scholarly journals Effect of hydroxychloroquine on SARS-CoV-2 viral load in patients with COVID-19

Author(s):  
Klinger Soares Faíco-Filho ◽  
Danielle Dias Conte ◽  
Luciano Kleber de Souza Luna ◽  
Joseane Mayara Almeida Carvalho ◽  
Ana Helena Sitta Perosa ◽  
...  

ABSTRACTBackgroundSome studies have shown that hydroxychloroquine (HCQ) is an effective drug in reducing the in vitro replication of SARS-CoV-2. However, the in vivo effect of HCQ still unclear. This study aims to evaluate viral load clearance in patients with COVID-19 who underwent HCQ treatment in comparison with a control group that did not receive the drug.MethodsThis prospective study comprised consecutive viral load measurements in patients with COVID-19 hospitalized with a moderate illness. Patients received 400 mg of HCQ every 12 hours for 10 days according to the medical decision. Nasal swab samples were collected at the 1st, 7th, and 14th days of the admission.Results155 samples were collected from 66 patients with COVID-19 (60% female), with a median age of 58 years. The viral load between studied groups, assumed as a semiquantitative measure of cycle threshold (Ct) values, presented no significant difference within the three consecutive measures (ΔCt) (p>0.05). We also analyzed the ΔCt viral load at different intervals of sample collection (Δt <7; 7-12 and >12 days) without significant differences at any ΔCt (p>0.05).ConclusionIn this study, we did not observe any change in viral load in vivo with the use of HCQ.SummaryWe evaluate viral load clearance in patients with COVID-19 who took hydroxychloroquine (HCQ) for treatment and those who not. Prospective viral load measurements have shown any change in viral load in vivo with the use of HCQ.

Materials ◽  
2018 ◽  
Vol 11 (12) ◽  
pp. 2520 ◽  
Author(s):  
Eun-Bin Bae ◽  
Ji-Hyun Yoo ◽  
Sung-In Jeong ◽  
Min-Su Kim ◽  
Youn-Mook Lim ◽  
...  

This study aimed to evaluate the titanium (Ti) implants coated with collagen type Ⅰ crosslinked using gamma-irrigation or glutaraldehyde (GA). The in vitro surface observations, quantification assay, and cell studies using human mesenchymal stem cells (hMSCs) were conducted. For in vivo experiments, the implants were divided into three groups and inserted into the rat tibias: control group (non-treated Ti implant), GA group (Ti implants coated with GA-crosslinked collagen) and 25 kGy group (Ti implants coated with gamma-radiation-crosslinked collagen at dose of 25 kGy). The animals were sacrificed at 4 weeks after implantation and the tissue sections were obtained. New bone volume (mm3) and bone-to-implant contact (BIC, %) within the region of interest (ROI) was measured. The in vitro results showed the highest osteogenic differentiation and levels of osteogenesis-related gene expressions in the 25 kGy group without cytotoxicity. The new bone volume of GA group was significantly higher than the control (p < 0.05). In the result of the BIC, the 25 kGy group was significantly higher than the control (p < 0.05). However, there was no significant difference between the experimental groups. Within the limitations of this study, Ti implant coated with gamma-radiation-crosslinked collagen has potential utility without side effects from chemical agents.


2017 ◽  
Vol 29 (1) ◽  
pp. 131
Author(s):  
T. Fujikawa ◽  
C. Kubota ◽  
T. Ando ◽  
S. Imamura ◽  
M. Tokumaru ◽  
...  

