Blood Alkaline Phosphatase Research Articles

Fibrous dysplasia of thoracic and lumbar spine: A case report

IntroductionFibrous dysplasia (FD) is a rare genetic disease characterized by development of dysplastic bone tissue leading to pain, deformities and compressive complications. Spinal involvement is rare particularly for the polyostotic form. Case reportHerein, we present a case of 52-year-old man presented with isolated low back pain who received non-steroidal anti-inflammatory drugs (NSAIDs) with partial pain relief. On examination, the thoracic and lumbar spines were tender. Lumbar spine movements, attested by Shöber’s test and finger-to-floor test, were limited. There was no radicular pain and neurological examination was normal. The erythrocyte sedimentation rate was 20 mm/1st hour, C- reactive protein 2 mg/l and white blood cell count, serum calcium, phosphorus, alkaline phosphatase and parathormone were normal. Plain x-ray lumbar and thoracic spine and hips were normal. X-ray cervical spine and peripheral bone showed no lesions. Computed tomography (CT) and magnetic resonance imaging showed multiple osteolytic lesions with ground-glass opacity and sclerotic rims of thoracic and lumbar (L1 and L2) spine. Investigations to rule out malignancy or infections were negative. CT guided biopsy of a lumbar vertebra was performed and showed the presence of abnormal fibrous matrix surrounding an irregular shaped immature bone. The diagnosis of polyostotic FD of the spine was made. Zoledronic acid infusion was introduced and the patient felt better thereafter with no additional osteolytic lesions or new pain localization reported for 2 years on follow up. ConclusionThoracic and lumbar spine FD is a rare localization that should be considered in the differential diagnosis of back pain.

Machine learning approaches in predicting ambulatory same day discharge patients after total hip arthroplasty

BackgroundWith continuing financial and regulatory pressures, practice of ambulatory total hip arthroplasty is increasing. However, studies focusing on selection of optimal candidates are burdened by limitations related to traditional statistical...

Effects of zinc sulfate and coated zinc sulfate on lactation performance, nutrient digestion and rumen fermentation in Holstein dairy cows

This study was to evaluate impacts of zinc sulfate (ZS) and coated ZS (CZS) supplementation on milk performance, nutrient digestibility and rumen fermentation. Forty-five Holstein dairy cows were assigned in a randomized block design to one of five treatments: control, ZS supplementation (30 mg Zn/kg dry matter [DM] as ZS) or CZS supplementation (10, 20 and 30 mg Zn/kg DM as CZS for LCZS, MCZS and HCZS, respectively). The experiment lasted for 110 days with 20 days for adaptation and 90 days for data collection. When comparing Zn source at same supplemental level (30 mg Zn/kg DM), milk yield and total-tract digestibility of neutral detergent fibre (NDF) and acid detergent fibre (ADF) tended to be higher and ruminal activities of xylanase, cellobiase, pectinase and protease and serum alkaline phosphatase (ALP) were higher for HCZS than for ZS. Increasing CZS addition linearly increased DM intake and yields of milk, milk fat and milk protein but did not affect milk lactose yield, milk composition content and feed efficiency. Digestibility of DM, organic matter, crude protein, NDF and ADF, ruminal total volatile fatty acids content and acetate to propionate ratio linearly increased but ammonia N content linearly decreased with increasing CZS addition. Quadratic responses were observed for proportions of acetate and propionate. Activities of cellulase and protease and populations of total bacteria, fungi, protozoa, dominant cellulolytic and amylolytic (proteolytic) bacteria responded linearly and positively with increasing CZS addition. Increasing CZS addition linearly increased liver Zn and blood total protein, albumin, ALP and Zn. Results indicated that CZS could be used as a Zn supplement in cows, and supplementing 20 or 30 mg/kg DM of Zn from CZS stimulated performance, nutrients digestion and ruminal fermentation and improved Zn status in cows fed diets containing 31.2 mg Zn/kg DM.

