.TEM observation presented multiple endocytic secretory vesicles within human NP cells,implicating exosome transporting machinery.Typical necroptosis and pyroptosis were noted in human NP.Collectively,this study reveals miR-155 expression in PBMCs from IDD patients.Moreover,we propose ex-miRNA expression profile and necroptosis/pyroptosis in human NP tissue,shedding novel light on the etiology of IDD.

Enterovirus and type 1 diabetes: What is the matter?

A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus(T1DM) establishment. Environmental factors may initiate and possibly sustain, accelerate, or retard damage to β-cells. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of human enterovirus in the pathogenesis of T1 DM. The genetic risk of T1 DM and particular innate and acquired immune responses to enterovirus infection contribute to a tolerance to T1DM-related autoantigens. However, the frequency, mechanisms, and pathways of virally induced autoimmunity and β-cell destruction in T1 DM remain to be determined. It is difficult to investigate the role of enterovirus infection in T1 DM because of several concomitant mechanisms by which the virus damages pancreatic β-cells, which, consequently, may lead to T1 DM establishment. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective.

Hepatocellular carcinoma with chronic B-type hepatitis complicated by autoimmune hemolytic anemia:A case report

A 57-year-old man consulted a local hospital because of a persistent slight fever. At the age of 37 years he was diagnosed having B-type hepatitis, but left the liver dysfunction untreated. Twenty years later, he was diagnosed having chronic hepatitis B, hepatocellular carcinoma （HCC） and macrocytic anemia, and referred to our hospital for further investigation. A HCC with a maximum diameter of 5.2 cm was detected in segment 8. Results of blood tests included 1.8 mg/dL serum total bilirubin, 0.9 mg/dL bilirubin, less than 10 mg/dL haptoglobin, 7.9 g/dL hemoglobin, 130 fL MCV, and 14.5% reticuloo/tes. A bone marrow sample showed erythroid hyperplasia. The direct Coombs test gave a positive result. We diagnosed the anemia as autoimmmune hemolytic anemia （AIHA）, for which prednisolone could not be administered due to positivity for HBsAg and HBeAg. After preparation of washed blood cells for later transfusion, the patient underwent systematic resection of segment 8. The cut surface of the resected specimen demonstrated an encapsulated yellow-brownish tumor measuring 52 mmx 40 mm which was diagnosed pathologicaly as moderately differentiated HCC. On the 9th postoperative day, the patient＇s temperature rose to 38℃, and exacerbated hemolysis was observed. The maximum total bilirubin value was 5.8 mg/dL and minimum hemoglobin level was 4.6 g/dL. He tolerated this period without blood transfusion. Currently he is being followed up as an outpatient, and shows no signs of HCC recurrence or symptoms of anemia. AIHA associated with HBV infection has been described in only three previous cases, and the present case is the first in which surgery was performed for accompanying HCC.

Utilization of kinase inhibitors as novel therapeutic drug targets:A review

Kinase inhibitors are a significant and continuously developing division of target therapeutics.The drug discovery and improvement efforts have examined numerous attempts to target the signaling pathway of kinases.The Kinase inhibitors have been heralded as a game-changer in cancer treatment.For developing kinase inhibitors as a treatment for various non-malignant disorders like auto-immune diseases,is currently undergoing extensive research.It may be beneficial to investigate whether cell-specific kinase inhibitor administration enhances therapeutic efficacy and decreases adverse effects.The goal of the current review is to gain insight into the role of kinase inhibitors in facilitating effective target drug delivery for the treatment of various anti-inflammatory,auto-immune,and anticancer disorders.The aim of this review is also to shed light on drug discovery approaches for kinase inhibitors,their mode of action,and delivery approaches.The variation in the binding of kinases bestows different target approaches in drug design,which can be employed for designing the targeted molecules.Several target sites have been studied,exceeding the design of drugs for various diseases like cancer,Alzheimer’s,rheumatoid arthritis,etc.Diverse delivery approaches have also been studied for the targeted application of kinase inhibitors.

Recurrent Oxaliplatin-Induced Immune Hemolytic Anemia by Chemotherapy for Metastatic Colon Cancer: A Case Report

We report herein the case of a 55-year-old man who presented an acute hemolysis following a 6th cycle of FOLFOX regimen for a metastatic colorectal cancer;this patient had previously received 12 cycles in an adjuvant setting. He had presented attenuated signs during the previous cycle. This corresponded to an oxaliplatin-induced immune hemolytic anemia. This unfrequent side effect of oxaliplatin needs to be known in order to avoid severe complications.

