Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury

To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTSHistological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSIONDMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.

The Electrocatalytic Activity of Bare Pyrolytic Graphite and Single Wall Carbon Nanotube Modified Glassy Carbon Sensors Is Same for the Quantification of Bisoprolol Fumarate

A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electrochemical properties are investigated exercising the cyclic voltammetry and square wave voltammetry (SWV). Enhanced peak current associated with bisoprolol fumarate oxidation at EPPGE is due to its better electron transfer property. Quantification of bisoprolol fumarate was carried out at pH 7.2 at both the pyrolytic graphite electrodes. Well-defined peak has been observed at ~ 792 and 954 mV at EPPGE and BPPGE respectively for bisoprolol fumarate oxidation. The detection limit is found to be 2.8 × 10–7 M and 7.3 × 10–7 M for EPPGE and BPPGE respectively. A comparison of common quantification parameters for bisoprolol at carbon nanotube modified glassy carbon electrode and bare BPPGE and EPPGE has been made and it is observed that carbon naotube modified glassy carbon exhibits sensitivity and detection limit close to that observed at bare basal plane pyrolytic graphite electrode. The method developed is applicable for determination of bisoprolol fumarate in pharmaceutical preparations and real samples.

Effect of dimethyl fumarate on rats with chronic pancreatitis

Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats were given the intraperitoneal injection of L-arginine for 5times(250 mg/100 kg,twice per time,each interval of 1 h) for building of CP model.Rats were divided into control group,CP group,DMF group and CP+DMF group.Rats in CP+DMF group were given the oral intragastric administration of DMF(25 mg/kg),while rats in control group and CP group were given the equal volume of normal saline.The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed(IPGTT,2 g/kg).The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets.Meanwhile,the histology of non-endocrine tissues and levels of myeloperoxidase(MPO) and malondialdchyde(MDA) were detected.Results:Compared with control group,the weight of rats in CP group was significantly reduced at week 2,4 and 6;the blood glucose significantly increased,AUC increased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration increased,levels of MDA and MPO increased,the islet equivalent and islet activity decreased at 0.30,60,120 and 180 min.Compared with CP group,the weight of rats in CP+DMF group significantly increased at week 2,4 and 6;the blood glucose significantly decreased.AUC decreased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration decreased,levels of MDA and MPO decreased,the islet equivalent and islet activity increased at 0,30.60,120 and 180 min.Conclusions:DMF treatment can improve CP induced by L-argininc and islet function in rats.

Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

Metabolic rewiring underlies the effector functions of macrophages1-3,but the mechanisms involved remain incompletely defined.Here,using unbiased metabolomics and stable isotope-assisted tracing,we show that an inflammatory aspartate argininosuccinate shunt is induced following lipopolysaccharide stimulation.The shunt,supported by increased argininosuccinate synthase(ASS1)expression,also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination.Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase(FH)further increases intracellular fumarate levels.

Determination of Bisoprolol Fumarate by Fluorescence Quenching Method

[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcitation=277 nm andλemission=596 nm,with the increase of CCu2+,the fluorescence signal intensity of bisoprolol fumarate weakened,and the difference between the fluorescence intensity of bisoprolol fumarate itself and the fluorescence intensity of the test solution after the quencher Cu2+was added(ΔF)and Cbisoprolol fumarate showed a good linear relationship.[Results]In the range of 15.39-76.93μg/mL,ΔF=146.7 Cbisoprolol fumarate+482.1,r=0.9988,and the detection limit is 0.1391μg/mL.[Conclusions]The fluorescence quenching method has been applied to the determination of actual samples with a recovery rate of 99.9%and an RSD of 2.7%.The results are satisfactory.

Aqueous Diels-Alder Reactions of Cyclopentadicnc with Symmetric Diester of Fumarate or Maleate

Symmetric, diesters of cis- or trans- bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylate were prepared by aqueous Diels-Alder reaction of cyclopentadiene with symmetric diester of fumarate or maleate.

