Background: The development of COVID-19 having been set apart as the third presentation of an exceptionally pathogenic coronavirus into the human populace after the extreme intense SARS-COV and MERS-COV in the twenty-first century. The infection itself doesn’t make a crucial commitment to mortality, anyway “cytokine storm” created by the unreasonable invulnerable reaction activated by the virus can result in a hyperinflammatory response of lung tissues and deadly lung injury, and in this way increment death rate. In this manner, immunomodulatory medications ought to likewise be remembered for treatment of COVID-19.
Presentation of the hypothesis: the virus particles invade the respiratory mucosa firstly and infect other cells, triggering a series of immune responses and the production of cytokine storm in the body, which may be associated with the critical condition of COVID-19 patients. Once a cytokine storm is formed, the immune system may not be able to kill the virus, but it will certainly kill many normal cells in the lung, which will seriously damage the of lung function. Patients will have respiratory failure until they die of hypoxia. It is not yet clear what the death rate of Covid-19 will be, though the best estimate right now is that it is around 1 percent, 10 times more lethal than seasonal flu due to cytokines storm which trigger a violent attack by the immune system to the body, cause acute respiratory distress syndrome (ARDS) and multiple organ failure, and finally lead to death in severe cases of COVID-19 infection. Therefore, inhibiting cytokine storm can significantly reduce inflammatory injury in lung tissues.
Pyridostigmine (PDG), cholinergic anti-inflammatory pathway (CAP) is a neural mechanism that modulates inflammation through the release of acetylcholine (ACh), resulting in decreased synthesis of inflammatory cytokines such as TNF-α and IL-1. This finding emphasis, the nervous and immune systems work collaboratively during infection and inflammation.
Implications of the hypothesis: Administrations of Pyridostigmine (PDG) as cholinergic agonist inhibits the inflammatory response and lower the mortality of COVID-19 patients. Likewise, activation of the CAP during systemic inflammation down-regulates the production and release of inflammatory cytokines.
The infectivity and pathogenesis: SARS-CoV-2, the causative agent of Covid-19, involves Angiotensin-converting enzyme 2 (ACE2) receptors on type II alveolar type 2 (AT2) cells in lungs. Apart from, the upper and lower respiratory tracts, the disease affects the gastrointestinal system prominently, as evidenced by the significant GI symptoms, early in the course of the disease. In addition, the virus infects ACE2-bearing cells in other organs including the heart and blood vessels, brain, and kidneys.
Clinical features and morbidity: The clinical spectrum of COVID-19 varies from asymptomatic or pauci-symptomatic presentation to moderate to severe states characterized by respiratory failure necessitating mechanical ventilation and ICU support and those manifesting critical clinical condition with complications like sepsis, septic shock, and multiple organ dysfunction failure. The CT chest is an important tool for early identification of COVID-19 pneumonia as well as for prognostic purposes.
The recovery and residual damage: The recovery and other outcomes vary depending on age and other aspects including sex, comorbidities, and genetic factors. The outlook for older adults, who account for a disproportionate share of critical disease, is unfavorable, and most of those who survive are unlikely to return to their previous level of functioning. The disease affects their long-term health and quality of life as well as brings in propensity for truncated post-disease survival.
COVID-19 aftermath and follow up: The patients discharged from hospital following severe COVID-19, continue to suffer with lingering impact of the disease as well as that of the emergency treatments that saved their life. The post-infection reduced exercise tolerance and other subtle factors, like post viral fatigue syndrome, post-traumatic stress disorder, impaired concentration, delirium, and disturbed sleep-wake cycle often underly the functional impairment. In fact, there is need of step-down care and later a multidisciplinary support involving regular clinical assessment, respiratory review, physiotherapy, nutritional advice, and psychiatric support.
