Acute Systemic Diseases Research Articles

Thallium reabsorption via NKCC2 causes severe acute kidney injury with outer medulla-specific calcium crystal casts in rats.

Thallium (Tl) is one of the most toxic heavy metals, associated with accidental poisoning and homicide. It causes acute and chronic systemic diseases, including gastrointestinal and cardiovascular diseases and kidney failure. However, few studies have investigated the mechanism by which Tl induces acute kidney injury (AKI). This study investigated the toxic effects of Tl on the histology and function of rat kidneys using biochemical and histopathological assays after intraperitoneal thallium sulfate administration (30mg/kg). Five days post-administration, rats exhibited severely compromised kidney function. Low-vacuum scanning electron microscopy revealed excessive calcium (Ca) deposition in the outer medulla of Tl-loaded rats, particularly in the medullary thick ascending limb (mTAL) of the loop of Henle. Tl accumulated in the mTAL, accompanied by mitochondrial dysfunction in this segment. Tl-loaded rats showed reduced expression of kidney transporters and channels responsible for Ca2+ reabsorption in the mTAL. Pre-administration of the Na-K-Cl cotransporter 2 (NKCC2) inhibitor furosemide alleviated Tl accumulation and mitochondrial abnormalities in the mTAL. These findings suggest that Tl nephrotoxicity is associated with preferential Tl reabsorption in the mTAL via NKCC2, leading to mTAL mitochondrial dysfunction and disrupted Ca2+ reabsorption, culminating in mTAL-predominant Ca crystal deposition and AKI. These findings on the mechanism of Tl nephrotoxicity may contribute to the development of novel therapeutic approaches to counter Tl poisoning. Moreover, the observation of characteristic Ca crystal deposition in the outer medulla provides new insights into diagnostic challenges in Tl intoxication.

Psittacosis Pneumonia: Diagnosis, Treatment and Interhuman Transmission.

Psittacosis pneumonia is a zoonosis caused by Chlamydia psittacosis infection, mainly resulting from contact with aerosols of birds or poultry's urine, feces, and excrement. The clinical manifestations range from general symptoms of infection to severe acute respiratory syndrome and systemic diseases, currently diagnosed using metagenomic next-generation sequencing (mNGS) to improve diagnostic accuracy. To date, most reports have only discussed human exposure to poultry disease. However, the latest studies have shown that human-to-human transmission of Chlamydia psittaci occurs not only between infected patients and their close contacts but also between secondary contacts. After looking back on relevant literature at home and abroad in the past ten years, this paper reviews the diagnosis, diagnosis and treatment, and progress in epidemiological research of Psittacosis pneumonia.

STING modulates necrotic cell death in CD4 T cells via activation of PARP-1/PAR following acute systemic inflammation

Regulated cell death profoundly affects on the progress of inflammatory and immune responses in various acute inflammatory diseases, as seen in sepsis and trauma. However, the mechanisms underlying CD4 T cells death have not yet been fully addressed. We demonstrated that interferon genes (STING) promoted excessive Poly (ADP-ribose) polymerase 1 (PARP-1) activity stimulated by endotoxin, which in turn induced apoptosis-inducing factor (AIF)-independent but PARP-1 dependent programmed cell death. Elevated PARP-1 activity triggered a cascade of molecular events, including PAR polymer release from the nucleus and the nicotinamide adenine dinucleotide (NAD+) and ATP depletion. Interestingly, translocation of AIF, a biochemical signature for PARP-1-dependent parthanatos, was not observed in the present study, suggesting a non-canonical mechanism of CD4 T cells parthanatos. In this study, we also identify a STING-mediated mechanism of necrotic cell death in CD4 T cells in septic animals. Furthermore, we revealed wider effects of STING on the mortality in mice when PARP-1 gene inhibited. These findings reveal that STING signaling and targeting PARP-1/PAR pathway in CD4 T cells may present a new therapeutic strategy for the treatment of acute systemic inflammatory diseases.