Carboxylated poly-l-lysine (CPLL) is an ampholytic polymer compound, and it is obtained by converting 65% amino groups to carboxyl groups after synthesising ε-poly-l-lysine aqueous solution and succinic anhydride. CPLL has cryoprotective property similar to antifreeze protein, and addition of CPLL into cryopreservation medium improves the post-thaw survival rate of cells and embryos. In this research, we examined the effectiveness of CPLL as a bovine germ cell cryoprotective material. In experiment 1 (in sperm), the conventional cryopreservation medium used for control group was consisted of 6.5% (vol/vol) glycerin, and the cryopreservation medium used for CPLL group was consisted of 3.25% (vol/vol) glycerin and 0.5% CPLL (wt/vol). The post-thaw survival and motility were assessed by using Sperm Motility Analysis System (DITECT Corp., Tokyo, Japan). There was no significant difference for post-thaw survival rate and motility (control v. CPLL; 98.8% v. 96.6% and 69.7% v. 62.2%, respectively). Artificial insemination was carried out in 65 cows (control v. CPLL; 34 v. 31), and the conception rate of the CPLL group was higher than that of the control group (80.6% v. 67.6%; P = 0.23). In experiment 2 (embryos), the conventional cryopreservation medium used for control group was consisted of 5% (vol/vol) ethylene glycol and 6% (vol/vol) propylene glycol in PBS. In the CPLL group, 7% (wt/vol) CPLL was added to the conventional medium. In vitro fertilization embryos were cryopreserved at Day 7 and Day 8. There was no significant difference in survival rate at 0, 24, and 48 h and hatched rate until 72 h after thawing (control v. CPLL: 93.6% v. 93.2%, 69.0% v. 64.7%, 56.1% v. 56.3%, 12.9% v. 10.2%, respectively). Embryos obtained by superovulation treatment and in vivo fertilization at Day 7 were cryopreserved using above 2 media, and transferred non-surgically into synchronized recipient cows (1 embryo per animal). Embryo transfer (ET) was carried out in 81 cows (control v. CPLL: 31 v. 50), and recipients were diagnosed for pregnancy ultrasonically 50 days after embryo transfer. Conception rate of CPLL group was higher than control group (50.0% v. 29.0%; P = 0.063). In both experiments, the significant differences between control group and CPLL group were determined by chi-squared test. The effectiveness of CPLL in cells and embryos has been reported; however, there is no report using CPLL in bovine germ cells. In this research, CPLL improved the conception rate of AI and ET, probably due to its low toxicity and protection of the cell membrane. These results suggest that CPLL is available as a new cryoprotective material for bovine sperm and embryo in slow freezing methods.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3902-3902
Author(s):  
Bao-An Chen ◽  
Cheng-Yin Huang ◽  
Xiao-Ping Pei ◽  
Chong Gao ◽  
Jia-Hua Ding ◽  
...  

Abstract This study was aimed to investigate functions of glycosylation cooled rabbit platelets in vivo and in vitro and the method to store cold platelets with UDP-gal. We collected rabbit heart blood, prepared concentrated platelet suspensions in a normal way to which we added UDP-Gal, and then stored them for ten days in 4° refrigerator. Thereafter platelet counts, mean platelet volume, platelet distributing width, platelet aggregation function, the activity to urge coagulation including PF3aT and APCT and apoptosis were determine- d. Meanwhile, survival time in vivo was tested after cold-stored rabbit platelets labeled with Cr51 were transfused into rabbits. Rabbit ear bleeding time and percentage plate recovery(PPR) were determined 1 hour and 24 hour after they were transfused into rabbit thrombocytopenia model. Results show that there was not significant difference in PLT counts, MPV, PDW, PF3aT and APCT between UDP-Gal cold-stored platelet group and fresh platelet group(p>0.05). On the contrary, platelet counts decreased significantly, MPV, PDW jumped and PF3aT and APCT went down in cold control group compared to fresh platelet group(p<0.01). Apoptosis increase in UDP-Gal cold-stored platelet group compared with fresh platelet group(p<0.05), but was significantly lower than that in cold control group(p<0.01). Although PagT(inducing reagent: C-PG) decreased, it could still be above 50% of fresh platelets. Survival time in rabbit vivo was close between UDP-Gal cold-stored platelet group and fresh platelet group(p<0.05). Survival rate seventy-two hours after transfusion in fresh platelet group, UDP-Gal cold-stored platelet group and cold control group was 57.5%±7.2%,50.3%±6.3% and 0.1%±0.1% respectively. Rabbit ear bleeding time was significantly shortened after transfusion of galactosylation cooled rabbit platelet (p<0.01), In contrast, it had less change in cold control group(p>0.05). PPR was 66.1%±0.5%,47.8%±0.6%;60.9%±0.3%,41.6%±0.4%;47.7%±0.5%,9.4%±0.5% respectively in fresh platelet group, UDP-Gal cold-stored platelet group and cold control group. PPR after transfusion of galactosylation cooled rabbit platelet had no statistical difference compared with that of fresh platelet group(p>0.05), and they in both groups were much higher than that in cold control group(p<0.01). Conclusion: Galactosylation can improve functions of cooled rabbit platelets in vivo and in vitro. and prolong the storage time of them.