Effects of Ferrous Fumarate on Growth Performance,Blood Biochemical Parameters and Trace Elements of Oncorhynchus mykiss

[ Objective] The study aimed to discuss the effects of ferrous fumarate on growth performance, blood biochemical parameters and content of trace element of Oncorhynchus mykiss. [ Method ] Juvenile rainbow trout with an initial weight of （89.2 ±0.2） g were fed with the basal fodder supplemented with different levels of ferrous fumarate （0, 20, 40, 80,160 and 480 mg/kg iron） for 60 d, and the six groups were named DO, D20, D40, D80, D160 and D480, wherein DO was as the control group, actually containing 62.60, 79.50, 99.60, 139.30, 215.20 and 538.40 mg/kg iron respectively. [ Result] The growth performance of juvenile rainbow trout was not affected by different dietary iron levels obviously （ P 〉 0.05）. With the increase of dietary iron level, hemoglobin （Hb） content and number of red blood cells（RBC） rose firstly and then leveled off. No significance was found in hematocrit （Hct） among the six groups （P 〉0.05）. Iron content in the whole body, vertebrae and muscle increased significantly with the improvement of dietary iron level（ P 〈0.05）, and iron concentration in the liver increased firstly and then leveled off in groups from D40 to D480. No significant difference in zinc content of the whole body was found among the six groups （ P〉0.05）, while zinc content in the vertebrae and muscle in control group was significantly higher than that of other groups （ P〈0.05）, and zinc concentration in the liver in groups DO and 1320 was significantly higher than that of other groups （ P 〈0.05）. Copper content in the whole body increased significantly with the increase of dietary iron level （P 〈 0.05 ）, while no significant difference was observed in the vertebrae （ P 〉0.05）, and copper concentration in the muscle in control group was significantly lower than that of other groups （ P 〈0.05）. Serum lysozyme （LZM） activity of group DO was significantly lower than that of other groups （ P 〈 0.05） except for group D480 （ P 〉 0.05）. Catalase （CAT） activity of serum enhanced significantly （ P 〈 0.05） from DO to EH0 and then decreased obviously （P 〈0.05）. [ Conclusion] Based on hemoglobin and iron content in the liver, the broken-line model analysis showed that the dietary iron level provided by ferrous fumarate for juvenile rainbow trout was estimated to be 99.8 and 100.4 mg/kg respectively in the experiment.

Protective effect and mechanism of clemastine fumarate on acute lung injury in mice with intestinal ischemia-reperfusion

Objective:To evaluate the protective effect and mechanism of clemastine fumarate(CLE)on acute lung injury(ALI)in intestinal ischemia-reperfusion(I/R)mice.Methods:Twenty-four SPF Balb/c mice were randomly divided into sham operation group(sham group),ischemia-reperfusion group(I/R group),and clemastine fumarate pretreatment group(I/R+C group).In the I/R group,an intestinal ischemia-reperfusion model was established(ischemia for 40 minutes,reperfusion for 2 hours).In the I/R+C group,CLE 5 mg/kg was intraperitoneally injected before the operation.Lung tissue morphology was observed and scored by HE staining;and the ratios of wet weight to dry weight(W/D)were recorded.the levels of MDA,SOD,GSH-px,NF-κB and TNF-αin lung tissue of each group were determined by ELISA;Western blot method was used to determine the expression of TLR4 protein in lung tissue.Results:Compared with the Sham group,the I/R group had significantly higher lung tissue injury score and wet/dry ratio(P<0.05),increased lung tissue MDA level(P<0.05),decreased SOD and GSH-px levels(P<0.05),and increased NF-κB and TNF-αlevels,the expression of TLR4 protein in lung tissue increased(P<0.05);compared with the I/R group,the lung tissue injury score and wet/dry ratio of the I/R+C group decreased(P<0.05),the level of MDA in lung tissue decreased(P<0.05),the levels of SOD and GSH-px increased(P<0.05),and the levels of NF-κB and TNF-毩decreased(P<0.05),the expression of TLR4 protein in lung tissue decreased(P<0.05).Conclusion:Clemastine fumarate can alleviate acute lung injury after intestinal ischemia-reperfusion in mice,and the mechanism may be related to the inhibition of oxidative stress and inflammatory response in lung tissue.