New Erra with Auto-Haemotherapy

The active researchers, till now, did not find a curative treatment for many diseases threatening lives of the patients. Proper management and treatment for those patients can give them longer and healthier lives. Over the years, auto-haemotherapy has been used to treat illnesses and diseases such as： arterial circulatory disorders, autoimmune diseases as rheumatoid arthritis, gout, bronchitis, allergies, ache vulgaris, skin eczema, leg ulcers, chronic sinusitis, skin lesions, HIV infection, HCV, Lyme disease, connective tissue diseases, fibromyalgia, asthma, history of heart attack and fungal infections. It helps in cessation of smoking, treatment of drug and alcohol addiction, decreasing the appetite, losing weight in obese patients and speeding up the recovery after a long period of illness. It has also been used in combination with conventional cancer treatment. Auto-haemotherapy is a simple technique where the blood is drawn from a vein and re-injected into a muscle. The blood in the muscle works as a foreign body that will be rejected by the reticulo-endothelial system. It stimulates the immune system and the bone marrow to increase the production of macrophages which are the body＇s cleaners. The macrophages cleanse everything, they eliminate bacteria, viruses, cancerous cells called neoplastic cells, this is a spring cleaning, and they even eliminate fibrin which is a clotted blood. Auto-haemotherapy is a very powerful technique with a low cost. It requires a syringe and a physician who knows how to withdraw blood from a vein and straight away does an intra-muscular injection with this blood under aseptic condition which increases and stimulates the immune system. Minor auto-haemotherapy technique was applied to 176 patients suffering from different diseases such as： Type I diabetes mellitus, bronchial asthma, chronic sinusitis, allergic conjunctivitis, allergic rhinitis, skin problems （vesicles, eczema, ulcer）, finger nail problem （infection, paronychia）, acne vulgaris, gastro-intestinal tract problem, lactose intolerance, connective tissue disease, AFS （adrenal fatigue syndrome）~ myasthenia gravis, fibromyalgia, gout, generalized osteoarthritis, joint osteoarthritis, low back pain with MODIC changes Type 1 on MRI （with or without spinal canal stenosis）, auto-immune diseases （ankylosing spondylitis, rheumatoid arthritis）, and infectious vaginal discharge. Also it has been applied to patients in order to stop smoking, and to other patients in order to lose weight. Results showed that the patients suffering from the previous different diseases improved significantly after being treated with auto-haemotherapy. In addition, the heavy smokers were able to decrease dramatically the number of cigarettes they were smoking, and the obese patients were able to lose their weight and they had less appetite.

Pernicious Anemia Associated Autoimmune Diseases in a Sub Saharian African Internal Medicine Service

Introduction: Pernicious anemia is an autoimmune disease. It is characterized by the presence of an autoimmune atrophic gastritis and various autoantibodies that lead to a vitamin B12 deficiency responsible for a macrocytic anemia. It is frequently associated with other specific or non-organ- specific autoimmune diseases. We report six patients with pernicious anemia associated with other autoimmune diseases. Patients and Results: There were six patients (4 females/2 males), mean age of 39.67 years. In all cases it was found macrocytic anemia. The average Hb was 6.08 g/dl and the average MGV: 110.67 fl. Bone marrow aspiration was performed in all patients. Megaloblastosis compatible with a lack of vitamin B12 or folic acid was constant. Determination of serum vitamin B12 was low in all cases while folic acid levels were within standards. Immuno- logically it was found in all patients, a positivity of anti-intrinsic factor antibody and/or anti- parietal cells antibody at rates up to 67 times over normal ranges. Pernicious anemia was associated with autoimmune thyroid dysfunction in 4 patients. It was two cases of Hashimoto thyroiditis at hypothyroidic phase (high TSHus, thyréoperoxydase anti-antibody positive (over 10 N) in both cases and Graves’ disease in the two other cases. Pernicious anemia was associated with a syndrome of primary antiphospholipid antibody in a case. Furthermore pernicious anemia was found in a patient autoimmune type 1 diabetes with strongly positive anti -GAD antibodies and rheumatoid arthritis by retaining it in the diagnosis of multiple autoimmune syndrome. Conclusion: These cases illustrate the existence of the association of pernicious anemia with other autoimmune diseases in our context. This should encourage practitioners to seek hided autoimmune diseases when they consider the diagnosis of pernicious anemia.

Functions of NKG2D in CD8^(+) T cells: an opportunity for immunotherapy

Natural killer group 2 member D(NKG2D)is a type II transmembrane receptor.NKG2D is present on NK cells in both mice and humans,whereas it is constitutively expressed on CD8+T cells in humans but only expressed upon T-cell activation in mice.NKG2D is a promiscuous receptor that recognizes stress-induced surface ligands.In NK cells,NKG2D signaling is sufficient to unleash the killing response;in CD8+T cells,this requires concurrent activation of the T-cell receptor(TCR).In this case,the function of NKG2D is to authenticate the recognition of a stressed target and enhance TCR signaling.CD28 has been established as an archetype provider of costimulation during T-cell priming.It has become apparent,however,that signals from other costimulatory receptors,such as NKG2D,are required for optimal T-cell function outside the priming phase.This review will focus on the similarities and differences between NKG2D and CD28;less well-described characteristics of NKG2D,such as the potential role of NKG2D in CD8+T-cell memory formation,cancer immunity and autoimmunity;and the opportunities for targeting NKG2D in immunotherapy.