Author(s):  
Parvin Dorfeshan ◽  
Marefat Ghaffari Novin ◽  
Mohammad Salehi ◽  
Fatane Farifteh

Background: The expression of miR-302 over the period of early embryogenesis could possibly regulate the maternal transcript clearance. Zygotic transcription activation is mostly related to maternal messages degradation. Objective: In this study, the effects of in-vitro maturation technique (IVM) on the expression of miR-302 in human embryo produced from immature and mature human oocytes (matured in vitro and in vivo, before sperm exposure) obtained from females under gonadotrophin therapy were evaluated for assisted reproduction. Materials and Methods: Immature oocytes were cultured in vitro. The injection of oocytes-producing polar bodies was given using fresh sperm. Then, the embryo quality score was assessed in the IVM group compared with the control group. In both the groups, embryos with normal morphology were included in the molecular study. Only one blastomere was removed from three-day embryos and then the embryos were frozen. The expression of miR-302 in embryos was measured through quantitative realtime polymerase chain reaction. Results: Our data showed a significant reduction of miR-302 expression in the IVM group vs. the control group (p = 0.02). The embryo quality score showed a significant difference between the two groups (p = 0.01). Conclusion: The present study demonstrated that the IVM process had a negative effect on the expression level of miR-302 in human pre-implantation embryos. Considering the major role of expression miR-302, a reduced potential in miR-302 expression could be related to a decrease in the early embryonic development.


GYNECOLOGY ◽  
2018 ◽  
Vol 20 (5) ◽  
pp. 46-51 ◽  
Author(s):  
M I Yarmoliskaya ◽  
M A Petrosyan ◽  
M S Florova ◽  
A S Molotkov ◽  
A S Denisova ◽  
...  

Introduction. The chronic, progressive, recurrent nature of the endometriosis results new avenues of targeted therapy for genital endometriosis with high therapeutic efficacy and minimal side effects must be explored. Nowadays, the standard of prolonged specific therapy for endometriosis is the dienogest 2 mg daily, which has already been proven to be effective in vitro, in vivo and in clinical practice. Purpose: to evaluate the effectiveness of new types of targeted pathogenetic therapy for endometriosis on the model of endometriosis in rats compared to dienogest and without treatment. Materials and methods. Endometriosis was induced on 69 Wistar rats by autotransplantation of uterine fragments onto the inner surface of the abdominal wall. After 14 days, the heterotopies had been measured by laparoscopy and then rats were randomized of into one of 6 experimental groups (dienogest, letrozole, cabergoline, metformin, vitamin D, melatonin) or a control group. All drugs were administered daily orally for three weeks, after which an autopsy and re-measuring of the size of endometrial implants were performed. Results. The most pronounced decrease in the size of endometrial implants was observed in the group of animals treated with dienogest (complete resorption - 48%, regression - 48%, without dynamics - 4%) and letrozole (complete resorption - 44%, regression - 56%) without the statistically significant difference between groups. In other groups, a significant decrease in the size of endometrial implants was demonstrated compared with the control, without a statistically significant difference between the groups. Findings. The presented study confirms the absence at the present time of oral drugs for the treatment of endometriosis, comparable in efficacy and safety with dienogest. Further research are needed to evaluate the different combinations of dopamine agonists, biguanides, vitamin D, melatonin as the supplement to the classic hormone-modulating therapy for endometriosis or as monotherapy in patients with contraindications to standard hormone therapy.


2005 ◽  
Vol 127 (7) ◽  
pp. 1168-1175 ◽  
Author(s):  
Ei Yamamoto ◽  
Daisuke Kogawa ◽  
Susumu Tokura ◽  
Kozaburo Hayashi