Growth performance, ascites sensitivity, and ileal microbiota as affected by licorice essential oil in broiler chicken diets

This experiment was conducted to evaluate the effect of licorice (Glycyrrhiza glabra) essential oil (LEO) as an alternative to antibiotic growth promoter on growth performance, ileal microbial population, blood biochemical traits, and ascites sensitivity in broiler chickens. A total of 625 one-day-old broiler chickens were assigned to 5 dietary treatments, including control(un-supplemented basal diet), antibiotic (basal diet + 150 mg avilamycin/kg), probiotic (basal diet + 100 mg probiotic/kg), basal diet + 200 mg LEO/kg, and basal diet + 400 mg LEO/kg, in a completely randomized design, with 5 replicates of 25 broiler chickens per pen. Dietary inclusion of 200 mg LEO/kg increased feed intake compared to control and 400 mg LEO/kg treatments (P < 0.05). Broiler chickens fed the diet containing 200 mg LEO/kg showed greater weight gain and better feed conversion ratio (P < 0.05) compared to diets containing 400 mg LEO/kg. No differences were observed in feed intake and weight gain among diets containing 200 mg LEO/kg, antibiotic, probiotic, or control treatment. No differences in blood lipids, Alkaline phosphatase, and albumin were observed among all the treatments. The concentrations of total protein and globulin in serum of broiler chickens fed control diet were greater than broiler chickens that received antibiotic, probiotic, or 400 mg LEO/kg (P < 0.05). Diet containing 200 mg LEO/kg caused the greatest serum concentration of T3 or T4 (P < 0.05). The T4/T3 ratio in broiler chickens fed the diet containing 400 mg LEO/kg was greater than those fed the antibiotic or control diets (P < 0.05). Also, broiler chickens fed 400 mg LEO/kg diet had lower right ventricle /total ventricles ratio (RV/TV) than those fed the control, antibiotic, or 200 mg LEO/kg diets (P < 0.05). The ileal population of Escherichia coli in broiler chickens fed diets containing 200 or 400 mg LEO/kg was lower than those fed the control diet (P < 0.05). The result indicates that LEO can improve thyroid hormones and reduce the population of some potential pathogenic bacteria in broiler chickens' gut, resulting in better growth performance. Therefore, LEO can be recommended as much as 200 mg/kg of diet as an alternative to antibiotics in promoting the growth performance of broiler chickens.

Multi-Probiotic Lactobacillus Supplementation Improves Liver Function and Reduces Cholesterol Levels in Jeju Native Pigs.

Simple SummaryProbiotics are used in the food industry as feed additives to maintain the balance of animal gut microbiota. They are also considered to have potential therapeutic effects against liver diseases. This study showed that dietary Lactobacillus supplementation improved liver function and reduced cholesterol levels in Jeju native pigs, with Toll-like receptors (TLR) signaling as the primary response in the gut against Lactobacillus and TNF-α/IFN-γ as the central mediator cytokines in the gut and liver tissues. Lactobacillus supplementation may be applied to treat metabolic disorders of the liver, especially cholesterol-related disorders, in farm animals.We evaluated the dietary effects of multiple probiotics in Jeju native pigs, using basal diet and multi-probiotic Lactobacillus (basal diet with 1% multi-probiotics) treatments (n = 9 each) for 3 months. We analyzed growth performance, feed efficiency, backfat thickness, blood parameters, hematological profiles, adipokines, and immune-related cytokines in pig tissues. Average daily gain, feed intake, feed efficiency, backfat thickness, and body weight were not significantly different between both groups. In Lactobacillus group, total protein (p < 0.08) and bilirubin (p < 0.03) concentrations increased; blood urea nitrogen (p < 0.08), alkaline phosphatase (p < 0.08), and gamma-glutamyltransferase (p < 0.08) activities decreased. Lactobacillus group showed decreased adiponectin (p < 0.05), chemerin (p < 0.05), and visfatin expression in adipose tissues, and increased TLR4 (p < 0.05), MYD88 (p < 0.05), TNF-α (p < 0.001), and IFN-γ (p < 0.001) expression in the liver. Additionally, NOD1 (p < 0.05), NOD2 (p < 0.01), and MYD88 (p < 0.05) mRNA levels in proximal colon tissue upregulated significantly. Colon, longissimus dorsi muscle, fat tissue, and liver histological analyses revealed no significant differences between the groups. Conclusively, Lactobacillus supplementation improved liver function and reduced cholesterol levels. Its application may treat metabolic liver disorders, especially cholesterol-related disorders.