Study of hypoalbuminemia in paediatric intensive care unit admitted children

Background: Albumin has several important properties in both health and disease. Hypoalbuminemia has been considered as an indicator of disease severity and mortality in adult patients, but its role in pediatric patients is not well established. Study aimed to understand importance of hypoalbuminemia in critical illness in paediatric patients.Methods: This was a cross-sectional study conducted amongst children aged 2 months to 18 years admitted at PICU of a tertiary care hospital over a period of 6 months. Study protocol was approved by institutional ethical committee.Results: Amongst the total studied cases (110), 59 cases of the total contributed to hypoalbuminemia. According to primary system affected, post COVID MISC, acute infectious diseases, systemic inflammatory disease and sepsis are some of the common conditions associated with higher incidence of hypoalbuminemia. Statistically significant difference was found in this group of population. Amongst the hypo-albuminemic group 59 (53.64%), in mild category there were 42 (38.18%) patients and in severe category there were 17 patients (15.46%).Conclusions: Hypoalbuminemia is common in patients admitted to the PICU. Post COVID MISC, acute infectious diseases, sepsis and systemic inflammatory diseases are most common conditions associated with it. Hypo-albuminemiais an important indicator of mortality in PICU and serum albumin is a good and reliable indicator for detecting mortality.

7,7″-Dimethoxyagastisflavone Inhibits Proinflammatory Cytokine Release and Inflammatory Cell Recruitment through Modulating ERα Signaling.

Acute systemic inflammatory diseases, including sepsis, usually result in cytokine disorder and multiple-organ failure. 7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus x media var. Hicksii, has previously been evaluated for its antiproliferative and antineoplastic effects in cancer cells. In this study, the effects of DMGF on the cytokine production and cell migration of inflammatory macrophages were investigated. The inhibition of cytokine and chemokine production by DMGF in LPS-treated macrophages was analyzed by a multiplex cytokine assay. Then, the integrin molecules used for cell adhesion and regulators of actin polymerization were observed by RT-PCR and recorded using confocal imaging. The DMGF interaction with estrogen receptor α (ERα) was modeled structurally by molecular docking and validated by an ERα reporter assay. DMGF inhibited TNF-α, IL-1β, and IL-6 production in LPS-induced macrophages. DMGF also inhibited inflammatory macrophage migration by downregulating the gene and protein expression of adhesion molecules (LFA-1 and VLA4) and regulators of actin assembly (Cdc42-Rac1 pathway). DMGF might interact with the ligand-binding domain of ERα and downregulate its transcriptional activity. These results indicated that DMGF effectively inhibited the production of proinflammatory cytokines and the recruitment of inflammatory cells through downregulating ERα signaling.

The role of cardiovascular calcifications in COVID-19

Abstract Background Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. Purpose The principal aim was to evaluate the association of coronary artery calcium (CAC) and total thoracic calcium on in-hospital mortality in COVID-19 patients. Then, to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by CAC. Methods 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included in the SCORE COVID-19 registry (calcium score for COVID-19 Risk Evaluation). At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. A specific sub analysis on CAC was performed stratifying the patients in three groups: (a) “clinical CAD” (prior revascularization history), (b) “subclinical CAD” (CAC >0), (c) “No CAD” (CAC=0). In-hospital mortality was the primary endpoint, while a composite of myocardial infarction and cerebrovascular accident (MI/CVA) was the secondary one. Results Non-survivors compared to survivors had higher coronary artery [(487.7±565.3 vs 207.7±406.8, p<0.001)], aortic valve [(322.4±390.9 vs 98.2±250.7 mm2, p<0.001)] and thoracic aorta [(3786.7±4225.5 vs 1487.6±2973.1 mm2, p<0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046 - 1.637, p=0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200 - 3.251, p=0.007) resulted to be independent predictors of in-hospital mortality. In the sub - analysis increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p<0.001) and MI/CVA events (2.3% vs. 3.8% vs. 11.9%, p<0.001) were observed from the No CAD to the clinical CAD groups. Among patients with subclinical CAD, increasing CAC burden was associated with higher rates of in-hospital mortality (20.5% vs. 27.9% vs. 38.7% for patients with CAC score thresholds ≤100, 101–400 and >400, respectively, p<0.001) Conclusion Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk. Cardiovascular calcifications may represent a bystander of an impaired vascular reserve, both microvascular and endothelial, but also a sign of vascular senescence. Therefore, it can be considered an index of biological frailty, likely more accurate than age and other risk factors. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Masticatory Ability and Oral Health Related Quality of Life in Partially Edentulous Patients Involving Posterior Teeth after Rehabilitation with Tooth-Supported Fixed Dental Prosthesis