The effects of frequency or duration of cyclic stress on the mechanical properties of collagen fascicles were studied by means of in vitro tissue culture experiments. Collagen fascicles of approximately 300μm in diameter were obtained from rabbit patellar tendons. During culture, cyclic stress having the peak stress of approximately 2MPa was applied to the fascicles at 1Hz for 1hour∕day (1Hz-1h group), at 1Hz for 4hours∕day (1Hz-4h group), or at 4Hz for 1hour∕day (4Hz-1h group). The frequency of 4Hz and the duration of 1hour∕day are considered to be similar to those of the in vivo stress applied to fascicles in the intact rabbit patellar tendon. After culture for 1 or 2weeks, the mechanical properties of the fascicles were determined using a micro-tensile tester, and were compared to the properties of non-cultured, fresh fascicles (control group) and the fascicles cultured under no load condition (non-loaded group). The tangent modulus and tensile strength of fascicles in the 4Hz-1h group were similar to those in the control group; however, the fascicles of the 1Hz-1h and 1Hz-4h groups had significantly lower values than those of the control group. There was no significant difference in the tensile strength between the 1Hz-1h and non-loaded groups, although the strength in the 1Hz-4h group was significantly higher than that of the non-loaded group. It was concluded that the frequency and duration of cyclic stress significantly affect the mechanical properties of cultured collagen fascicles. If we apply cyclic stress having the frequency and duration which are experienced in vivo, the biomechanical properties are maintained at control, normal level. Lower frequencies or less cycles of applied force induce adverse effects.


1998 ◽  
Vol 5 (4) ◽  
pp. 499-502 ◽  
Author(s):  
Vellalore N. Kakkanaiah ◽  
Emmanuel A. Ojo-Amaize ◽  
James B. Peter

ABSTRACT The CC or β-chemokines MIP-1α, MIP-1β, and RANTES are the primary components of human immunodeficiency virus type 1 (HIV-1)-suppressive soluble factors in vitro. We studied the relationship between the concentrations of MIP-1α, MIP-1β, and RANTES in plasma and HIV viral load in HIV-infected subjects. The HIV-positive patient group (n = 140) had significantly lower concentrations of all three β-chemokines (MIP-1α,P < 0.0005; MIP-1β, P < 0.005; RANTES, P < 0.0005) than the control group (n = 58 for MIP-1α, n = 27 for MIP-1β, and n = 59 for RANTES). In addition, we divided the patient group into three subgroups (high, moderate, and low) based on the number of HIV-1 RNA copies in the plasma (as measured by quantitative HIV RNA PCR). Again, all three subgroups had significantly lower concentrations of the β-chemokines than the HIV-negative control group. However, there was no significant difference in plasma β-chemokine concentrations among the three subgroups within the patient group (P < 0.3). Although our results demonstrate that HIV-infected individuals had significantly lower concentrations of circulating β-chemokines than healthy uninfected control subjects, we found no correlation between the concentrations of β-chemokines in plasma and HIV-1 viral load in HIV-infected individuals.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4106-4106
Author(s):  
Ingrid Korakas ◽  
Darlene Guillen ◽  
Erika Martin ◽  
Mikael Tranholm ◽  
Thomas Barnett ◽  
...  

Abstract P-selectin, a member of the selectin family, is a vascular cell adhesion molecule. It is expressed and stored in alpha granules of platelets and in Weibel-Palade bodies of endothelial cells, and upon activation, P-selectin is translocated/transferred to the membrane surface. A key function of the P-selectin is to mediate leukocyte, lymphocyte and platelet interactions in inflammation and possibly in the thrombus formation. A soluble variant, S-Psel, comprising the extracellular domain of P-selectin, has been identified in healthy individuals, but is markedly elevated in patient with vascular disorders. Recent work on S-Psel suggested that S-Psel may play a role in hemostasis/coagulation through the generation of procoagulant TF-bearing microparticles (MP), and therefore, has potential in treating patients with the bleeding disorders, like hemophilia. The aim of this study is to verify studies reporting that S-Psel exhibits in vitro and in vivo pro-coagulant activity. S-Psel and S-Psel-Fc (IgG) fusion were purchased commercially or prepared at Novo Nordisk Research US (NNRUS) and their biological activity was verified by P-selectin/Pselectin glycoprotein ligand-1(PSGL-1) interaction in vitro. The clotting times of human whole blood and plasma treated with S-Psel or S-Psel-Fc, or with an irrelevant human IgG control protein, were measured by thromboelastography and aggregometry respectively. After up to 8 hours of incubation with S-Psel and S-Psel-Fc at a concentration of 15ug/ml, we found no significant difference between samples treated with S-Psel, S-Psel-Fc and the IgG controls. The ability of S-Psel to generate TF-bearing microparticles in human whole blood was examined in a FXa substrate cleavage assay; however, no significant difference in cleavage was observed. Finally, we evaluated S-Psel in vivo. Hemophilia A mice were injected with recombinant mouse S-Psel-IgG or S-Psel-Fc (IgG) at the concentration of 1.2 mg/Kg body weight and human IgG was used as control. As suggested from published results, the effect of S-Psel was determined 6 h after the treatment. Contrary to previous reports, the results revealed no significant difference in bleed time and blood loss between the experimental and control group. In conclusion, we were unable to demonstrate the procoagulant activity of S-Psel in our laboratory either in vitro or in vivo.