欧洲药品评审局批准Aclidinium Bromide—Formoterol Fumarate Dihydrate复方制剂上市

欧洲药品评审局（EMA）于2014年11月19Et批准艾美罗（Almirall）公司的Aclidinium Bromide-Formoterol Fumarate Dihydrate（参考译名：阿地溴铵一富马酸福莫特罗，商品名：Duaklir Genuair、Brimica Genuair）粉雾剂上市，作为成人慢性阻塞性肺疾病（COPD）的维持治疗。

Treatment of Chronic Hepatitis B with Tenofovir Disoproxil Fumarate in Ivory Coast

Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and methods: A descriptive single-center retrospective study, on chronic viral hepatitis B mono-infected, followed in the hepatogastroenterology department of the University Hospital of Yopougon and treated with tenofovir from February 2012 to February 2015. The studied parameters were demographic, clinical, biochemical, serological, virological, abdominal ultrasound. Liver fibrosis was assessed either by liver biopsy or non-invasive tests. Results: 110 patients were treated with tenofovir disoproxil fumarate with a mean age of 40.4 years and a male predominance. Clinical examination revealed jaundice in 9% of cases, hepatomegaly in 7.3% of cases, splenomegaly in 9.1% of cases and ascites in 15.5% of cases. The AST averaged 77.3 IU/l, the ALT 76.8 IU/l, prothrombin rate at 76.6% , albumin level at 32.3 g/l, total bilirubin at 29.9 g/l, alpha fetoprotein rate at 15.3 ng/ml. HBe antigen was negative in 76.2% of cases. The average rate of DNA at baseline was 7.4 log10 IU/l. 27.5% was cirrhotic. The average time of starting treatment was 23.7 months. Conclusion: TDF is the first-line treatment for chronic hepatitis B in our country, because it is a well-tolerated, potent therapy with a high threshold for resistance development. Our study population had an average age of 40.4 years. Virological profile was dominated by HBe antigen negative patients and high viral load of HVB DNA. One third of patients were at the stage of cirrhosis. This treatment must be delivered free of charge in all the country hospitals, which is going to improve significantly the natural evolution of the disease and to decrease the incidence of the HCC.

Pre-Formulation Development of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF) 300 mg Fixed Dose Combination Tablets

Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm-1 (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.

Progress in the Study of Vonoprazan Fumarate vs. Proton Pump Inhibitors in the Treatment of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.

Design and preparation of a crosslinkable,oil-resistant,and bio-based elastomer from fumarate

Poly(diethyl fumarate-co-methoxyethyl acrylate-co-vinyl chloroacetate)(PDEFMV),a novel bio-based elastomer with a saturated structure,was synthesized via redox emulsion polymerization.The glass-transition temperatures of PDEFMV,adjusted through the variation of the diethyl fumarate-to-methoxyethyl acrylate feeding ratio,ranged from-36.1 to-14.8 ℃.The number-average molecular weights of PDEFMV ranged from 384,000 to 46,000 g/mol.In designing the molecular structure,vinyl chloroacetate was used to provide active sites for subsequent vulcanization and crosslinking.The active chlorine groups within the PDEFMV chain reacted with the crosslinking agent trithiocyanuric acid under high temperature and pressure to form a nonsulfur crosslinked three-dimensional network structure.To achieve the desired properties,carbon black(CB,N330) was incorporated to reinforce PDEFMV,leading to the formation of PDEFMV/CB composites.A comprehensive study was conducted on the high-temperature oil resistance of PDEFMV/CB composites.Following immersion in IRM903 oil at temperatures of 150 and 200 ℃ for 72 h,the mass and volume changes in PDEFMV/CB were lower than those observed in commercially available acrylate rubber(AR)/CB,indicating that PDEFMV exhibited superior oil resistance.Furthermore,the aging characteristics and mechanisms of oil resistance in the PDEFMV/CB and AR/CB composites were investigated at different temperatures(150,200,and 250 ℃).The results provide insights into the operational temperature ranges suitable for PDEFMV/CB and offer valuable guidance for potential industrial applications.

Differences of Efficacy Between Tenofovir Alafenamide Fumarate and Tenofovir Disoproxil Fumarate in Pregnant Women With Different Hepatitis B Virus DNA Loads

Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumarate(TDF).However,there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads.This study retrospectively analyzed 96 hepatitis B e antigen(HBeAg)–positive pregnant women with HBV DNA levels of≥2×10^(5) IU/mL.Based on viral loads(HBV DNA levels),participants in the TAF and TDF groups were stratified into three subgroups,namely,the High-G(titer≥8 log_(10) IU/mL),Middle-G(7 log_(10) IU/mL≤titer<8 log_(10) IU/mL)and Low-G(titer<7 log_(10) IU/mL)subgroups.The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads,whereas secondary endpoints were hepatitis B surface antigen(HBsAg)positivity in infants at 7 to 12 months and the safety profile for mothers and children.Compared with baseline levels,median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log_(10) IU/mL in the TAF andTDF groups(P=0.04)predelivery,respectively.In the High-G subgroup,the titers were significantly lower in the TAF group(P=0.045).A higher proportion of patients experienced a virus decline of≥4 log_(10) IU/mL in the TAF group compared with the TDF group,with rates of 78.26% versus 58%(P=0.034),respectively.Moreover,the median serum phosphate levels significantly decreased frombaseline to predelivery in the TDF group(P=0.04).Finally,infants in both cohorts tested negative for HBsAg at 7–12 months after delivery.Overall,our findings indicate that TAF can be considered the preferred option for the treatment of HBeAgpositive pregnant women with HBV DNA levels of≥8 log_(10) IU/mL.