Background: Loss of teeth affects the masticatory ability and overall health of the patient especially posterior teeth as they contribute more to mastication as compared to anteriors. Loss of teeth can lead to undesirable consequences and early rehabilitation with any type of prosthesis can lead to desirable changes and thus missing teeth should be replaced as soon as possible.
 Aims and Objectives: To determine the change in masticatory ability and quality of life (QoL) after replacement of missing posterior teeth by fixed dental prosthesis.
 Methodology: Maximum bite force was recorded before and after treatment. Also a self-perceived questionnaire was filled by the patient to assess the change in QoL. Patients with missing posterior teeth were included. Patients with acute infections or systemic diseases were excluded.
 Results: Significant change (p=0.0001) in both masticatory ability and QoL of the patient was seen. The co-relation of both was clinically significant while statistically non-significant (p=0.77). Results were significant for both the studied parameters but co-relation between them was no significant. It is because of the patients perceived satisfaction of the overall treatment.
 Conclusion: Rehabilitation of posterior teeth improves mastication and also overall oral health related QoL.

The Link between SARS-CoV-2 Infection, Inflammation and Hypercoagulability-Impact of Hemorheologic Alterations on Cardiovascular Mortality.

The link between severe forms of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and cardiovascular diseases has been well documented by various studies that indicated a higher risk of cardiovascular complications in COVID-19 patients, in parallel with a higher risk of mortality in COVID-19 patients with underlying cardiovascular diseases. It seems that inflammation, which is a major pathophysiological substrate for both acute myocardial infarction and severe forms of COVID-19, may play a pivotal role in the interrelation between these two critical conditions, and hypercoagulability associated with SARS-CoV-2 infection could be responsible for acute cardiovascular complications. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) proved to be independent predictors for prognosis in acute coronary syndromes and systemic inflammatory diseases; therefore, they may be used as independent prognostic markers of disease severity in COVID-19 infection. The aim of this review is to present the most recent advances in understanding the complex link between SARS-CoV-2 infection, inflammation and alteration of blood coagulability and hemorheology, leading to major cardiovascular events.

Abstract 2953: Humanized IL6/hIL6R mouse model supports the evaluation of therapeutic drug candidates targeting to human IL6 and IL6 receptor

Abstract Interleukin 6 (IL-6) gene encodes a cytokine that functions in inflammation and the maturation of B cells and is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response Evidence of recent research shows blockade of IL-6 and IL-6 receptor interaction can offer a broader therapeutic strategy for various diseases included in acute systemic and chronic inflammatory diseases. The development of humanized mouse model can greatly support preclinical evaluation of human IL6 and IL6 receptor therapeutic drugs. To evaluate the efficacy of IL-6 and IL-6R therapeutic drug candidates, Biocytogen has generated a double humanized B-hIL6/hIL6R mouse model. In this model, the mouse IL6 gene that encodes the full length was replaced with the corresponding human sequences and the CDS of human IL6R gene was inserted into the IL6RA gene in B-hIL6/hIL6R mice. Human IL6 or IL6R protein expression was detected in homozygous B-hIL6/hIL6R mice by species-specific IL6 ELISA kit, also evaluated by flow cytometry. In efficacy study of anti-human IL6 antibodies in B-hIL6/hIL6R mice with collagen induced arthritis (CIA) , the IL6 antibody treatment reversed the disease progression by decreasing the total clinical score compared to the control group. The efficacy suggests that the B-hIL6/hIL6R mouse model is an effective tool for in vivo efficacy study in the development of IL6 and IL6R antibodies which provide a promising potential in future human clinical trials. Citation Format: Lei Zhao, Yang Mao, Linlin Wang, Yichao Chen, Leila Kokabee, Qingcong Lin. Humanized IL6/hIL6R mouse model supports the evaluation of therapeutic drug candidates targeting to human IL6 and IL6 receptor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2953.

