Advances in the use of GABAergic interneurons for the treatment of epilepsy
Published on: 4th September, 2019
OCLC Number/Unique Identifier: 8333008407
Forebrain GABAergic neurons, the main inhibitory type of neuron in the cortex and hippocampus, represent a highly heterogeneous cell population that has been implicated in the predisposition to epilepsy and the onset of seizure. Earlier attempts to restore inhibition and reduce seizure in animal models of epilepsy have been carried out using embryonic basal forebrain tissue as source of immature GABAergic progenitors in cell-based therapies, with promising results. For therapeutic strategies this approach appears unrealistic, while the use of pluripotent stem cells to obtain immature GABAergic neurons opens new and promising avenues. Research on neural stem cells and pluripotent stem cells has greatly advanced and protocols have been established to efficiently direct progenitor cells to differentiate towards the GABAergic lineage. However, being highly heterogeneous, these neurons are difficult to be fully represented in vitro. Better knowledge on the expressed gene profiles, at single cell level, and the differentiation trajectory of these neurons will consent a more precise monitoring of the differentiation steps. Here we review the current literature about how to obtain and characterize genuine inhibitory neurons, how these can be grafted in animal models (and one day possibly in human) and which diseases could potentially be targeted and the efficiency of therapeutic outcome. The main obstacles that need to be overcome are: a) choice of an appropriate animal model, b) availability of human cells prone to GABA differentiation, c) the full representation of all IN subtypes, their proportions and their physiological activities, d) how to monitor them on the long-term after transplant.
Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation
Published on: 9th December, 2019
OCLC Number/Unique Identifier: 8440596237
Natural killer cells represent the first line of defense against infections and tumors and can be derived from various sources including: bone marrow, peripheral blood, specific types of human stem cells, and certain cell lines. The functions of natural killer cells are influenced by: several cytokines, activating and inhibitory receptors, as well as other immune cells such as dendritic cells and mesenchymal stem cells.
Natural killer cells are attractive candidates for adoptive cellular therapy in patients with hematologic malignancies and solid tumors in addition to recipients of various forms of hematopoietic stem cell transplantation as they enhance antitumor effects without causing graft versus host disease. Several clinical trials have shown safety and efficacy of natural killer cell products obtained from autologous as well as allogeneic sources and used in conjunction with cytotoxic chemotherapy, monoclonal antibodies and novel agents.
The following review, which includes extensive literature review on several aspects of natural killer cells, will give particular attention to: the rising role of natural killer cell therapies in patients with malignant hematological disorders, solid tumors and in recipients of stem cell therapies; preparation and manufacture of natural killer cell products; challenges facing the utilization of this form of cellular therapy including evolution of resistance; and maneuvers that can be employed to enhance the efficacy of natural killer cell therapies as well as suggested solutions to resolve the remaining challenges.
The rising role of mesenchymal stem cells in the treatment of COVID-19 infections
Published on: 7th July, 2020
OCLC Number/Unique Identifier: 8623431074
Infectious diseases are a leading cause of death worldwide [1,2]. The Mid-20th century witnessed most of the antimicrobial discoveries but recently there is dramatic shortage of new classes of antimicrobial agents due to failure to build a sustainable antimicrobial discovery platform [1-4]. For example, antibiotics comprise ˂ 1.5% of the compounds under investigation at the major pharmaceutical and biotechnology companies [1,5].