Conclusion: The life after COVID-19: After recovery from the disease, the virus SARS-CoV-2, may persist for uncertain period. In addition, the chance of reinfection cannot be ruled out. The vitamin D supplementation may be helpful. In general, the quality of life (QOL) in ICU survivors improves but remains lower than general population levels, but most of the patients adapt well to their level of self-sufficiency and QOL. Also, the debility due to co-morbidities may further compromise the activity of daily living and QOL issues. The Age and severity of illness appear to be the major predictors of post-discharge physical functioning.
MMK Mbula*, HNT Situakibanza, GL Mananga, B Longo Mbenza, JRR Makulo, MM Longokolo, MN Mandina, NN Mayasi, MM Mbula, B Bepouka, GL Mvumbi, BT Buasa, EN Amaela, DN Tshilumba, O Odio and A Nkodila
Introduction: HIV infection leads to metabolic disorders. The objective of this work was to study the lipid profile of HIV + patients followed at the University Teaching Hospital of Kinshasa (UTHK).
Methods: This study analyzes the lipid profile of HIV + patients, aged at least 18 years, followed at the UTHK from January 1, 2008 to December 31, 2014. The medians of different types of lipids, the frequency of lipid disorders, the general clinical characteristics of patients and factors associated with dyslipidaemia were studied. Haemoglobin (Hb), White Blood Cells (WBC), Leukocyte Formula (LF), Blood Sugar, Urea, Creatinine, Transaminases, Uric Acid, CD4s+ count were analyzed.
Results: The lipid balance was performed in 38.8% of patients; 38.1% of them had dyslipidaemia. Total hypercholesterolaemia (28.6%), elevated LDL-C (19%), hypertriglyceridemia (23.8%) and HDL hypocholesterolaemia (42.9%) were observed. The medians of TG (128 mg / dL), HDL-C (51 mg/dL) and LDL-C (78 mg/dL) were high. Risk factors associated with dyslipidaemia were represented by WHO stage 4, tuberculosis (TB) and hyperglycaemia. The highest levels of LDL-C and TG and the lowest HDL-C were seen when CD4s+ were below 200 elements/µL.
Conclusion: The HIV/AIDS dyslipidaemia characterized in this study by HDL-C hypocholesterolaemia, hypertriglyceridemia and total and LDL hypercholesterolemia can be considered as an indicator of the progression of HIV infection.
Introduction: SARS-CoV-2 life cycle: The disease which reportedly began in Chinese city Wuhan in November-December 2019 manifesting as severe respiratory illness, soon spread to various parts of the world, and was named COVID-19, and declared a pandemic by WHO. The life cycle of SARS-CoV-2 begins with membrane fusion mediated by Spike (S) protein binding to the ACE2 receptors. Following viral entry and release of genome into the host cell cytoplasm there occurs replication and transcription to generate viral structural and non-structural proteins. Finally, VLPs are produced and the mature virions are released from the host cell.
Immunogenicity of the spike protein: The S protein is considered the main antigenic component among structural proteins of SARS-CoV-2 and responsible for inducing the host immune response. The neutralising antibodies (nAbs) targeting the S protein are produced and may confer a protective immunity against the viral infection. Further, the role of the S protein in infectivity also makes it an important tool for diagnostic antigen-based testing and vaccine development. The S-specific antibodies, memory B and circulating TFH cells are consistently elicited following SARS-CoV-2 infection, and COVID-19 vaccine shots in clinical trials.
The emerging SARS-CoV-2 variants: The early genomic variations in SARS-CoV-2 have gone almost unnoticed having lacked an impact on disease transmission or its clinical course. Some of the recently discovered mutations, however, have impact on transmissibility, infectivity, or immune response. One such mutation is the D614G variant, which has increased in prevalence to currently become the dominant variant world-over. Another, relatively new variant, named VUI-202012/01 or B.1.1.7 has acquired 17 genomic alterations and carries the risk of enhanced infectivity. Further, its potential impact on vaccine efficacy is a worrisome issue.