Electrolyte and acid-base imbalance in severe COVID-19.

Acute systemic diseases, such as severe infections, can lead to electrolyte and acid-base alterations. To study the presence of electrolyte imbalance in severe COVID-19, we investigated the frequency and consequences of changes in electrolyte and acid-base patterns over time. We performed a retrospective cohort study including 406 patients with severe COVID-19. Levels of electrolytes, base excess, pH, serum osmolality, and hematocrit, the first 2 weeks of hospitalization, were collected daily from the laboratory database and clinical data from patients’ medical records. We found that hyponatremia was present in 57% of the patients at admission and 2% in hypernatremia. However, within 2 weeks of hospitalization 42% of the patients developed hypernatremia, more frequently in critically ill patients. Lower levels of sodium and potassium during admission were associated with the need for mechanical ventilation. Decreased pH at admission was associated with both death and the need for mechanical ventilation. Hypernatremia in the ICU was combined with rising base excess and a higher pH. In the group without intensive care, potassium levels were significantly lower in the patients with severe hypernatremia. Presence of hypernatremia during the first 2 weeks of hospitalization was associated with 3.942 (95% CI 2.269–6.851) times higher odds of death. In summary, hypernatremia was common and associated with longer hospital stay and a higher risk of death, suggesting that the dynamics of sodium are an important indicator of severity in COVID-19.

Coronary and total thoracic calcium scores predict mortality and provides pathophysiologic insights in COVID-19 patients

BackgroundCoronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. ObjectivesThe aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. Methods1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients’ outcomes. ResultsNon-survivors compared to survivors had higher coronary artery [Agatston (467.76 ​± ​570.92 vs 206.80 ​± ​424.13 ​mm2, p ​< ​0.001); Volume (487.79 ​± ​565.34 vs 207.77 ​± ​406.81, p ​< ​0.001)], aortic valve [Volume (322.45 ​± ​390.90 vs 98.27 ​± ​250.74 mm2, p ​< ​0.001; Agatston 337.38 ​± ​414.97 vs 111.70 ​± ​282.15, p ​< ​0.001)] and thoracic aorta [Volume (3786.71 ​± ​4225.57 vs 1487.63 ​± ​2973.19 mm2, p ​< ​0.001); Agatston (4688.82 ​± ​5363.72 vs 1834.90 ​± ​3761.25, p ​< ​0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046–1.637, p ​= ​0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200–3.251, p ​= ​0.007) resulted to be independent predictors of in-hospital mortality. ConclusionCoronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk.

Should Scrotal Color Doppler Ultrasound Be Routinely Indicated in Fertility Evaluation of Non-Azoospermic Men?

