Online ISSN: 2515-8260

Issue 1,

Issue 1


Activation of IL5R and CRTH2 on Human Eosinophils Elicit a Similar Molecular Response and Reveal a Synergistic Effect

Virginie Sippel; Berengère Renault; Berengère Renault; Berengère Renault; Gabin M. Pierlot; Berengère Renault; Peter M. A. Groenen; Daniel S. Strasser

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 1-11

Eosinophils represent a key cell driving inflammatory processes in diseases such as asthma and eosinophilic esophagitis. The entire process of migration and activation of eosinophils is orchestrated by a myriad of molecules, among which interleukin 5 (IL5) plays a crucial role. Another receptor expressed on eosinophils is chemo-attractant receptor like expressed on Th2 cells (CRTH2). CRTH2 activation has a prominent role in stimulating Th2 and type 2 innate lymphoid cells to produce IL5 in disease tissue, but also induces eosinophils migration and adhesion. Prostaglandin D2 is the endogenous ligand of CRTH2, predominately released by activated mast cells, another key cell involved in eosinophilic diseases. Consequently, the IL5 and CRTH2 pathway are likely triggered simultaneously in eosinophils in disease tissue. Understanding the molecular effects of CRTH2 and IL5 receptor (IL5R) activated eosinophils might provide new insights for efficient eosinophils blocking. We performed gene expression profiling with isolated human eosinophils to compare the molecular signatures of CRTH2 and IL5R activation. The identified genes were confirmed using an orthogonal technology, and simultaneous IL5R and CRTH2 activation was investigated on the protein level. This study reveals that IL5R and CRTH2 activation trigger a similar molecular response in eosinophils with stronger IL5R effects. C-C chemokine ligand 2 was produced synergistically upon IL5R and CRTH2 stimulation and might contribute to monocyte and macrophage recruitment to disease tissue. The effect on C-C chemokine receptor 1 suggests that eosinophils maturation in the tissue might even occur in absence of IL5 via the CRTH2 pathway.

Subsiding of Dependent Oedema Following Chiropractic Adjustment for Discogenic Sciatica

Eric C. P. Chu; John T. H. Wong

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 12-15

Background: Subsiding of dependent oedema with chiropractic treatment for sciatica has not been described in the literature. Case presentation: A 40-year-old woman presented with unbearable sciatic nerve pain which restricted her in doing daily activities. She also had bilateral leg swelling for some time and no apparent physical causes could be found after being reviewed by a cardiologist. The patient subsequently sought chiropractic care to relieve her pain. She unexpectedly experienced a beneficial outcome from spinal adjustment in which both sciatic nerve pain and leg oedema were simultaneously resolved. It is reasonable to say that ease of mobility from pain relief and increased lymphatic return from sympathetic responses can help eliminating leg oedema following spinal adjustment. Conclusions: The pathophysiology of oedema formation is multifactorial and the therapeutic role of chiropractic remains inconclusive in this case. Further researches are need in this area before the integration of chiropractic into cardiovascular practice.

Acquired Angioedema of the Glottis, Larynx and Neck in a Patient Affected by SLE: Case Report

S. Scollo; G. La Camera; S. Neri; C. Grasso; R. Cubisino; C. Bonsignore; V. La Rosa; M. Astuto

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 16-19

Acquired angioedema is a rare complication of systemic lupus erythematosus (SLE). It is generally secondary to C1 inhibitor deficiency due to antibody formation directed against the C1 inhibitor molecule. Face, mouth, tongue, lips, extremities and genitalia are generally involved but also respiratory and gastrointestinal mucosa may be affected. We report a case of a young woman with SLE who presented a severe airway obstruction caused by angioedema. We discuss her diagnostic and therapeutic management including a review of the literature.

Dolutegravir, Second Generation Integrase Inhibitor: A New Hope for HIV Patient

Geeta Yadav; Piyush Kumar; Yugal Kumar; Pradeep Kumar Singh

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 20-29

Undeterred efforts are reported and still continue in future to achieve the goals of virologic suppression in HIV-infected individuals. Dolutegravir is the result of all the efforts made in this direction. It is a recent integrase inhibitor drug approved by the US FDA (Food and Drug Administration) for use in the treatment-naïve and treatment-experienced HIV-infected patients. This article has reviewed all the aspects of the drug, including the structural and functional analyses, in vitro activity, pharmacokinetics, drug-drug interactions, MOA, metabolism, excretion, dosing/adverse effects and resistance profile. Dolutegravir is a potent and well tolerated antiretroviral agent that can play an important role in the treating patients harboring resistance to other antiretrovirals. Some new combinations of drug with other antiretrovirals are also in the pipeline that can increase the immunologic response of the HIV patients.