Conclusion: THE UNMET CHALLENGES: COVID-19 as a disease and SARS-CoV-2 as its causative organism, continue to remain an enigma. While we continue to explore the agent factors, disease transmission dynamics, pathogenesis and clinical spectrum of the disease, and therapeutic modalities, the grievous nature of the disease has led to emergency authorizations for COVID-19 vaccines in various countries. Further, the virus may continue to persist and afflict for years to come, as future course of the disease is linked to certain unknown factors like effects of seasonality on virus transmission and unpredictable nature of immune response to the disease.
“Pharmacodynamics of cannabinoids “(i.e. a set of biological effects elicited in the living organism by interaction with its biochemical and biophysical functions up to the cellular level) is studied for a long time during both, physiological and pathological conditions. Cannabinoids received their names according to their natural occurrence as constituents of Cannabis sativa L. (marijuana).
Juvenile xanthogranuloma (JXG) is a rare form of non-Langherans cell histiocytosis (non-LCH) observed almost exclusively in infants and young children. It is rarely systemic, involving extracutaneous sites, such as the liver, lungs, spleen, kidney, pancreas, bone or central nervous system. Systemic JXG may be associated with significant complications requiring aggressive medical or surgery care; especially, central nervous system lesions are difficult to treat and reported to be possibly fatal. Clinical presentation of JXG of central nervous system is not specific and is related to the involved site while magnetic resonance imaging examination remains the first choice for localizing the lesions. If no other system is involved, surgical excision could be sufficient.
Background: Interleukin-6 (IL-6) promotes antibody production. The objective of this study was to investigate whether IL-6 C-572G single nucleotide polymorphisms (SNP) and clinical factors are associated with positive platelet antibody test.
Materials and methods: Thirty platelet recipients with platelet antibodies (responders) and 20 platelet recipients without platelet antibodies (non-responders) were randomly selected. The -572 C>G (rs 1800796) SNPs in the promoter region of IL-6 gene were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Solid phase red cell adherence assay (SPRCA) was used for platelet antibody detection.
Results: Age, sex, percentage patients with benign diseases, and percentage of patients with homozygotes for the C allele at position -572 of the IL-6 gene were similar between responders and non-responders. Although the amounts of platelets pheresis transfused to patients with hematologic diseases were higher than those of non-hematologic diseases (47.2 ± 54.2 vs. 17.4 ± 13.8 units, p = 0.019), detection rate of platelet antibodies was lower in patients with hematologic diseases than that in patients with non-hematologic diseases (42.3% vs. 79.2%, p = 0.01).
Conclusion: There was no association between IL-6 C-572G gene polymorphism and positive reactivity in solid phase platelet antibody detection method in platelet recipients.
Nearly all energy production in living organisms is by oxidation reactions (fires are large oxidative embers)
Oxidation reactions produce, through complex intermediate steps, small energy packages that are more easily stored than a sudden combustion oxidation. The slow and controlled production of energy in a nuclear power plant allows its use, a massive explosion produces the result that we know ... It’s the same thing in our bodies. These reactions are never 100% efficient, not all the energy produced is used as bio fuel. Indeed, during the intermediate stages, they induce a deterioration of cells and tissues by consuming about 10% of this energy. They cause significant “wear and tear” when there is no longer any compensation for these parasitic oxidations. The latter can be excessively used in pathological situations inducing inflammatory reactions, or simply during metabolic overproduction, or even simple intense and prolonged efforts.
Burns injuries induce a state of immunodepression that predisposes to a bacterial infectious complication that leads to several comorbid diseases and high mortality rate. Previous studies about anti-inflammatory, antimicrobial and antioxidant properties of Aloe vera (L.) Burm., Calendula officinalis L.and Matricaria recutita L. are acknowledge by antimicrobial effects.