HBsAg kinetics after 7 years of therapy with tenofovir disoproxil fumarate in a cohort of naïve patients affected by chronic hepatitis B with different genotypes

Background:The role of different genotypes in nucleos(t)ide analogs(NAs)treatment is still debated.Previous studies conducted on special populations evidenced that the E genotype had the lower virological and serological response.This descriptive study aims to recognize the hepatitis B“s”antigen(HBsAg)decline during tenofovir disoproxil fumarate(TDF)treatment in a cohort of patient affected by chronic hepatitis B(CHB).Methods:We retrospectively included all patients with CHB treated with TDF between April 2007 and March 2012 with a duration of treatment of 7 years.Kinetics of HBsAg was determined as serological response in this cohort.We include 110 subjects;virological response was observed in all subjects with genotypes A,B,and D;in 17 patients with C genotype(94.4%)and 24 with E genotype(96%).HBeAg loss was observed in 2 patients with genotype A(50%),3 with B(100%),0 with C(0%),1 with D(20%),and 1 with E genotype(25%).Results:In multivariate analysis we observed as predictive factors of HBsAg decline the baseline level of HBsAg(OR=1.467;95%CI:1.221–5.113;p=0.017)and viral genotypes(OR=11.218;95%CI:5.441–41.138;p<0.001).Conclusion:This study confirmed higher HBsAg decline after 7 years of treatment in A and B genotypes,and lower in C,E,and D genotypes.However,no evidence is enough to choose a single NAs,but in special populations,as well as in genotype E,the use of TDF should be preferred to entecavir.

Monomethyl fumarate augments NK cell lysis of tumor cells through degranulation and the upregulation of NKp46 and CDIO7a

Dimethyl fumarate （DMF） is a new drug used to treat multiple sclerosis （MS） patients. Here, we examined the effects of DMF and the DMF metabolite monomethyl fumarate （MMF） on various activities of natural killer （NK） cells. We demonstrated that MMF augments the primary CD56^＋, but not CD56^-, NK cell lysis of K562 and RAJI tumor cells. MMF induced NKp46 expression on the surface of CD56^＋, but not CD56^-, NK cells after incubation for 24 h. This effect was closely correlated with the upregulation of CD107a expression on the surface of CD56＋ NK cells and the induction of Granzyme B release from these cells through this metabolite. An anti-NKp46 antibody inhibited the MMF-induced upregulation of CD107a and the lysis of tumor cells through CD56^＋ NK cells. Thus, these results are the first to show that MMF augments CD56^＋ NK cell lysis of tumor target cells, an effect mediated through NKp46. This novel effect suggests the use of MMF for therapeutic and/or preventive protocols in cancer.

Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord

The aim of this work was to study effects of ketotifen fumarate(KF)on prevention of tissue damage in testes of rats with experimental autoimmune orchitis(EAO)and on the contralateral testis in a model of prolonged testicular cord torsion(TCT).Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution(vehicle group).Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score.Mast cells(MC)were identified by histochemistry and quantified.In EAO model,KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group.KF also reduced the number of testicular MC compared to vehicle group.Similarly,in TCT model,multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium,seminiferous tubule atrophy,and interstitial edema.Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed.In contrast,sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features.A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals.In conclusion,we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models.The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.

Rapid Recovery in COVID-19 Patients with Chronic Hepatitis B Virus Infection Treated with Tenofovir Disoproxil Fumarate

The coronavirus disease 2019(COVID-19)pandemic continues worldwide.We report here two cases of chronic hepatitis B patients with acute respiratory syndrome coronavirus 2 infection treated with tenofovir disoproxil fumarate who demonstrated a favorable outcome.This report adds some evidence that concurrent HBV infection may not worsen COVID-19 infection and tenofovir disoproxil fumarate treatment may have partial positive effect on COVID-19 rapid recovery.