Transcriptional profile of bovine preimplantation development selected based on G6PDH activity
Published on: 8th April, 2021
OCLC Number/Unique Identifier: 9026744769
The oocyte is the female gamete that contributes not only half of the genetic material but also all of the cytoplasm to the zygote, supplying the transcripts, proteins, mitochondria and other components necessary for early embryonic development. The intrinsic oocyte quality is one of the main factors affecting the embryo yield, the implantation rate and the rate of healthy offspring. It is obvious that a fertilized oocyte must reach the blastocyst stage within 6–9 days in the proper culture conditions to have a significant chance of inducing a pregnancy and producing an offspring. The ability to sustain the first week of embryonic development is clearly influenced by the follicular status from which the oocyte is obtained indicating that this developmental potential is inherent within certain oocytes. Since most early embryos that do not reach the blastocyst stage are blocked at or close to the maternal to zygotic transition (MZT)-stage, which occurs at the eight-cell stage in cattle, one could speculate that incompetent oocytes fail to appropriately activate the embryonic genome. Oocyte selection based on glucose-6-phosphate dehydrogenase (G6PDH) activity has been successfully used to differentiate between competent and incompetent bovine oocytes. Recently, molecular regulation of genes regulating biological process of Brilliant Cresyl Blue staining (BCB) selected oocytes and embryos was investigated to explain their variation in quality and developmental potentiality. This short review will highlights some of these efforts that have been done in this interesting area of research.
Urine Leak Following Kidney Transplantation: An Evidence-based Management Plan
Published on: 2nd October, 2018
OCLC Number/Unique Identifier: 7869210591
Care of kidney transplant recipient remains complex and long-term graft survival is not seen in every transplant recipient. Due to reduced supply and increased demand of human organs, more transplants are carried out using marginal grafts on emergency lists. Transplant recipients have altered physiology due to known end-stage renal disease, recent surgery and the use of potent analgesic and immunosuppressive medications. Amongst the known surgical complications, urine leak remains the most common. It can result from poor graft preparation due to excessive peri ureteric or lower pole dissection or damage to lower polar artery resulting in ischemic necrosis. In addition, poor surgical technique, bladder outflow obstruction, iatrogenic injury to bladder or renal pelvis may contribute to urine leak. Ongoing urine leak may manifest itself as swelling, pain, high drain output, sepsis, ileus and eventual graft loss. Early identification, localisation and quantification of leak remain essential in management of these patients. In addition, sepsis should be identified and treated promptly as these patients are highly susceptible to infections. Early recognition of this complication can significantly reduce hospital stay, improve quality of life and reduce graft loss and mortality. In this article, we aim to develop an evidence-based management approach to a patient with urine leak using a clinical scenario.
Liver cyst infection in kidney transplant patient with autosomal dominant polycystic kidney disease: Interest of PET/CT in diagnosis and treatment
Published on: 14th December, 2018
OCLC Number/Unique Identifier: 7964794073
Liver cyst infection in patients with autosomal dominant polycystic kidney disease (ADPKD) is a rare but life-threatening complication. Diagnosis and treatment remain challenging. We report the case of a 64-year-old kidney transplant patient presenting with fever and abdominal pain. The diagnosis of liver cyst infection was made by positron emission tomography scan (PET/CT). Moreover, the course of our patient illustrates the interest of subsequent PET/CT during follow-up as our patient failed on antibiotherapy and required liver cyst drainage.
Lessons from the success and failures of peritoneal Dialysis-Related Brucella Peritonitis in the last 16 years: Case report and Literature review
Published on: 31st December, 2018
OCLC Number/Unique Identifier: 7964745961
Brucellosis is a zoonotic infection that is endemic in some Mediterranean countries, North Africa and the Middle East. Brucella is a rare cause of peritonitis in Peritoneal Dialysis (PD) population and in non-dialysis patients alike. We report here a challenging case of PD-related Brucella peritonitis in a 45-year-old Saudi male with late peritonitis that delivered some key learning throughout its course from presentation, diagnosis and treatment to catheter salvage attempts so as to circumvent PD failure. We provide an in-depth review of limited published literature on PD-related Brucella peritonitis (seven cases, and present case) and summarized the data on key clinical characteristics, management and PD technique outcome to benefit nephrologists when encountered with this rare presentation.
