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Αλέξανδρος Γ. Σφακιανάκης

Tuesday, November 10, 2020

Amelioration of Rheumatoid Arthritis by Anacardium occidentale via Inhibition of Collagenase and Lysosomal Enzymes

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Anacardium occidentale (cashew) has been used in the traditional system of medicine for curing many inflammatory disorders. The present study investigates the antiarthritic effects of cashew leaves extract using the rat model of FCA-induced rheumatoid arthritis. Arthritic rats were treated with 100 and 200 mg/kg b.w. ethanolic extract of cashew leaves. Animals were sacrificed at day 23, and before sacrificing the animals, gross pathological changes were observed. Histopathology of ankle joint was evaluated with hematoxylin and eosin staining, whereas the serum levels of C-reactive protein (CRP) were evaluated by the agglutination method. Inflammatory cells and other hematological parameters were assessed by employing an automated hemocytometer and chemistry analyzer. Rheumatoid factor (Rf) and lysosomal enzymes levels were determined in blood. Results indicated that A. occidentale significantly decreased the CPR levels, macroscopic arthritic score, and rheumatoid factor as compared to the diseased group. Histopathological evaluation showed significant attenuation in bone erosion, joint inflammation, and pannus formation by plant extract. Treatment with A. occidentale significantly suppressed the levels of acid phosphatase, β-galactosidase, β-glucuronidase, N-acetylglucosaminidase, and collagenase. Moreover, A. occidentale significantly raised the HB levels and RBCs counts which were found depleted in the diseased group. The raised counts of total leukocytes, platelets, neutrophils, lymphocytes, and monocytes were also significantly decreased by treatment with plant extract. Comparative analysis showed that higher dose of A. occidentale demonstrated superior amelioration of rheumatoid arthritis as compared to low dose. In conclusion, A. occidentale possesses significant antiarthri tic potential, which may be attributed to the suppression of lysosomal enzymes and collagenase levels.
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Three Cases of Anaplastic Thyroid Carcinoma Transformation and Leukocytosis during Lenvatinib Treatment

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Since 2015, the cancer treatment lenvatinib has been used for patients with advanced radioactive iodine- (RAI-) refractory thyroid differentiated cancer; however, the drug's long-term effects have not been fully investigated. We report three cases in which lenvatinib treatment initially improved the patients' conditions, although they all died approximately 2 months after leukocytosis due to very aggressive disease progression with anaplastic thyroid carcinoma transformation. Serum interleukin-6 (IL-6) was elevated in all three cases, and granulocyte-colony stimulating factor (G-CSF) was elevated in two cases. The patients had a similar clinical course, with multiorgan metastasis and aggressive disease progression. Even with advanced cancer, lenvatinib has provided control of the disease. However, as l ong-term use of lenvatinib grows, it is possible that similar cases will increase, and we report our findings as an alert to other clinicians.
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Two Cases of Severe Hypertension in JAK2 Mutation-Positive Myeloproliferative Neoplasms

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Background. Myeloproliferative neoplasms are a heterogeneous group of disorders resulting from the abnormal proliferation of one or more terminal myeloid cells—established complications include thrombosis and haemorrhagic events; however, there is limited evidence to suggest an association with arterial hypertension. Herein, we report two independent cases of severe hypertension in JAK2 mutation-positive myeloproliferative neoplasms. Case Presentations. Case 1: a 39-year-old male was referred to our specialist hypertension unit with high blood pressure (BP) (200/120 mmHg), erythromelalgia, and headaches. We recorded elevated serum creatinine levels (146 μM) and panmyelosis. Bone marrow biopsy confirmed JAK2-mutation-positive polycythaemia vera. Renal imaging revealed renal artery stenosis. Asp irin, long-acting nifedipine, interferon-alpha 2A, and renal artery angioplasty were employed in management. BP reached below target levels to an average of 119/88 mmHg. Renal parameters normalised gradually alongside BP. Case 2: a 45-year-old male presented with high BP (208/131 mmHg), acrocyanosis, (vasculitic) skin rashes, and nonhealing ulcers. Fundoscopy showed optic disc blurring in the left eye and full blood count revealed thrombocytosis. Bone marrow biopsy confirmed JAK2-mutation-positive essential thrombocytosis. No renal artery stenosis was found. Cardiac output was measured at 5 L/min using an inert gas rebreathing method, providing an estimated peripheral vascular resistance of 1840 dynes/s/cm5. BP was well-controlled (reaching 130/70 mmHg) with CCBs. Conclusions. These presentations highlight the utility of full blood count analysis in patients with severe hypertension. Hyperviscosity and constitutive JAK-STAT activation are amongst the proposed pathophysiology linking myeloproliferative neoplasms and hypertension. Further experimental and clinical research is necessary to identify and understand possible interactions between BP and myeloproliferative neoplasms.
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Circulating Irisin Levels in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