Objective: Scrotal ultrasound is not a routine investigation in the clinical approach to male infertility analysis. This study aims to identify the role of testicular Doppler ultrasound in male infertility assessment and its relation to semen parameters in non-azoospermic men. Methods: Cross-sectional descriptive analysis of 558 men from infertile couples were examined at the Hue Center for Reproductive Endocrinology and Infertility, Hue University Hospital from June 2016 to May 2018. Some cohort characteristics, semen analysis and testicular Doppler ultrasound were analyzed. Men with acute systemic diseases, acute urinary tract infection, hepatic dysfunction, malignant diseases, retrograde ejaculation, cryptorchidism or azoospermia were excluded. Results: The mean volumes of the right and left testicles were 8.87 and 8.77 ml, respectively. The total volume of the 2 sides was 17.63 ± 4.34 ml (95% confidence interval 17.27-18.00 ml). The mean right resistive index (RI) was 0.61 ± 0.23, and the mean left RI was 0.59 ± 0.01. The rate of normal semen quality was 23.2% in group with varicocele and 30.6% in group with non-varicocele. The ultrasound results from the normal semen group were much different from those of the abnormal semen group regarding testicular volume: mean right testis volume: 9.67 ± 1.88 vs. 8.75 ± 2.34 ml, p = 0.0096; mean left testis volume: 9.54 ± 1.78 vs. 8.51 ± 2.44 ml, p = 0.0047; mean total volume of 2 sides: 19.21 ± 3.60 vs. 17.26 ± 4.59 ml, p = 0.005 (varicocele group); mean right testis volume: 9.21 ± 2.21 vs. 8.63 ± 2.21 ml, p = 0.029 (non-varicocele group). The other indexes of color Doppler ultrasound (peak systolic velocity, end diastolic velocity, RI) were not found to correlate with semen quality. Conclusions: Testicular volume which has a close relation to the semen parameters could be used as a clinical prediction factor for the quality of semen.

The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses.

One hallmark of mesenchymal stem cells (MSCs) is the ability to differentiate into multiple tissue types which assists in tissue regeneration. Another hallmark of MSCs is their potent anti-inflammatory and immunomodulatory properties and the potential to treat inflammatory, immune-mediated, and ischemic conditions. In equine practice, MSCs have shown efficacy in the treatment of musculoskeletal disorders such as tendinopathy, meniscal tears and cartilage injury. However, there are many equine disease processes and conditions that may benefit from the immunomodulatory properties of MSCs. Examples include conditions associated with overwhelming acute inflammatory response such as systemic inflammatory response syndrome to chronic diseases characterized by a prolonged low level of inflammation such as equine asthma and recurrent uveitis. For the acute inflammatory response processes, there is often high morbidity and mortality with no effective immunomodulatory treatment to prevent the overwhelming synthesis of proinflammatory mediators. For chronic inflammatory disease processes, frequently long-term corticosteroid treatment is the therapeutic mainstay, with serious potential complications. Thus, there is an unmet need for alternative anti-inflammatory treatments for both acute and chronic illnesses in horses. While MSCs show promise for such conditions, much research is needed before a clinically safe and effective treatment will be available. Optimal MSC tissue source, patient vs. donor source (autologous vs. allogeneic) and cell growth conditions need to be determined for each problem. For immediate use, allogeneic MSC treatments is preferable, but immune tolerance and adequate safety require further study. MSC collection and cryopreservation from horses before they are injured or ill, whether from umbilical cord tissue, bone marrow or adipose might become more widespread. Once these fundamental approaches to treating specific diseases with MSCs are determined, the route of administration, dose and timing of administration also need to be studied. To provide a framework for development of MSC immunomodulatory treatments, this article reviews the current understanding of equine MSC anti-inflammatory and immunomodulatory properties and proposes how MSC therapy may be further developed to treat acute onset systemic inflammatory processes and chronic inflammatory diseases.

Hyper-Sialylated IgG M254, an Innovative Therapeutic Candidate, Evaluated in Healthy Volunteers and in Patients with Immune Thrombocytopenia Purpura: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics

Hyper-Sialylated IgG M254, an Innovative Therapeutic Candidate, Evaluated in Healthy Volunteers and in Patients with Immune Thrombocytopenia Purpura: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics

Daily Living Activities and Cognition in Aged Patients: Effect of Acute Systemic Diseases and Stroke on Leukoaraiosis.