Relationship between Fetuin-A and vascular or valvular calcification in hemodialysis patients
Published on: 7th January, 2019
OCLC Number/Unique Identifier: 7985946207
Purpose: Deficiency of Fetuin A, as a calcification inhibitor, is assumed to be involved in vascular calcification in patients on maintenance hemodialysis (MHD). This study examined the relationship between serum Fetuin-A and vascular and valvular calcification in a cohort of MHD patients.
Methods: The study was conducted on 122 MHD patients. Serum levels of calcium, phosphorus, parathormone, and Fetuin-A were tested. Intima-media thickness (IMT) ≥0.8 mm and the presence of stenosis>50% or plaques in carotid doppler sonography were considered as vascular calcification. Calcification of cardiac valves or mitral annular calcification in two-dimensional echocardiography, were considered as cardiac valvular calcification. The presence of any or both of the two conditions was defined as cardiovascular calcification (CVC).
Results: Fetuin-A was lower than normal in 37% of 122. Totally 106 patients (87%) had CVC, who were older (61±14 vs. 38±14 years, P<0.001), more affected by diabetes (54% vs. 13%, P=0.007), had a longer dialysis vintage (median 5 vs. 2 years, P=0.006), lower levels of creatinine (8.9±2.8 vs. 11.9±3.1 mg/dL, P<0.001) and higher levels of calcium (8.7±0.7 vs. 8.4±0.5 mg/dL, P=0.026). There was no significant difference in mean Fetuin-A level between the two groups (P=0.101). In logistic regression increased age (OR=1.1, CI 95%=1.1 - 1.2) and serum calcium (OR=2.8, CI 95%=1.1- 7.6), and diabetes mellitus (OR=7.4, CI 95%=1.1 - 47.4) were risk factors.
Conclusion: This study showed that 87% of our patients had vascular and/or valvular calcification. Increased age and calcium level and diabetes were the predictors of CVC, whereas Fetuin-A was not.
Chronic kidney disease in women: a cross sectional screening in a tertiary care hospital in Varanasi
Published on: 18th January, 2019
OCLC Number/Unique Identifier: 7985982265
Background: Chronic Kidney Disease is no longer considered just a health burden today but a major health priority owing to its high treatment costs and poor outcome. World Kidney Day and International Women’s Day in 2018 coincided, thus offering an opportunity to reflect on the importance of women’s health, and specifically their kidney health. The current study aims to identify chronic kidney disease in women through a cross sectional screening in hospital based camp in Varanasi on World Kidney Day.
Methods: 138 females attending a health camp were screened for clinical parameters like serum creatinine, random blood sugar, and pregnancy complications. Demographic and anthropometric parameters were noted. Ordinal logistic regression analysis was used to find the predictors of chronic kidney disease stages.
Results: The median age of the participants was 36 years. The prevalence of chronic kidney disease was 6.4% with 1.4% of Stage 1, 2.1% of Stage 2, 1.4% of Stage 3 and 1.4% of Stage 4. Women with diabetes were nearly 4 times at a greater risk of developing higher stages of chronic kidney disease compared to women without it. With a unit increase in serum creatinine levels, women were nearly 13 times more likely to develop higher stages of chronic kidney disease.
Conclusion: Serum creatinine levels and diabetes were the significant predictors for the development of higher stages of chronic kidney disease. Early screening for kidney diseases in women could reduce the load of health care delivery system that is involved in renal replacement therapies.
Anti-Inflammatory probiotic biomarkers in Fermented foods
Published on: 24th January, 2019
OCLC Number/Unique Identifier: 7985918960
We present below a mechanistic molecular approach for development of Anti-Inflammatory biomarkers of Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses arrroaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory bathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary componenents on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.
Chronic Kidney Disease: A single day screening on World Kidney Day for five consecutive years
Published on: 12th March, 2019
OCLC Number/Unique Identifier: 8049477489
Introduction: Chronic kidney disease is a costly and burdensome public health concern. Delayed recognition and treatment of CKD may predispose patients to unfavorable future outcomes and burden the healthcare services. The early detection of disease via screening programs is widely recommended. The present study is a hospital camp-based screening for detecting patients with chronic kidney disease in Varanasi from 2014-18.