Blood alkaline phosphatase predicts prognosis of patients with advanced HER2-negative gastric cancer receiving immunotherapy.

BackgroundImmune checkpoint blockade is effective against many cancer types, but few patients achieve a complete response (OR). Therefore, effective prognostic biomarkers are needed for metastatic gastric cancer (GC) patients after immune treatment. The present study assessed the value of hematological parameters as markers of the effectiveness of immune checkpoint blockade among metastatic GC patients.MethodsThis retrospective study included patients with metastatic GC who underwent multiline chemotherapy including at least two courses of immunotherapy between September 2018 and December 2020. Patient and tumor characteristics were tested for prognostic significance by analysis of variance or chi-square test. Kaplan-Meier and Cox analyses were performed to identify factors associated with progression-free survival (PFS).ResultsSixty-one GC patients (mean age 55.61±11.97 years, range 23–80 years, 24 females, and 37 males) were included, and 27, 9 and 25 cases had organ only, peritoneum only, and simultaneous organ and peritoneum metastasis, respectively. Gastrectomy was performed in 24 cases, and there was no operative treatment in the other 37 cases, while all patients received two or more lines of chemotherapy. After immune treatment, 13 patients achieved a partial response (PR), 16 stable disease (SD), and 32 progressive disease (PD). The median PFS was 4.93±3.47 months. An alkaline phosphatase (ALP) level >225 U/L, a lactate dehydrogenase level (LDH) >299 U/L, and a body mass index (BMI) >24 kg/m2 were associated with a short PFS (P=0.01, P=0.008, and P=0.039, respectively). A Cox multivariate proportional hazard model indicated that higher ALP level was a significant prognostic indicator for adverse PFS.ConclusionsOur data show an ALP cutoff of 225 U/L offered good prognostic sensitivity for HER2-negative metastatic GC. ALP measurement represents a convenient, cost-effective, and relatively sensitive screening tool, and prospective studies involving its evaluation in addition to other biomarkers in metastatic GC patients are indicated.

A dual-signal sensing platform based on nanosheet materials for ratiometric fluorescence and colorimetric detection of enzyme activities in human blood

A dual-signal sensing platform comprising g-C3N4/MnO2 nanosheet composite and a routine chromogenic reagent o-phenylenediamine (OPD) was constructed for activity evaluation of several enzymes including Alkaline phosphatase (ALP), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) in human blood. MnO2 nanosheets was employed as a catalyst for oxidizing OPD to fluorescent 2,3-diaminophenazine (oxOPD), while g-C3N4 nanosheets served as a fluorescent indicator. MnO2 nanosheets also exhibited inner filter effect (IFE) on the fluorescence of g-C3N4 nanosheets due to the overlap of their respective absorption band and fluorescence emission band. Similarly, oxOPD would quench the fluorescence of g-C3N4 nanosheets via photoinduced electron transfer (PET) process. By using L-ascorbic acid-2-phosphate (AAP) and acetylthiocholine iodide (ATCh) as substrates, products of target enzyme-catalyzed hydrolysis reactions would reduce MnO2 nanosheets to Mn2+ cations, resulting in the inhibition of OPD oxidation and the fluorescence recovery of g-C3N4 nanosheets. Based on these reactions and effects, activities of target enzymes were indicated by the intensity ratio of fluorescence emitted from g-C3N4 nanosheets and oxOPD (F440/F560), as well as by the absorbance decrease of oxOPD at 420 nm (ΔA420). Limits of detection (LODs) obtained by the sensing platform for ALP, AChE, and BChE were respectively 0.28 U L-1, 0.19 U L-1, and 0.15 U L-1 for ratiometric fluorescence mode, and 1.3 U L-1, 1.0 U L-1 and 0.9 U L-1 for colorimetric mode. This dual-signal sensing platform can be extended for testing other enzymes after applying appropriate substrates for target enzyme-catalyzed hydrolysis reactions and demonstrates good potential for clinical diagnosis.