Background: Acute Systemic Diseases (ASD) impact on extended leukoaraiosis (ExL-A) have been seldom described. We study the deterioration in daily life activities (DLA) and cognition associated with ASD events compared with the well-described impacts of stroke in patients with leu-koaraiosis (L-A).Methods: Cross-sectional surveys of aged adults from the emergency room after an acute event of ASD or stroke, hospitalized or receiving home care, were followed for one year. From 268 initial pa-tients 206 were included in the study, all with moderate to severe L-A (Fazekas 2 and 3). The Clinical Deterioration Rating (CDR) and the modified Rankin scale with structured interview were obtained one week previous to admission and after 3 and 12 months of evolution. Comparisons were conduct-ed within and between groups with nonparametric techniques.Results: We formed three groups of similar age, A: Inpatients with one Stroke, B: Inpatients with one ASD, and C: Outpatients with one ASD. A sudden deterioration in Rankin was evident in Group A, while in B and C impairment was progressive. Impairment in CDR was smooth in all groups while in Rankin it was always greater than in cognition (CDR). No differences were found in the associations between groups and risk factors, hypertension being the most frequent one.Conclusion: ASD in ExL-A causes a worsening of DLA and cognition similar to that observed in ExL-A with concomitant stroke indicating the need, in ageing patients, of differential diagnosis in or-der to achieve the best possible treatment.

Nonthyroidal Illness Syndrome and Thyroid Hormone Actions at Integrin αvβ3.

The nonthyroidal illness syndrome (NTIS) is a constellation of changes in circulating thyroid hormone levels that occur in euthyroid patients with acute or chronic systemic diseases. The changes that occur include a reduction in serum T3, an increase in serum rT3, and variable changes in circulating T4 levels. No consensus exists regarding therapeutic intervention for NTIS. We briefly review the published literature on the physiological actions of T4 and of rT3-hormones that until recently have been seen to have little or no bioactivity-and analyze the apparent significance of changes in circulating T4 and T3 encountered in the setting of NTIS in patients with cancer. In the case of T4, these actions may be initiated at a cancer or endothelial cell plasma membrane receptor on integrin αvβ3 or at the cytoskeleton. This review examines possible therapeutic intervention in NTIS in patients with cancer in terms of T4 reduction and T3 support. Evidence also exists that rT3 may support cancer. Prospective study is proposed of pharmacological reduction of normal or elevated T4 in cancer-associated NTIS. We also support investigation of normally circulating levels of T3 in such patients.

INHIBITORY ACTIVITY OF COBALT(II)–MORIN COMPLEX AGAINST THE REPLICATION OF DENGUE VIRUS TYPE 2

Dengue virus (DENV) is a significant pathogen emerging worldwide as a cause of infectious disease. Antidengue treatments are urgently required to control the emergence of dengue. DENV is a mosquito-borne disease responsible for acute systemic diseases and serious health conditions. DENVs were distributed in the tropical and sub-tropical areas and transmitted to humans by Aedes agypty and Aedes albopictus. Dengue vaccine or antiviral has not yet been clinically approved for humans, even though there have been great efforts toward this end. Antiviral activity against DENV is an important alternative for the characterization and development of drugs. Metal–organic compounds were reported to exhibit fungicidal, bactericidal, and antiviral activities its inhibitory activity was not significant, at high concentration it was more toxic to replicating cells than to stationary cell monolayers of Vero cells. The aim of this study is to investigate the antiviral effects of Cobalt(II)–Morin complex. This compound was further investigated for its inhibitory effect on the replication of DENV-2 in Vero cells. The replication of DENV was measured by enzyme-linked immunosorbent assay and the value of selectivity index (SI). SI was determined as the ratio of the 50% cytotoxic concentration (CC50) to the 50% inhibitory concentration (IC50). The IC50 value of the Cobalt(II)–Morin complex for DENV-2 was 3.08 µg/ml, and the CC50 value of the complex for Vero cells was 3.36 µg/ml; thus, the SI value was 1.09. The results of this study demonstrate the antidengue serotype 2 inhibitory activity of Cobalt(II)–Morin complex and its high toxicity in Vero cells. Further studies are not required before Co(II)–Morin can be applied in the treatment of DENV-2 infections.