Methods: The study subjects constituted 436 apparently healthy adults (age ≥18 years) of Varanasi. Information on socio-demographic profile, personal characteristics and clinical investigations were recorded. Stepwise binary logistic regression analysis was applied to find the significant predictors of chronic kidney disease.
Results: Median age of the study subjects was 40.5 years. There were 39.7% males and 60.3% females. Chronic kidney disease was found in 23.9% subjects. Underweight, diabetes mellitus, hypertension, smoking status and higher creatinine levels came out as significant predictors of chronic kidney disease.
Conclusion: We screened apparently healthy individuals and found very high percentages of chronic kidney disease and its predictors. Henceforth, understanding the preventable and modifiable risk factors of chronic kidney disease becomes a prerequisite to intervene before risk populations reaches to irreversible stages of adverse future outcomes.
Challenges of haemodialysis: A single centre experience in South West Nigeria
Published on: 28th March, 2019
OCLC Number/Unique Identifier: 8049457944
Background: Haemodialysis is the commonest method of Renal Replacement Therapy in Nigeria. Despite an advancement in the technicality and better understanding of haemodialysis, a number of complications are known to be associated with this procedure..
Objective: We aimed to highlight our experiences and share some of the uncommon complications encountered during haemodialysis and present the outcome of our patients.
Subjects and methods: A retrospective review of 101 patients during the last two years was done. Data extracted include: sociodemographic characteristic, aetiology of kidney disease, type of vascular access, intradialytic complication and outcome of treatment.
Results: The total number of dialysis session during the period was 823. Males constituted a higher proportion (64.4%) and were found to be older than female patients 49.8 vs 42.8 years (P=0.001).
Majority (89.1%) had chronic kidney disease while chronic glomerulonephritis was the main cause of CKD as seen in about 45% of the patient.
Due to the cost implication, only 2(1.98%) were able to undergo 3 sessions of dialysis per week for up to 1 month.
Vascular access was femoral (66.3%), internal jugular vein (25.7%), while only 2% used Artero-venous-fistula and one patient had femoral vessel pseudoaneurysm from frequent cannulation.
The commonest complication was hypotension which was present in 15.8%. Twenty-eight deaths were recorded, 44(43%) were either lost to follow up or absconded while 5% were transplanted at a referral centre.
Conclusion: Challenges of renal replacement therapy is overwhelming in our country due to poor human and financial resources. Early diagnosis and adequate government support are advocated.
Anti-glomerular basement membrane disease: A case report of an uncommon presentation
Published on: 3rd April, 2019
OCLC Number/Unique Identifier: 8056273514
Anti-glomerular basement membrane (anti-GBM) disease is an uncommon autoimmune disease that classically presents as an aggressive necrotizing and crescentic glomerulonephritis (CG), with or without pulmonary hemorrhage, and typically does not relapse. The pathologic hallmark is linear staining of GBM for Immunoglobulin G (IgG) which binds to the alpha-3 chain of type IV collagen. Recent reports have noted the occurrence of anti-GBM disease with atypical clinical presentations. We describe a case of a 22-year-old female presenting an anti-GBM disease with typical histological features with a singular clinical presentation with lower limb edema, elevated serum creatinine and nephrotic range proteinuria. Renal biopsy showed signs of chronicity and direct immunofluorescence microscopy demonstrated diffuse, intense linear positivity for IgG. All serologic tests were negative, including anti-GBM antibodies. Hence, a diagnosis of atypical anti-GBM disease was made. The patient was treated initially with mycophenolate mofetil and corticosteroids. After 3 months she began to aggravate renal function so mycophenolate of mofetil was discontinued and a low dose cyclophosphamide was initiated.