Previous studies about anti-inflammatory, antimicrobial and antioxidant properties of Aloe vera (L.) Burm., Calendula officinalis L. and Matricaria recutita L. are knowledge by antimicrobial effects. Bacterial cellulose membrane (nature BCM) is a potential carrier as a drug delivery system in the wound and burn treatment. The present study aimed to evaluate the antibacterial activity of extracts of A. vera, C. officinalis, and M. recutita incorporated in BCM against bacterial strains commonly present in wound and burns. The agar-dilution susceptibility testing was used to determine the minimum inhibitory concentration (MIC) for S. aureus, E. coli, and P. aeruginosa. The standardized extracts of A. vera, M. recutita, and C. officinalis were, respectively, used at 3.25% of total polysaccharides, 1% of apigenin 7-O-glucoside and 0.084% of total flavonoids expressed in quercetin. The BCM incorporated with A. vera extract was efficient to prevent the growth of P. aeruginosa and S. aureus. BCM loaded with C. officinalis inhibited the growth of S. aureus. The BCM loaded with A. vera and C. officinalis extract showed better antibacterial activities against P. aeruginosa and S. aureus and, consequently, properties to prevent infectious disease in the wound or burn caused by these bacteria.
In this manuscript it has been described a novel synthesis of mercury doped hydroxyapatite (Hap) and its application on human liver carcinoma cell line (Hep G2) and human lung fibroblast carcinoma cell line (MRC 5). Nano-sized hydroxyapatite doped with Hg2+ was synthesized by a solution based chemical method along with mercury ion. The surface of nanoparticle of mercury doped hydroxyapatite (MHAp) was functionalized by using phosphonomethyl iminodiacetic acid (PMIDA) for making it stable as dispersed phase with negative zeta potential. Surface functionalization was confirmed by FTIR measurements. Crystalline nature, morphology and surface topology were studied by powder XRD, FESEM and AFM measurements. Particle size of the well dispersed sample was obtained by HRTEM image. The studies on cell viability of Hep G2 and MRC 5 cell in presence of mercury doped HAp nanoparticle (MHAp) were determined through WST assay. It was observed that nanocomposite exhibited a site specific action towards MRC 5 cell lines along with reduction of toxicity toward normal cells.
Several experimental studies performed since 1975, using smooth muscles richly innervated by sympathetic nerves to exclude the autonomic influence of adjusting reflex (rodent vas deferens), showed that L-type voltage-activated Ca2++ channels (VACC) blockers completely inhibited neurogenic contractions induced by electrical field stimulation (EFS) in high concentrations (>10-6 M), but paradoxically increased these EFS-contractions in low concentrations (<10-6 M), suggesting that other mechanisms than only autonomic adjusting reflex are involved in these paradoxical effects. In 2013, we showed that these paradoxical effects of L-type VACC blockers, named by us “calcium paradox” phenomenon, were potentiated by drugs which increase cytosolic cAMP concentration ([cAMP] c-enhancers), such as rolipram, IBMX and forskolin, indicating that this sympathetic hyperactivity drug-induced is due to interaction of the Ca2+/cAMP intracellular signaling pathways (Ca2+/cAMP interaction). Then, the pharmacological manipulation of this interaction produced by combination of the L-type VACC blockers used in the antihypertensive therapy, and [cAMP] c-enhancers used in the antidepressive therapy, could represent a potential cardiovascular risk for hypertensive patients due to sympathetic hyperactivity. Then, we discussed the role of Ca2+/cAMP interaction for antihypertensive pharmacotherapy.
Type 2 diabetes is a common disease in these days and day by day it is arising. The main focus of the study was to investigate association of packed cell volume (PCV), Mean Corpuscular Volume (MPV), Mean Corpuscular Hemoglobin Concentration (MCHC), Red Cell Distribution Width (RDW) with glycemic marker HbA1c. So that PCV, MPV, MCHC, RDW could be used as a predictor of glucoregulation in type 2 diabetes instead of HbA1c value. This study included 87 DMT2 patients, which divided into two groups, A (n=41, presence in diabetics≤6.5-6.9%) and B (n=46, target in diabetes≥7.0%), according to HbA1c values. Spearsman correlation co-efficients were calculated to evaluate the relationship between RBC count, MCHC, RDW with random blood sugar (RBS) and PCV, MCV, MCHC with HbA1c value. Binominal logistic regression analysis was performed to estimate the relationship between glycemic control, as dichotomous outcome of MCHC, RDW, PCV, and MCV as the main prognosticator. MCHC and RDW were significantly higher in the group B compared to the group A. RDW and MCHC may be applied as the auxiliary indicators of deterioration of glucoregulation.