Factor VII-Activating Protease: Hemostatic Protein or Immune Regulator?

Factor VII (FVII)-activating protease (FSAP) is a serine protease in plasma, which was initially described to play a role in coagulation by activation of FVII, independent of tissue factor, and in fibrinolysis by cleavage of single-chain urokinase. Recent studies, however, suggest that FSAP-mediated FVII cleavage is negligible and that FSAP may exert procoagulant functions via cleavage of tissue factor pathway inhibitor. Meanwhile, many substrates of FSAP have been identified, such as platelet-derived growth factor, basic fibroblast growth factor/epidermal growth factor, histones, and high-molecular-weight kininogen. FSAP has also shown to induce DNA released from dead cells. Given its propensity for autoproteolysis and degradation, studies on the activation and regulation of FSAP are difficult to perform. Recent animal studies suggest a role of FSAP in the pathogenesis of arteriosclerosis, vascular integrity and probably also in the regulation of coagulation initiation. This review will focus on the biochemical properties of FSAP, regulation of FSAP activation, and finally its role in vascular disease and acute systemic inflammatory diseases, such as sepsis.

ANTIVIRAL ACTIVITY OF COPPER(II)CHLORIDE DIHYDRATE AGAINST DENGUE VIRUS TYPE-2 IN VERO CELL

Infection of dengue virus (DENV) was number of globally significant emerging pathogen. Antiviral dengue therapies ar importantly needed to control emerging dengue. Dengue virus (DENV) is mosquito-borne arboviruses responsible for causing acute systemic diseases and grievous health conditions in humans. To date, there is no clinically approved dengue vaccine or antiviral for humans, even though there have been great efforts towards this end. Copper and copper compounds have more effective in inactivation viruses, likes an influenza virus and human immunodeficiency virus (HIV). Purpose in this project was investigated of Copper(II)chloride Dihydrate antiviral compound were further tested for inhibitory effect on the replication of DENV-2 in cell culture. DENV replication was measures by Enzyme linked Immunosorbent Assay (ELISA) with selectivity index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for compound. The maximal inhibitory concentration (IC50) of Copper(II)chloride Dihydrate against dengue virus type-2 was 0.13 μg/ml. The cytotoxic concentration (CC50) of compound against Vero cell was 5.03 μg/ml. The SI values for Copper(II)chloride Dihydrate 38.69. Result of this study suggest that Copper(II)chloride Dihydrate demonstated significant anti-DENV-2 inhibitory activities and not toxic in the Vero cells. Copper mechanisms play an important role in the prevention of copper toxicity, exposure to excessive levels of copper can result in a number of adverse health effects, as a result increased reactive oxygen species and oxidative damage to lipid, DNA, and proteins have been observed in human cell culture models or clinical syndromes of severe copper deficiency and inhibition was attributed to released cupric ions which react with cysteine residues on the surface of the protease.

Interleukin (IL-6) Immunotherapy.

Interleukin 6 (IL-6) is a prototypical cytokine for maintaining homeostasis. When homeostasis is disrupted by infections or tissue injuries, IL-6 is produced immediately and contributes to host defense against such emergent stress through activation of acute-phase and immune responses. However, dysregulated excessive and persistent synthesis of IL-6 has a pathological effect on, respectively, acute systemic inflammatory response syndrome and chronic immune-mediated diseases. The IL-6 inhibitor, tocilizumab, a humanized anti-IL-6 receptor antibody, is currently being used for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, and Castleman disease. Lines of recent evidence strongly suggest IL-6 blockade can provide broader therapeutic strategy for various diseases included in acute systemic and chronic inflammatory diseases.