The laboratory and clinical factors associated with mortality in COVID-19 patients

Background: In December 2019, the Chinese government declared the prevalence of a new epidemic belonging to the coronavirus family;later, this epidemic was called COVID-19. Objectives: To determine the clinical and laboratory factors involved in the mortality of hospitalized COVID-19 patients. Methods: This descriptive-analytic study was performed in Kowsar Hospital of Semnan, Iran, using medical files of 107 patients hospitalized during February-April 2020 with COVID-19 diagnosis with the presence of chest CT findings. The patients’ demographic information, vital signs, clinical symptoms, lab test results, the prescribed medicines during hospitalization, past medical history, and outcomes were analyzed. The relationship between each of the explanatory variables with death outcome was examined using univariate and multivariate logistic regression models, reporting crude and adjusted odds ratios (OR & Adj. OR). Results: The mean age of the patients was 63.36 ± 16.43 years, 67 (62.6%) patients were male, and 85 (79.4%) patients were discharged. Low level of consciousness (Glasgow coma scale < 14) (discharged: 8.2% vs. expired: 40.2%, Adj. OR [95% confidence interval] = 17.9 [3.1, 102.7]), higher body temperature (37.1°C vs. 37.74°C, 3.62 [1.55, 8.43]), and higher blood alkaline phosphatase (177.6 vs. 247.6, 1.01 [1.00, 1.01]) at the time of hospitalization were associated with increased mortality. Also, having the symptom of fatigue or weakness at the time of hospitalization (61.2 vs. 36.4%, 0.06 [0.01, 0.46]), higher red blood cells count (4.67 vs. 4.15, 0.21 [0.08, .55]), and higher blood oxygen saturation levels (89 vs. 82%, 0.92 [0.85, 0.99]) were associated with a lower risk of mortality. Conclusions: Decreased level of consciousness at the time of admission was shown to be a critical and independent predictor of mortality. Several factors are associated with death in patients with COVID-19, which due to the complexity of the relationship between each of them, it is not practical and plausible to make a definite prediction of patients’ prognosis only by noting few factors without considering all the clinical symptoms and laboratory findings. The results of individual studies like ours should be interpreted alongside the results of previous and future clinical studies and not alone. © 2021, Semnan University of Medical Sciences. All rights reserved.

Serum Lipid, Amino Acid and Acylcarnitine Profiles of Obese Cats Supplemented with Dietary Choline and Fed to Maintenance Energy Requirements.

Simple SummaryResearch has estimated that the majority of domestic cats are overweight or obese. Current weight-loss plans tend to have disappointing outcomes and are not without risk. During periods of severe energy restriction, obesity predisposes cats to developing fatty liver. Choline has been linked to fat metabolism in other animals but has not been studied in cats. Twelve obese cats were split into two groups and were fed a control diet (n = 6; 4587 mg choline/kg dry matter) or a high choline diet (n = 6; 18,957 mg choline/kg DM) for 5 weeks. Cats were fed to maintain body weight. Choline increased serum cholesterol, triacylglycerides, lipoproteins, and plasma methionine. It also decreased serum blood urea nitrogen and alkaline phosphatase as well as the ratio of plasma acylcarnitine to free carnitine. The results suggest that choline supplementation may increase fat transport out of the liver and help maintain liver health in obese cats. Choline supplementation may prove useful for safe weight loss in obese cats by minimizing the risks of fatty liver.Obesity is a health concern for domestic cats. Obesity and severe energy restriction predispose cats to feline hepatic lipidosis. As choline is linked to lipid metabolism, we hypothesized that dietary choline supplementation would assist in reducing hepatic fat through increased lipoprotein transport and fatty acid oxidation. Twelve obese cats (body condition score [BCS] ≥ 8/9) were split into two groups. Cats were fed a control (n = 6; 4587 mg choline/kg dry matter [DM]) or a high choline diet (n = 6; 18,957 mg choline/kg DM) for 5 weeks, for adult maintenance. On days 0 and 35, fasted blood was collected, and the body composition was assessed. Serum lipoprotein and biochemistry profiles, plasma amino acids and plasma acylcarnitines were analyzed. The body weight, BCS and body composition were unaffected (p > 0.05). Choline increased the serum cholesterol, triacylglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and plasma methionine (p < 0.05) and decreased the serum blood urea nitrogen and alkaline phosphatase (p < 0.05). Choline also reduced the plasma acylcarnitine to free carnitine ratio (p = 0.006). Choline may assist in eliminating hepatic fat through increased fat mobilization and enhanced methionine recycling.