In this review After Observing biomedical literature (starting from some heart disease) results that some pathological phenomena are deeply involved in some metabolic endocrine condition: Kinetics and gradients in metabolism, catabolism, time related, toxic like effect, electrical cell membrane status, smooth vascular muscle cell hyper-reactivity, platelet iperactivations, central autonomic control after acute stroke, great electrolytes unbalances et other factors as pro-hypertrophic signaling and oxidative stress. Observing actual current therapy in some metabolic endocrine therapy often is used association of drugs (in example in type II diabetes). In Many other pathologies efficacy drug therapy exist, and often only 1 pharmacological molecule resolve the pathological condition. But in many disease even associating 2-3-4 drugs the % of cure not increase (efficacy, effectiveness). It mean that this drugs strategies are not the really best? Or it mean a low active level? Why for this pathological condition this association drugs in currently use not do the right works as really needed? There is the need for new really efficacy drugs strategy that show a profile of efficacy as requested in order to resolve the pathological condition? Or to be added to the actual therapy? The actual pharmacological strategies in some metabolic endocrine disorder is really the best? Or other strategies can be introduced?
Previous clinical, observation and epidemiologic studies have demonstrated strong association between serum uric acid (SUA) and cardiovascular disease (hypertension, heart failure, and asymptomatic atherosclerosis), metabolic states (abdominal obesity, diabetes mellitus, metabolic syndrome, insulin resistance) and kidney disease. There is a large body of evidence regarding the role of SUA as predictor of CV events and CV mortality in general population and individuals with established CV disease and metabolic diseases. However, SUA may exhibit protective effects on endothelium and vasculature as well as attenuate endogenous repair system through mobbing and differentiation of cell precursors. Although SUA lowering drugs are widely used in patients with symptomatic hyperuricemia and gout beyond their etiologies, there is no agreement of SUA below target level 6.0 mg/dL in asymptomatic individuals with kidney injury and CV disease and data of ones are sufficiently limited. The short communication is depicted on the controversial role of SUA as primary cell toxicity agent and secondary cell protector against hypoxia, ischemia and apoptosis
Jiawei Zhao, Zhihong Yang, Min He, Qinghua Wang and Renming Hu*
Published on: 19th June, 2018
Although exercise has been proposed to be beneficial to type 2 diabetes, its effects on β-cell function and mass remain unclear. In the present study, the effects of long-term swimming training on the function and mass of β-cells in diabetic OLETF rats were examined. At 44 weeks of age after developing diabetes, the OLETF rats were divided into two groups: a control group and an exercise group. The exercise group had a daily swimming for 12 weeks. While not found with the control rats, in the obese OLETF rats, the exercise reduced the weight gain which was associated with improved glucose tolerance and elevated circulating insulin levels as determined by the oral glucose tolerance test and insulin ELISA. The exercise improved plasma total cholesterol and triglyceride levels, and also significantly increased the islet β-cell mass and pancreatic insulin content associated with decreased β-cell apoptosis and elevated activation of the serine/threonine kinase, Akt. The present studies suggest that exercise improves diabetes symptoms via enhancement of the β-cell mass and function through decreasing glucolipotoxicity and reducing β-cell apoptosis by activating Akt in obese OLETF rats.