1989 ◽  
Vol 61 (02) ◽  
pp. 175-177 ◽  
Author(s):  
D A Tsakiris ◽  
G A Marbet ◽  
P E Makris ◽  
L Settas ◽  
F Duckert

SummaryLupus anticoagulants (LA) are IgG or IgM antibodies against phospholipids which in vivo represent an important thrombophilic factor despite their in vitro anticoagulant activity. We investigated the fibrinolytic system of 20 patients with connective tissue disease and positive LA, compared to a control group of 24 age- and disease-matched patients without LA. There was no statistically significant difference of alpha2-antiplasmin, plasminogen, fibrinogen, t-PA activity, D-dimers and heparin cofactor II, between the two groups. Although t-PA was uniformly low in both groups, plasminogen activator inhibitor activity (PAI) was significantly higher in LA cases (p <0.001). Increased PAI levels represent an inhibitory factor of the fibrinolytic defense mechanism, which together with other functional deviations may contribute to the thrombophilic tendency of LA patients.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii42-iii42
Author(s):  
X Ni ◽  
Y Qu ◽  
J Wang ◽  
F Chen ◽  
H Cai ◽  
...  

Abstract BACKGROUND TMZ, is the first line chemotherapeutic drug for glioma, and drug resistance is one of the most important reasons for glioma treatment failure. Our previous studies have found that: 1) Type I interferon (IFN) could reverse the resistance of TMZ by inhibiting NF-κB activity, and down-regulating the expression of MGMT in vivo and in vitro; 2) IFN-α could significantly improve chemtherapeautic effect of TMZ for GBM patients. We aim to investigate the therapeutic effect of a cocktail chemotherapy regimen combining temozolomide (TMZ)- Levetiracetam(LEV) - interferon (IFN) on human glioma U138 and U251 subcutaneous xenograft tumor. MATERIAL AND METHODS 30 xenograft tumors were established by subcutaneously injecting 1×106 glioma cells into the right flank of 4-week-old female BALB/C nude mice and then randomly divided into 5 groups (n=6/group): Control group; TMZ group; TMZ+IFN group; TMZ+LEV group; TMZ+LEV+IFN group. Anti-tumor efficacy of five regimens for tumor-bearing mice was tested after treatment with TMZ (50 mg/kg, i.p.), IFN (2×105 IU, s.c.), LEV (150 mg/kg, i.p.), while TMZ dose were reduced to 12.5 mg/kg for U251 tumors. All drugs are given once a day for five consecutive days. After therapy, the size of tumor was measured every day until the control tumors reached 2000 mm3. Mice bearing U138 tumors were sacrificed at 40 days after therapy, and mice bearing U251 tumors were killed at 26 days after therapy. RESULTS We identified that both U138 and U251 tumor growth among TMZ group, TMZ+IFN group, TMZ+LEV group and TMZ+LEV+IFN group were significantly inhibited (P<0.05), compared with the control group. Tumor weight of all treating group was lower than that of the control group (P<0.05). The tumor weight of TMZ+LEV+IFN group was the lowest and significantly lower than that of TMZ+LEV group and TMZ group (P<0.05, respectively). No significant difference was found between TMZ+LEV+IFN group and TMZ+IFN group in U251 subcutaneous xenograft tumors, although the tumor weight was lower in TMZ+LEV+IFN group (P>0.05). In the treatment of mice bearing U138 glioma, TMZ+LEV+IFN regimen was significantly superior to TMZ+IFN regimen. CONCLUSION Our data demonstrate that both IFN and LEV can sensitize TMZ effect on glioma. TMZ-LEV-IFN cocktail appears the best regimen.


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