Evaluation of lipolysis and toxicological parameters of low-level laser therapy at different wavelengths and doses in the abdominal subcutaneous tissue.

Investigate the effects of low-level lasers therapy (LLLT) aiming abdominal lipolysis. Female Wistar rats received applications of LLLT directly in the abdominal skin twice a week (5weeks). Except the control group (n = 5), animals received treatments with red wavelength 660nm being (I) R3.3 group (n = 5): 3.3J/cm2, and (II) R5 group (n = 5): 5J/cm2, or infrared wavelength 808nm being (III) IR3.3 group (n = 5): 3.3J/cm2, and (IV) IR5 group (n = 5): 5J/cm2. Abdominal subcutaneous and liver tissues were evaluated histologically. Levels of thiobarbituric acid reactive substances (TBARS) and catalase (CAT) activity were analyzed in liver tissue. In the peripheral blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, and total cholesterol were investigated. Micronucleus assay was performed in the bone marrow. Except for the IR3.3 group, all treated groups reduced the body weight (p < 0.001). The R5 group reduced the abdominal subcutaneous tissue weight and thickness (p < 0.05), even though all treated groups reduced the number of adipocytes and its size (p < 0.001). No histological changes in the liver. There were no alterations in the triglycerides and LDL levels. The IR5 group increased the total cholesterol levels and decreased the HDL, ALT (both p < 0.05), and AST levels (p < 0.001). The group IR3.3 showed higher levels of ALP (p < 0.01). The R3.3 group increased the TBARS and CAT activity (p < 0.05). No mutagenic effects were found. The red laser treatment at 5J/cm2 led to lipolysis and did not alter the liver's parameters.

Ameliorative effect of the dietary Egyptian leek ( Allium ampeloprasum L. var. kurrat ) on zinc toxicity of the African catfish Clarias gariepinus (Burchell, 1822)

There is scant knowledge available concerning the protective role of the Allium ampeloprasum L. on African catfish (Clarias gariepinus) that is chronically exposed to zinc (Zn). Six fish groups were used: three were fed diets supplemented with leek extract (LEE 0%, 2% and 4%); and the three other groups received LEE and were exposed to a sublethal dose of zinc sulphate (7.8 mg L−1). After 45 days, fish exposed only to Zn exhibited the highest values of weight gain, specific growth rate, white blood cell count, alanine aminotransferase, alkaline phosphatase, proteins, albumin, globulin, glucose, creatinine and total antioxidant concentration significantly. Fish exposed to Zn-only also revealed insignificant changes in the condition coefficient, hepatosomatic index, gonadosomatic index and almost all haematological parameters. Moreover, exposure to only Zn resulted in a significant decrease in aspartate aminotransferase (AST). Feeding on LEE 2% increased growth, whereas LEE 4% had an insignificant effect on growth; both LEE doses caused insignificant changes in haematological and biochemical parameters. Feeding on LEE while being exposed to Zn showed a reduction in some elevated biochemical parameters compared with the Zn-only-exposed group, with LEE 2% displaying a greater protective role than LEE 4%. Histopathological investigations revealed many changes in the livers of fish fed with LEE, while it has more degenerative and necrotic changes with exposure to Zn. So, leek extract could be used at the lower dose for African catfish as a feed supplement to improve fish growth and alleviate the possible undesired effects of chronic exposure to Zn.

