Induction of apoptosis and inhibition of growth of human hepatoma HepG2 cells by heparin

BACKGROUND/AIMS: Apoptotic and anti-proliferative effects of heparin on a number of cancers have been described. There have been no studies analyzing the effect of heparin on human hepatoma cells. The aim of this study was to investigate the effect of heparin on human hepatoma cell line, HepG2. METHODOLOGY: HepG2 cell line was cultured with different concentrations of heparin. Colony count, viability assay, percentage of the apoptosis and proliferative index were assessed at the end of the 7th day. Trypan blue was used to assess viability. Apoptosis and proliferative indexes were assessed by flow-cytometry. RESULTS: Hepatoma cells were arrested at the G0/G1 phase with heparin incubation and proliferative indexes decreased significantly in 20, 40 and 80 U/mL of heparin concentrations in comparison with the control (36 +/- 1%, 30 +/- 5% and 29 +/- 8% vs. 44 +/- 1%, p < 0.01). Flow cytometry revealed a statistically significant increase in apoptosis in groups incubated with 40 and 80 U/mL of heparin in comparison with the control (39 +/- 26% and 58 +/- 18% vs. 0.83 +/- 1.3%, p < 0.01). Colony counts per well and viable cells per microL decreased significantly in 80 U/mL of heparin. CONCLUSIONS: Heparin leads to a significant anti-proliferative and an apoptotic effect on human hepatoma cells in vitro.     

Treatment of spastic esophageal motility disorders

Treatment of spastic motility disorders continues to be challenging.Therapeutic options remain limited due in part to our lack of understanding of the pathophysiology and significance of these disorders. Furthermore, most of therapeutic trials to date are hampered by the poorly designed nature of the study, including the small size of the trials and the lack of placebo arm. Most of the available information suggests that there seems to be an important dissociation between symptoms (chest pain/dysphagia) and esophageal dysmotility. Drug treatment aimed at visceral sensitivity seems more effective in relieving symptoms than spasmolytic medications. Recent trials with Botox, nitric oxide derivatives, and SSRIs offer promising results. Rigorous study design that includes large placebo-controlled trials is needed in this area.     

Usefulness of M-mode echocardiography in the diagnosis of heart failure

The utility of M-mode echocardiography in the diagnosis of heart failure (HF) was evaluated in a study of 70 patients with suspected HF (26 men and 44 women) and 63 control persons (26 men and 37 women), all aged 45-74 years. The patients were classified according to the certainty of HF diagnosis using the Boston criteria: 27 patients were defined as 'unlikely' to have HF, 19 as having 'possible' HF, and 24 as having 'definite' HF. In calculations of the sensitivities and specificities for echocardiographic variables in detecting 'definite' HF, the 95% confidence limits in the control group were used as cut-off point values. Sensitivities thus attained were 91% for mitral valve E point-septal separation (EPSS), 73% for left ventricular (LV) fractional shortening (FS), and 64% for peak rate of increase of LV diameter (PLR), respectively, and the specificities were 73, 88, and 78%, respectively. When EPSS, FS and PLR were all normal, the likelihood of 'definite' HF was as low as 7%. We conclude that M-mode echocardiography is actually a useful method in the diagnostic evaluation of patients with suspected HF, and it is more reliable in excluding than confirming the presence of HF.     

Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?

In this study, we report a large family cluster consisting of 29 genetically related patients hospitalized with coronavirus disease‐2019 (COVID‐19). We sought to determine the clinical characteristics relevant to the clinical course of COVID‐19 by comparing the family cluster to unrelated patients with SARS‐CoV‐2 infection so that the presence of potential determinants of disease severity, other than traditional risk factors previously reported, could be investigated. Twenty‐nine patient files were investigated in group 1 and group 2 was created with 52 consecutive patients with COVID‐19 having age and gender compatibility. The virus was detected for diagnosis. The clinical, laboratory and imaging features of all patients were retrospectively screened. Disease course was assessed using records regarding outcome from patient files retrospectively. Groups were compared with respect to baseline characteristics, disease severity on presentation, and disease course. There was no difference between the two groups in terms of comorbidity and smoking history. In terms of inhospital treatment, use differed not significantly between two groups. We found that all 29 patients in the group 1 had severe pneumonia, 18 patients had severe pneumonia. Hospitalization rates, length of hospital stay, and transferred to intensive care unit were found to be statistically significantly higher in the group 1. In the present study, COVID‐19 cases in the large family cluster were shown to have more severe disease and worse clinical course compared with consecutive patients with COVID‐19 presenting to the same time. We believe further studies into potential genetic mechanisms of host susceptibility to COVID‐19 should include such family clusters.     