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Background and Aims. Previous studies have revealed the close relation of irisin with the occurrence and development of nonalcoholic fatty liver disease (NAFLD). A systematic review and meta-analysis were conducted to evaluate the association of circulating irisin levels and NAFLD. Methods. A systematic literature search of PubMed, Embase, Cochrane Library, Clinicaltrials.gov, WANFANG, CNKI, and CBM databases was performed for relevant articles till August 2020. The weighted mean difference (WMD) values and 95% confidence intervals (CIs) were estimated to compare the case-control studies and pooled results using meta-analysis. Results. The meta-analysis included 5 case-control studies with a total of 1087 people. The results revealed that the circulating irisin levels showed no significant difference between NAFLD and healthy groups ( (-12.53, 27.56) ng/ml, ). Subgroup analysis based on races showed that the average irisin levels were higher in the NAFLD group than in the healthy group ( (0.71, 26.34) ng/ml, ) in 4 Asian studies. Subgroup analysis based on disease severity from 3 Asian studies revealed that the average irisin levels were higher in the NAFLD group than in the healthy group ( (22.85, 27.51) ng/ml, and (22.85, 27.51) ng/ml, , respectively). Subgroup analysis including 3 studies from Asia suggested that the irisin levels were higher in mild NAFLD than in moderate-severe NAFLD ( (9.03, 14.32) ng/ml, ).Conclusion. The average irisin levels might be higher in the NAFLD group than in the healthy group in Asians. The irisin levels in the mild NAFLD group might be higher than those in the moderate-severe group in Asians. It is important to monitor the changing trend of irisin levels in predicting the course of NAFLD disease and its changes.
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The Short QTc Is a Marker for the Development of Atrial Flutter and Atrial Fibrillation

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A short QT interval has been difficult to define, and there is debate whether it exists outside of an extremely small group of individuals with inherited channelopathies and whether it predicts cardiac arrhythmias. The objective was to identify cases with short QT and their consequences. Our hospital ECG database was screened for cases with a QTc based on the Bazett formula (QTcBZT) of less than 340 ms. The QTc was recalculated using the spline (QTcRBK) formula, which more accurately adjusts for the heart rate and identifies cases based on percentile distribution of the QT interval. The exclusion criteria were presence of bundle branch block, arrhythmias, or electronic pacemakers. An age- and sex-matched cohort was obtained from individuals with normal QT intervals with the same exclusion criteria. There we re 28 cases with a short QTc (QTcRBK 
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Clinical Characterization of Ulcerative Colitis in Patients with Primary Sclerosing Cholangitis

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Objectives. The clinical/colonoscopic features of ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC), the prognostic impact of UC, and the utility of UC screening in PSC patients are unknown. We characterized UC associated with PSC and assessed UC's impact on the prognosis of PSC and the importance of colonoscopic UC screening in PSC patients. Methods. We retrospectively analyzed the cases of 77 patients treated for PSC at a single center (April 2000–July 2019). We reviewed the clinical/colonoscopic profiles of the concurrent UC patients and compared the clinical profiles, survival, and primary causes of death between the patients with/without UC (/). The details of all patients' colonoscopies were reviewed. Results. The concurrent UC group: 17 men, 18 women, diagnosed with PSC at the mean (SD) age of 36 (17) years; 21 patients (60%) had no UC symptoms. Colonoscopy revealed pancolitis in all patients, predominantly affecting the right-sided colon in 30 patients (86%). Lesions were scattered. Backwash ileitis (, 37%) and rectal sparing (, 51%) were observed. Most patients had mild UC; some had moderate or more severe UC (median Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score 2; range, 1–5). Ludwig's stage determined by liver biopsy did not correlate with the Mayo endoscopic score for UC. The patients with UC were diagnosed with PSC at a significantly younger age than those without UC (mean (SD), 36 [17] years vs. 55 [19] years, ) and had a significantly higher 5-year survival rate (97.1% vs. 70.5%, ). UC was detected in 19 of 34 asymptomatic patients (56%) who underwent colonoscopy screening. Conclusions. Our cohort's clinical/colonoscopic features of UC associated with PSC are more moderate or severe UC than previous cases. The coexist ence of UC might affect the prognosis of PSC. In this regard, colonoscopy in PSC patients is an important examination for determining prognosis. There is also asymptomatic UC in patients with PSC. In this regard, screening for colonoscopy in PSC patients is essential. When a diagnosis of PSC is made, immediate colonoscopy is a priority with UC complications in mind.
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GC-FID and Olfactometry-Assisted Assessment of Odors from Polymeric Foams under Normal and Repeated-Use Conditions