Effects of Ovariectomy-Induced Estrogen Deficit on Rat Behaviour, Lipid Metabolism, Inflammation, Bone Mineral Density, and Turnover

The objective of the present study was to make a complex evaluation of behaviour, lipid metabolism, inflammation, and bone turnover in an ovariectomized rat model used to simulate postmenopausal clinical findings. Female Wistar rats were divided into 2 groups of 16 animals each: sham operated (SO) animals and ovariectomized (OVX) animals. Three months after the operation, a battery of behavioural tests was performed including an open field test (OFT), elevated pus-maze test (EPM), the social interaction test (SIT), the forced swim test (FST), and a hot plate test (HPT). At termination of experiment, weight gain and fat deposits (total and retroperitoneal) were measured. Serum concentrations of blood lipids were determined. Tumor necrosis factor alpha (TNF-alpha) and alkaline phosphatase (ALP) serum concentrations were used for evaluation of the inflammation and bone turnover, respectively. Femur bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry. OVX rats did not demonstrate any significant behavioural changes in OFT and EPM tests but showed a decreased interaction time in SIT and an increased immobility time in FST test which indicated anxiety and depression. The OVX rats had a significantly lower pain sensitivity threshold. They had greater weight gain, increased total and retroperitoneal fat deposits, as well as elevated total fat/body weight and retroperitoneal fat/body weight ratios. Blood cholesterol, ALP and TNF-alpha of the OVX group were also significantly higher. Femur BMD of OVX rats was slightly but not significantly reduced. Estrogen deficiency in OVX rats caused depression, anxiety, hyperalgesia, obesity, dyslipidemia, and inflammation before the reduction in bone mineral density was prominent.

Encouraging Early Results from the First in-Human Clinical Trial of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory B-Cell Lineage Non-Hodgkin Lymphoma