Can bloodstream infection be predicted by nasal culture in hemodialysis patients?
Published on: 15th April, 2019
OCLC Number/Unique Identifier: 8163588486
The blood and drainage cultures are suggested for early diagnosis of bloodstream infection (BSI), which are time consuming and laborious. Nasal colonization of bacteria is one of the modalities, occasionally can predict BSI. We hypothesized that nasal culture, as an accessible fluid may be helpful to predict future BSI in hemodialysis patients. The present prospective study evaluated 63 patients undergoing maintenance hemodialysis at the Pars hospital dialysis center, Tehran, Iran, from November 2015 until February 2016. Nasal fluid of patients were collected from the 1–cm internal anterior part of both nostrils of patients by a sterile swab and cultured in Trypticase soy agar. All patients were followed for three months for BSI. The results of first nasal fluid sample revealed that 33.3% in first sampling and 27.0% in sampling had positive nasal fluid culture. The type of bacteria in all positive cases was Staphylococcus aureus. The rate of BSI infection in the patients with positive and negative first nasal fluid culture was 9.5% and 2.4% respectively with no significant difference. We found also no significant association between BSI positivity and nasal culture results so that positive BSI was revealed in 5.9% of patients with positive nasal fluid culture and 4.3% in those with negative nasal fluid culture with no meaningful difference. None of the baseline variables including age and gender, underlying risk factor, access, or duration of dialysis was associated with BSI positivity. In hemodialysis patients, BSI may not be predicted by nasal fluid culture positivity.
The pattern of blood pressure and renal function among children with Sickle Cell Anaemia presenting in a tertiary health institution in Nigeria
Published on: 16th April, 2019
OCLC Number/Unique Identifier: 8163611724
Background: In sickle cell anemia (SCA), compromise of the renal vasculature due to sickled red cells has been recognized.
Objectives: To assess the renal function and blood pressure pattern in children with sickle cell anaemia (SCA) presenting in a tertiary institution.
Method: A cross-sectional study of patients with sickle cell anaemia (SCA) over six months involving the use of questionnaires, general physical examination, blood pressure, investigations for haemoglobin genotype, urinalysis, serum creatinine, screening for hepatitis B and HIV.
Results: 51 children with SCA were seen. The prevalence of impaired renal function as defined by reduced eGFR <90mL/min/1.73m2 in this study was 27.5%, previous hospital admission and blood transfusion were associated with reduction in eGFR but blood pressure did not have significant correlation with the eGFR. The overall mean age at diagnosis of SCA was 4.09 ± 3.33 (years).
Conclusion: Impaired renal function is a major comorbid condition in children with SCA. In countries/locations where there is no newborn screening for sickle cell disease, diagnosis is delayed, thus detecting impaired renal function may be delayed, therefore the need for early detection and management is imperative.Introduction
Primary Cutaneous Lymphomas and Interferon Treatment
Published on: 9th January, 2017
OCLC Number/Unique Identifier: 7355942281
Primary cutaneous lymphomas (PCLs) are the second most common group of extranodal non-Hodgkin lymphomas (NHL) with an estimated annual incidence of 1/100.000. Interferons (IFNs) are used in mono or combination therapy for cutaneous lymphomas especially for cutaneous T-cell lymphomas (CTCL) for years. IFN-α is the most widely-used type for cutaneous lymphomas. IFN-α has been shown to be a highly active agent in CTCL with response rates ranging from 40% to 80%. In this review, the current information about PCLs and IFNs treatment is summarized.