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Polymeric foams are the primary components of upholstered furniture, and their emissions play a decisive role in the acceptability of the final furniture product. This study is focused on passive emissions and odors from commercial foams under normal and repeated-use conditions. Six different types of foams, viz., highly elastic foam K5040, standard PU foam N5063, bonded polyurethane foam R100, viscoelastic foam V5020, self-extinguishing foam KF5560, and foam rubber, were used. The samples were collected at the intervals of 72 hours and 672 hours (28 days) to identify the odors due to chemical reactions in the material or slowly released due to its porous structure. Additionally, repeated-use studies were done to understand the effect of prolonged usage/natural ageing on emitted odors from the foams. The samp les were tested as per ČSN EN 13 725 (2005) and ISO 16000-6 (2011) criteria using GC-FID (gas chromatography-flame ionization detector) and olfactometry. The most unpleasant substance was found to be nonanal, with an average score of -4 (unpleasant). A total of 23 compounds were identified (5 unidentified) using olfactometry; however, only 11 of them were confirmed by GC-FID-based testing. Any new compound or increase in odor intensity was not observed in long-term measurements and simulated repeated-use conditions.
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Target Enzymes Considered for the Treatment of Alzheimer’s Disease and Parkinson’s Disease

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Various amyloidogenic proteins have been suggested to be involved in the onset and progression of neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). Particularly, the aggregation of misfolded amyloid-β and hyperphosphorylated tau and α-synuclein are linked to the pathogenesis of AD and PD, respectively. In order to care the diseases, multiple small molecules have been developed to regulate the aggregation pathways of these amyloid proteins. In addition to controlling the aggregation of amyloidogenic proteins, maintaining the levels of the proteins in the brain by amyloid degrading enzymes (ADE; neprilysin (NEP), insulin-degrading enzyme (IDE), asparagine endopeptidase (AEP), and ADAM10) is also essential to cure AD and PD. Therefore, numerous biological mol ecules and chemical agents have been investigated as either inducer or inhibitor against the levels and activities of ADE. Although the side effect of enhancing the activity of ADE could occur, the removal of amyloidogenic proteins could result in a relatively good strategy to treat AD and PD. Furthermore, since the causes of ND are diverse, various multifunctional (multitarget) chemical agents have been designed to control the actions of multiple risk factors of ND, including amyloidogenic proteins, metal ions, and reactive oxygen species. Many of them, however, were invented without considerations of regulating ADE levels and actions. Incorporation of previously created molecules with the chemical agents handling ADE could be a promising way to treat AD and PD. This review introduces the ADE and molecules capable of modulating the activity and expression of ADE.
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An Evaluation of the Antibacterial Properties of Tormentic Acid Congener and Extracts From Callistemon viminalis on Selected ESKAPE Pathogens and Effects on Biofilm Formation