Efficacy of Intra-Articular Injection of Platelet Rich Plasma and Hyaluronic Acid in Early Knee Osteoarthritis – Case Series

Krishnaiah Kurapati; Sanjay Tapadia; Madhusudhan Rao; Kavitha Anbarasu; Vinod Kumar Verma; Syed Sultan Beevi

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 30-36

Higher prevalence and growing burden of knee Osteoarthritis (OA) combined with recent safety concerns about pharmacological interventions has increased demand for new effective technologies for its management. Need of the hour is an innovative treatment alternative which may repair cartilage damage rather than just reduce symptoms of pain. Hyaluronic acid (HA) and PRP has been shown to relieve pain and symptoms as well as slow the progression of disease as stand-alone therapy. Treatment combining these modalities could be particularly hopeful owing to their positive and diverse interaction among themselves. Combinational treatment using both PRP and HA was performed on a series of 12 patients with early stage primary knee OA who fulfilled all the designated inclusion and exclusion criteria. All the patients were evaluated before and after treatment (1, 3, 6 and 12 months) by physical examination, assessment of VAS for pain, WOMAC, IKDC, KOOS and OKS to record the patient-reported improvement in pain, functionality and quality of life (QOL). 2-tailed Mann Whitney U Test was performed to assess the effect of treatment at different follow-up times of all the clinical scores. Whereas, Pearson correlation coefficient was done to evaluate the correlation between different clinical scores. For all tests, p < 0.05 was considered significant. All patients showed statistically significant improvement in all orthopedics scores evaluated. VAS score was improved significantly from 3.00 ± 0.49 at baseline to 1.57 ± 0.41 (p = 0.031) in Grade I and 3.60 ± 0.51 at baseline to 2.10 ± 0.29 (p = 0.031) in Grade II patients at 6 months’ follow-up respectively. Other scores followed similar trends with statistically significant improvement at 6 months’ follow-up which maintained throughout till end of the study period. All patients treated experienced strong functional improvement and substantial gains in pain relief, functionality and QOL. Hence our preliminary findings suggest that combined PRP and HA procedure is safe and potentially efficacious, which merits further investigation in large clinical settings and also in controlled clinical trials with long-term follow-ups. Focal Points Bench side: Platelet Rich Plasma (PRP) deliver a large pool of signalling proteins including growth factors and cytokines to the local milieu driving the tissue regeneration and repair mechanisms which when combined with high molecular weight cross-linked hyaluronan could bestow greater viscoelastic properties and alleviate the symptoms of osteoarthritis. Bedside: Osteoarthritis (OA) is a chronic degenerative disease and there is no cure for OA except medical management and partial/total knee replacement in advanced stage. PRP along with HA could have the therapeutic potential to promote cartilage regeneration and inhibit inflammation synergistically by decreasing the friction coefficient and minimizing wear. Community: The burden of OA on quality of life, disability and health care utilization is quite high. Combined PRP and HA could be an effective single-dose treatment modality restoring the functional activities and considerably reducing effective cost of the treatment. Governments and regulatory agencies: The technology to obtain PRP is FDA-approved and its safety and efficacy has been well established through several clinical studies. Regulatory agencies should consider the evidences put forth by the researchers and sanction grants to investigate in larger clinical settings and also in controlled trials with different ethnicities with long-term follow-ups.

An Unusual Presentation of Systemic Lupus Erythematosus as Evan Syndrome: A Case Report and Review Literature

Ali Al Bshabshe; Hamdan Al-Shehri; Ali Assiri; Abdulmoneim Jamil

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 37-40

Evans syndrome is a rare autoimmune disorder with an unknown etiology. In this paper, we report the case of a 32-year-old Saudi woman living with Evans syndrome for more than 8 years (post-splenectomy) who was also diagnosed with systemic lupus erythematosus (SLE). She was admitted to our Hospital with severe headache and confusion due to cerebral venous thrombosis. The major hematologic manifestations of SLE were pancytopenia and the antiphospholipid syndrome, which are indicators of disease activity when all other possible causes are excluded. The patient was treated with anticoagulation and immunosuppressive therapy and subsequently showed significant improvements in thrombosis, thrombocytopenia, and anemia. This case report provides an overview of the association between Evan syndrome and SLE.