Primary dural lymphoma: A novel concept of heterogeneous disease

Spinal primary dural lymphoma (PDL) is uncommon with a total of 37 previous well‐documented cases reported, including one diagnosed in the authors' institution. More recently we encountered an additional case of spinal PDL that, similarly to our previous case, was grade 1–2 follicular B‐cell PDL. Our two cases were diagnosed over a 3‐year interval in a 72‐year‐old female and a 74‐year‐old male, respectively. An exhaustive literature review on PDL was performed consequently to reveal that: (i) spinal and cerebral sites of involvement by PDL are constantly mutually exclusive; and (ii) unlike cerebral PDL, which is usually of marginal zone B‐cell type, only two of the 38 cases of spinal PDL were diagnosed as such, diffuse large B‐cell lymphoma being the most commonly encountered type in the spine. This divergence infers that, in contrast to the prevailing concept that PDL is a unique disease group, PDL appears to be rather heterogeneous with a difference in predilection of lymphoma type for the anatomical site of dural involvement. Such a site‐specific lymphoma‐type predilection phenomenon, well‐recognized in other organ systems, has not been acknowledged in PDL. This report brings new insights into PDL, and may contribute to a better understanding of nervous system pathophysiology and lymphoma classification.     

Droplet fluid infusion into a dust layer in relation to self-cleaning

Wettability of a droplet liquid on a dusty hydrophobic plate is considered and the fluid infusion into the dust layer is studied pertinent to dust removal from the hydrophobic surfaces via rolling/sliding droplets. Influence of droplet hydrostatic pressure on the fluid infusion into dust layer is also investigated towards exploring the dust removal mechanisms. Environmental dust characteristics are evaluated and their interface with the droplet fluid is assessed. Sets of experiments are carried out to examine: (i) droplet fluid infusion into the dust layer, (ii) droplet fluid cloaking of dust, and (iii) evaluate the weight gain of the dust particles during cloaking. The findings reveal that droplet fluid (water) spreads onto the dusty surface and infuses on the dust particles. Cloaking velocity decays sharply with time and the weight gain of the dust particles is about 17% of the original dust weight after cloaking. The dust particles have a large area of nano-size open-pores-sites on the surface; however, capillary diffusion through these sites is limited with shallow depths and the weight gain of a dust particle via capillary diffusion is about 1% of the particle weight. The maximum infusion depth of the droplet fluid in the dust layer is about 74 μm, which is slightly less than the dust layer thickness on the surface. The rolling droplet picks up all the dust from the 150 μm thick dust layer on the surface.

Wettability of a droplet liquid on a dusty hydrophobic plate is considered and the fluid infusion into the dust layer is studied pertinent to dust removal from the hydrophobic surfaces via rolling/sliding droplets.     

Optimizing therapy in inflammatory arthritis: prediction of relapse after tapering or stopping treatment for rheumatoid arthritis patients achieving clinical and radiological remission

This study aims to assess clinical, lab/immunological or imaging (joint ultrasonography) markers able to predict disease relapse in RA patients in sustained remission when tapering or stopping their treatment. One hundred fifty-seven RA patients in clinical remission (DAS-28 <2.6 for >6 months), receiving treatment with sDMARDs and bDMARD therapy, were randomly allocated into any of five groups: Group 1: continue full dose DMARDs and taper biologic therapy by 50 % (31 patients); Group 2: taper both DMARDs and biologic therapy dose by 50 % (32 patients); Group 3: taper DMARDs by 50 % and stop biologic therapy (31 patients); Group 4: stop both DMARDs and biologic therapy (31 patients); Group 5: continue medications without change (31 patients). Forty joints were assessed ultrasonographically (DAS-28 joints + ankles + metatarsophalangeal joints) and prospectively monitored for 12 months. The primary endpoint was sustained remission for 12 months. Patients were considered as having a relapse when the DAS-28 score was >3.2 and anti-rheumatic treatment was escalated. The frequency of relapse was 41.9 % in Group 1, 59.3 % in Group 2, 67.7 % in Group 3, 77.4 % in Group 4 and 6.5 % in Group 5. Relapse rates were significantly higher in patients whose ultrasound scores raised within 3 months of stopping their medications (P < 0.001 for both GS and PD scores). Cox regression identified ACPA positivity (at baseline) and progression of functional disability (at 2 months) as predictors for relapse. Tapering therapy is feasible in RA patients. Tailored dynamic approach is advised. Joint ultrasonographic assessment, ACPA positivity and worsening functional disability predicted relapse within a short term after discontinuation of the treatment. RA patients whose DAS-28 score was <2 were more likely to remain in remission.