Neutrophil to Lymphocyte Ratio (NLR) in Peripheral Blood: A Novel and Simple Prognostic Predictor of Non-small Cell Lung Cancer (NSCLC)
Published on: 30th March, 2017
OCLC Number/Unique Identifier: 7355938332
Lung cancer is the leading cause of cancer-related deaths worldwide, and almost accounts for 20% of these deaths, however, the cure rate is less than 10% [1]. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer [1], but fewer than 15% of individuals diagnosed with NSCLC can survive for more than 5 years, which poses a great threat to the patient’s life and health [2]. Recently, the incidence of lung cancer keeps dynamically growing, but more than 75% of patients at diagnosis has appeared local development or metastasis, missing the best period of surgery. Moreover, despite surgical treatment is the optimal choice for early-stage NSCLC patients, 30%-40% of patients with NSCLC develop tumor recurrence in a short time. Therefore, improving the prognosis of patients with lung cancer and predicting the long-term survival of patients is of particular importance [3]. At present, tumor and node metastasis (TNM) staging system, clinicopathological characteristics, visceral pleural invasion and marginal status are used to predict the disease progression and overall survival of NSCLC patients. There is no index which is stable, effective, reliable and less harmful to assess prognosis, predict recurrence risk and overall survival.
Successful management of disseminated Fusarium infection in a patient with acute myeloid leukemia
Published on: 17th September, 2018
OCLC Number/Unique Identifier: 7877981809
Background: Invasive fungal infections cause significant morbidity and mortality in patients with hematologic malignancies and in recipients of hematopoietic stem cell transplantation.
Case: We report a patient with relapsed acute myeloid leukemia who developed disseminated Fusarium infection during the neutropenic period following the salvage cycle of chemotherapy given at King Fahad specialist Hospital in Dammam, Saudi Arabia. The invasive fungal infection was successfully managed with a combination of voriconazole and liposomal amphotericin-B.
Discussion: Fusarium species can cause invasive infections that may become disseminated and life-threatening in patients with acute myeloid leukemia.
Conclusion: Combined antifungal therapy and recovery of neutrophil count are essential to control invasive Fusarium infections
Varicella zoster virus: The potentially useful virus
Published on: 5th July, 2019
OCLC Number/Unique Identifier: 8174826530
Varicella zoster virus (VZV), a double-stranded DNA virus, is a highly contagious human neurotropic virus that belongs to the alpha group of herpes viruses [1-4]. Primary VZV infection (chickenpox) occurs in childhood then the virus becomes latent in the nerve ganglia [1,5-7]. Reactivation of the virus may occur decades later and cause herpes zoster (HZ) which is manifested by a typical painful skin eruption that has characteristic dermatomal distribution [1,5]. Reactivation of VZV is usually predisposed to: old age; comorbid medical conditions such as diabetes mellitus, chronic obstructive airway disease, and end-stage renal disease; and immunosuppression due to malignancy, autoimmune disorders, immunosuppressive therapies, trauma, cytotoxic chemotherapy, hematopoietic stem cell transplantation (HSCT), and solid organ transplantation (SOT) [1,5-7].
Relation of Arachnophobia with ABO blood group system
Published on: 8th August, 2019
OCLC Number/Unique Identifier: 8212851418
In 1901, ABO system of blood groups was determined by Karl Landsteiner. It is present in different organisms like rodents, primates that includes chimpanzees, bonobos etc. The blood groups type in this system depends on some genes that are specific ABO gene. Arachnophobia is the dread of creepy crawlies and different creature like spiders. Individuals suffering from arachnophobia generally feels uneasy in any place where they accept that they could harbour arachnids or their existence for example, webs. 100 samples of blood from volunteers were used for Blood group test. The Blood groups were tested and results were recorded after the test all the used kits were discarded. The results shows that there is no clear cut difference between the arachnophobic males and non-arachnophobic male’s percentages, so no relation found in males. Similarly, in females both phobic and non-phobic ladies have no differences in their result values so, no relation was found. Whereas, in case of arachnophobic males and females comparison no relation was found. So, there is no relationship between ABO blood group system and arachnophobia and there may be a relation between non-phobia and AB+, B+ blood group in males whereas, in females only B+ blood group have relation with non-phobia.
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