Leukemia Recurrence Exclusively in the Breast after Stem Cell Transplant

Naziya Samreen; Shahrukh K. Hashmi; Amy Lynn Conners; Asha Bhatt; Katrina N. Glazebrook

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 41-45

Introduction: Leukemic involvement of the breast is extremely rare but constitutes an oncologic emergency. Imaging findings of T-Cell acute lymphoblastic leukemia (T-ALL) recurrence in the breasts have not been previously described. Case Description: Patient is a 25 year old female who presented with symptoms of superior vena cava (SVC) obstruction secondary to a mediastinal mass status post biopsy demonstrating T-ALL, which was cluster of differentiation 3 (CD3) positive and B-cell lymphoma 2 (BCL-2), and 80% Ki-67 positive. She was treated with chemotherapy and post-treatment positron emission tomography/computed tomography (PET/CT) demonstrated resolution of mediastinal mass, with no evidence of distant disease. She underwent allogeneic hematopoietic stem cell transplant (HSCT) in first remission. Seven months post-HSCT, patient presented with a large area of tender swelling of both the breasts with biopsy demonstrating relapsed T-ALL. Radiologic findings showed bilateral breast masses on ultrasound and mammogram, which were hypermetabolic on PET/CT. Conclusions: Breast involvement in leukemia recurrence, a very rare entity, can present with palpable masses. Mammographic findings in leukemia can include masses or architectural distortion, they are typically hyperechoic on ultrasound, and can have marked uptake on PET/CT. Oncologists, primary care providers and radiologists should be aware of leukemia presentations in the breast for prompt referral for urgent management.

Arteriovenous Malformation Pulmonary (AVM) in a Post-Cesarean Woman: Intensive Care and Urgent Surgery Operation

Francesco Oliveri; Christian Bonsignore; Ilenia Musumeci; Paolo Murabito; Stefano Scollo; Valeria La Rosa; Alberto Terminella; Giacomo Cusumano; Vito Sofia; Marinella Astuto

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 46-50

The AVM is a rare congenital disease that often affects the brain and only rarely we find in other organs. In this pathology there is an alteration of the vascular system, with the arteries discharging directly into the veins, bypassing the capillary system; this puts the patient at high risk of sudden hemorrhage. Today we present the case of a young woman suffering from unknown pulmonary avm. The breakdown of this avm caused a hemothorax in the immediate post-cesarean, necessitating emergency surgery and subsequent intensive care.

Congress Abstracts: 2018-European Clinical Case Reports Congress (EUCCR-2018), 21–22 April 2018, Vienna, Austria

Aamir Shahzad; Randall J. Cohrs

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 51-84

Oral Abstracts First report of a case of central nervous system vasculitis associated to the use of the check point inhibitor ipilimumab Juan Maya, Florentina Berianu, Benjamin Wang, Andy Abril and Ronald R. Butendieck Jr. Mayo Clinic Florida, Jacksonville, US

Isolated Demyelination of Corpus Callosum Following Hypoxia

Lucio Marinelli; Lara Castelletti; Carlo Trompetto

European Journal of Molecular & Clinical Medicine, 2018, Volume 5, Issue 1, Pages 85-88

Corpus callosum includes a large amount of axons with various degrees of myelination, interconnecting cerebral hemispheres. Tumors, demyelinating diseases, infections, trauma and metabolic diseases as well as vascular lesions may affect corpus callosum, often extending to other white matter areas of the brain. We describe the case of a 76 years old male patient with history of arterial hypertension, diabetes mellitus and normal pressure hydrocephalus, developing dysphagia during hospitalization. Ab-ingestis pneumonia caused brain hypoxia and coma; brain magnetic resonance disclosed isolated demyelination of corpus callosum that was not present before hypoxia. Compared to neurons and astrocytes, oligodendrocytes are reported as particularly sensitive to hypoxia. Respiratory involvement without blood flow impairment could have lead to a prevalent oligodendrocytes damage, resulting in a selective demyelination of corpus callosum. Our patient indeed evolved into persistent vegetative state and died five months after hypoxic episode. This case report could give some insight about in vivo brain susceptibility to hypoxic damage.