Hypertension is one of the most common chronic diseases of human, affecting more than one billion people worldwide. When it becomes chronic, hypertension leaves behind cardiac hypertrophy, heart failure, stroke, and kidney disease, resulting in substantial morbidity and mortality. Treatments that effectively reduce blood pressure can prevent these complications. Abnormalities in the production of urine by the kidneys have been implicated in increased vascular resistance, leading to high blood pressure and increased cardiac mass. By matching urinary excretion of salt and water with dietary intake, balance is usually attained, thereby maintaining a constant extracellular fluid volume and blood pressure. Based on the capacity for the kidney to excrete sodium, this blood pressure-altering mechanism should have sufficient advantage to limit intravascular volume and consequently lower blood pressure in response to a range of stimuli from elevated heart rate to increase peripheral vascular resistance. A major determinant of the level of intra- and extra- renal blood pressure is therefore sodium handling, and it is controlled by complex physiological mechanism by hormones, inflammatory mediators, and the sympathetic nervous system. Homoeostasis and favourable influence sodium balance are a basic mechanism of efficacy for diuretics and dietary sodium restriction in hypertension. Renin Angiotensin System (RAS) inhibitors, vasodilators, and β-blockers work to facilitate pressure-natriuresis. Also, WNK signaling pathways, soluble inflammatory mediators, and pathways regulating extra-renal sodium disposition may be the focus towards elimination of sodium and reducing blood pressure in hypertension.
The phenotypic manifestation of congenital adrenal hyperplasia (CAH) is variable, and this largely depends on the extent of 21-Hydroxylase enzyme deficiency. In non- classic CAH (NCCAH), the clinical features predominantly reflect the androgen excess rather than adrenal insufficiency. In boys, the condition may not present until much later in childhood, where the diagnosis is made following presentation with precocious puberty, features of aldosterone insufficiency, or this condition may be detected during fertility workup Imaging is generally not used in the evaluation of CAH, but may be helpful for the diagnosis, management, and follow-up of these patients. CAH can result in adrenal enlargement in both classic and non-classic forms of adrenal hyperplasia. The so-called adrenal rest tissue may be seen at several sites throughout the body, including the celiac plexus region, broad ligaments, normal ovaries, and testes. Sustained elevation of adrenocorticotropic hormone (ACTH) in patients with CAH has been postulated to cause adrenal rest cells to grow and become functionally active. The discovery of bilateral adrenal enlargement during radiologic evaluation for unrelated disease processes might serve as a mode of presentation for clinically not apparent or non- classical congenital adrenal hyperplasia (NCCAH).
Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer and a highly curable malignancy [1]. However, despite its excellent prognosis, cervical lymph node metastases (CLNMs) are present in a significant percentage of patients with papillary thyroid cancer (PTC) (upto 50% - 60%) [2].
Linear IgA bullous dermatosis (LABD) is a rare, chronic, autoimmune bullous dermatosis affecting young children and adults. The exact pathogenesis of this disease is still unknown, although both humoral and cellular immune response are involved. Clinically, it may show heterogeneous skin manifestations. However, it is characterized histologically by linear immunoglobulin A (IgA) deposits over the basal membrane, causing subepidermal blisters. Studies on LABD are relatively sparse and most of the publications are small series or single case reports. Several treatments are reported in literature, however, they should be used with care due to the risk of side effects. We report a case of linear IgA dermatosis with generalized lesions in a 7 year old child, with good outcome under dermocorticoids and antibiotics.
Actinic keratosis (AK) are scaly lesions caused by chronic ultraviolet-induced damage to the epidermis which are a proxy for excessive sun-exposure [1] that may evolve into squamous cell carcinoma [2-7]. Therefore, there is a need or continuous surveillance of such patients along with adapted information for an effective photo-protection, practical couselling on photoprotection towards the defined population, i.e. elderly with actinic keratosis. Thus, patient observance and adhesion to the dermatologist recommendations become a real public health issue. In this context, we aimed to evaluate through a non-interventional, real-life observational study, the impact of photoprotection counseling by the dermatologist on patients attitude towards sun exposure
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