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ESKAPE pathogens, namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, are responsible for a majority of all healthcare-acquired infections (HAI). The bacteria cause nosocomial infections in immunocompromised patients. Extracts from Callistemon viminalis have been shown to have antibacterial, antifungal, and anti-inflammatory activities. Tormentic acid congener, a pentacyclic triterpene saponin, was isolated from C. viminalis leaves. This study aimed to investigate the antibacterial effects of tormentic acid congener and leaf extracts on biofilm formation by A. baumannii, S. aureus, S. pyogenes, and P. aeruginosa. The antibacterial effects were determined by the microbroth dilution method, and ciprofloxacin was u sed as the standard antibacterial drug. Biofilm formation and detachment assays were performed using crystal violet staining. Production of extracellular polymeric DNA and polysaccharides from biofilms was also determined. Tormentic acid congener showed time-dependent antibacterial activity against P. aeruginosa with a MIC of 100 µg/ml and caused significant protein leakage. Antibacterial activity was found when tormentic acid congener was tested against both S. aureus and P. aeruginosa. The MICs were found to be 25 µg/ml and 12.5 µg/ml for P. aeruginosa and S. aureus cells, respectively. S. pyogenes was found to be susceptible to tormentic acid congener and the hydroethanolic extract with an MIC of 100 µg/ml and 25 µg/ml, respectively. A. baumannii was found not to be susceptible to the compound or the extracts. The compound and the extracts caused a significant decrease in the biofilm extracellular polysaccharide content of S. pyogenes. The extracts and tormentic ac id congener caused detachment of biofilms and decreased the release of extracellular DNA and capsular polysaccharides from biofilms of P. aeruginosa and S. aureus. Tormentic acid congener and extracts, thus, have significant antibacterial and antibiofilm activities on these selected ESKAPE bacteria and can act as source lead compounds for the development of antibacterial triterpenoids.
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Efficacy and Safety of Acupuncture against Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

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Objective. To determine the effectiveness and safety of acupuncture for chemotherapy-induced peripheral neuropathy. The review has been registered on the "PROSPERO" website; the registration number is CRD42020151654. Methods. A comprehensive literature search was performed on 7 electronic databases from the time of inception to March 2020. RCTs studies on acupuncture for CIPN compared with medication or sham acupuncture were included. Statistical analysis was carried out using RevMan 5.3. Results. In total, 19 RCTs covering 1174 patients were enrolled. The results showed that acupuncture significantly increased the effective rate of CIPN compared with medicine and sham acupuncture. And acupuncture had a good effect on the recovery of nerve conduction velocity and improving pain. Among the acupoints inv olved in the treatment of CIPN, LI4, LI11, ST36, EX10 (Bafeng), and EX-UE 9 (Baxie) were the most commonly used. Conclusion. The use of acupuncture in the management of CIPN is safe and effective. The most used acupoints for CIPN are LI4, LI11, ST36, EX10 (Bafeng), and EX-UE 9 (Baxie).
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Type 2 Diabetes Mellitus and Chronic Heart Failure with Midrange and Preserved Ejection Fraction: A Focus on Serum Biomarkers of Fibrosis

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As myocardial fibrosis might be an important contributor to the association of diabetes mellitus with left ventricular (LV) dysfunction and chronic heart failure (HF), we investigated the profile of some proinflammatory, profibrotic biomarkers in patients with type 2 diabetes mellitus (T2DM) at various stages of the cardiovascular disease continuum from absence of clinic since and symptoms to HF with preserved (HFpEF) and midrange ejection fraction (HFmrEF). Material and Methods. Sixty-two patients with T2DM (age 60 [55; 61]), 20 patients without clinical manifestations of HF and 2 groups with clinical manifestations of stable HF, 29 patients with HFpEF, and 13 patients with HFmrEF, were included in the study. The control group consisted of 13 healthy subjects and normal BMI. All patients underwent transthora cic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), highly sensitive C-reactive protein (hsCRP), soluble suppression of tumorigenesis-2 (sST2), galectin-3, C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1). Results. Patients with HFmrEF had higher values of LV volumetric parameters, indexed parameters of LV myocardial mass (LVMM), and higher concentrations of Nt-proBNP (all ). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF ( and , respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF ( and , respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area (,), PIIINP, TIMP-1, and LV end-diastolic volume ( and and and , respectively). Conclusion. The dynamics at various stages of the cardiovascular disease continuum in the serum fibrosis markers may reflect an increase in fibrotic and decrease in antifibrotic processes already at the preclinical stage of HF. At the same time, the changes found in the circulating procollagen levels may indicate a shift in balance towards type I collagen synthesis in HFmrEF compared with HFpEF.
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Ventricular Rupture due to Myocardial Infarction without Obstructive Coronary Artery Disease

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An 87-year-old woman presenting with myocardial infarction and ST-segment elevation in the electrocardiogram suffered from pericardial effusion due to left ventricular rupture. After ruling out obstructive coronary artery disease and aortic dissection, she underwent cardiac surgery showing typical infarct-macerated myocardial tissue in situ. This case shows that even etiologically unclear and small-sized myocardial infarctions can cause life-threatening mechanical complications.
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