Introduction: CD19 is expressed on the cell surface of many types of non-Hodgkin lymphoma (NHL), including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) comprising a humanized antibody (Ab) directed against human CD19 conjugated to a pyrrolobenzodiazepine (PBD) dimer toxin. Loncastuximab tesirine (Lonca-T) has demonstrated potent anti-tumor activity against CD19-expressing B-cell malignancies in preclinical models. Interim results of the first-in-human clinical study of Lonca-T in the difficult-to-treat relapsed/refractory (R/R) NHL setting are reported here.Methods: Patients (pts; ≥18 years of age) with R/R B-cell lineage NHL who have failed or are intolerant to established therapies, or have no other treatment options available, are being enrolled in this Phase 1, multicenter, open-label, two-part study. The primary objectives for Part 1 (dose escalation) are to evaluate the safety and tolerability of Lonca-T, and to determine the maximum tolerated dose (MTD) and the recommended dose(s) to use in Part 2 (dose expansion). The primary objective for Part 2 is to evaluate the safety and tolerability of the dose(s) determined in Part 1. Efficacy (measured by overall response rate [ORR], duration of response [DoR], progression-free survival [PFS] and overall survival), pharmacokinetics, pharmacodynamics, and other exploratory endpoints are also being assessed in both parts of the study. Pts receive 1-hour intravenous infusions of Lonca-T every 3 weeks (1 cycle) according to a 3+3 dose-escalation study design. No intra-patient dose escalation is allowed.Results: As of July 5, 2017, 80 pts (55 male, 25 female; median age: 65.5 years [range 24-85]; median number of previous therapies: 3 [range 1-10]) have been recruited. Diagnoses were DLBCL (n=56), mantle cell lymphoma (MCL; n=9), FL (n=6), marginal zone B-cell lymphoma (n=3), chronic lymphocytic leukemia (n=2) and other (n=4). Pts have received doses of Lonca-T ranging from 15 to 200 µg/kg (median cycles: 2 [range 1-16]). Treatment-emergent adverse events (TEAEs) were reported in 76 (95.0%) pts, and grade ≥3 TEAEs in 46 (57.5%) pts. The most common non-hematological all-grade TEAEs were fatigue (35 [43.8%] pts), peripheral edema (21 [26.3%] pts) and nausea (20 [25.0%] pts), and grade ≥3 TEAEs were increased gamma-glutamyltransferase (7 [8.8%] pts) dyspnea (4 [5.0%] pts) and fatigue (4 [5.0%] pts). Hematological abnormalities included decreased hemoglobin (74/77 [96.1%] and 9/77 [11.7%] pts with all-grade and grade ≥3 TEAEs, respectively), decreased neutrophil count (42/69 [60.9%] and 29/69 [42.0%] pts, respectively) and decreased platelet count (55/77 [71.4%] and 21/77 [27.3%] pts, respectively). TEAEs in 8 (10.0%) pts led to treatment withdrawal (increased gamma-glutamyltransferase [n=4]; increased blood alkaline phosphatase [n=1]; periorbital edema [n=1]; fatigue [n=1]; abdominal pain [n=1]; thrombocytopenia [n=1]). A dose-limiting toxicity (DLT) was reported in 1 pt (worsening of thrombocytopenia at 200 µg/kg) and the MTD has not yet been reached. Table 1 shows the best overall response by dose. At doses ≥120 µg/kg, 16/47 (34.0%) and 12/47 (25.5%) evaluable pts achieved a complete response (CR) or partial response (PR), respectively (ORR: 28/47 [59.6%]). ORR for pts with DLBCL was 20/35 (57.1%), with a CR rate of 34.3% (12/35). Figure 1 depicts the waterfall plot. Pharmacokinetic measures for total- and PBD-conjugated Ab exposures were comparable, were proportional to dose, and were associated with modest accumulation by Cycle 2. Measures for unconjugated PBD were predominantly below quantification levels for all doses and time points. Associations of exposure to safety and efficacy are reported in a companion abstract (O O'Connor et al.).Conclusions: In this Phase 1 study, Lonca-T has demonstrated encouraging single-agent anti-tumor activity and manageable toxicity in pts with R/R B-cell lineage NHL. One DLT has been reported and the MTD has not yet been reached. Evaluation in specific NHL subtypes is now warranted, and a dose expansion in pts with DLBCL is planned initially. Updated safety, tolerability, and efficacy results will be presented at the meeting.Study sponsored by ADC Therapeutics. http://clinicaltrials.gov/show/NCT02669017 [Display omitted] DisclosuresKahl:ADC Therapeutics: Research Funding; Celgene: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; Genentech: Consultancy. Hamadani:Takeda, Otsuka, MedImmune, Merck, ADC Therapeutics: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Celgene, Cellerant, Jansen, MedImmune: Consultancy. Caimi:Seattle Genetics: Equity Ownership; Incyte: Equity Ownership; Abbvie: Equity Ownership; Celgene: Speakers Bureau. Carlo-Stella:ADC Therapeutics: Research Funding. Reid:ADC Therapeutics, Millennium: Research Funding. Feingold:ADC Therapeutics: Employment, Other: Potential equity interest. Ardeshna:ADC Therapeutics: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Conference Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Conference Expenses, Research Funding. Radford:Takeda: Research Funding, Speakers Bureau; Seattle Genetics: Speakers Bureau; Novartis: Speakers Bureau; GlaxoSmithKline: Equity Ownership; AztraZeneca: Equity Ownership; ADC Therapeutics: Research Funding. Solh:Celgene: Speakers Bureau; Amgen: Speakers Bureau; ADC Therapeutics: Research Funding. Chung:ADC Therapeutics: Research Funding. Heffner:ADC Therapeutics: Research Funding. He:ADC Therapeutics: Employment, Other: Potential equity interest. Boni:ADC Therapeutics: Employment, Other: Potential equity interest. O'Connor:ADC Therapeutics: Research Funding.

In vivo studies on the ameliorative effect of coconut water against carbon tetrachloride induced toxicity in rats

Purpose Coconut water is used in folklore medicine for oral rehydration, treatment of childhood diarrhoea, gastroenteritis and cholera, and is also known to possess antioxidant properties. Objective In this study, we examined the ameliorative potentials of coconut water on carbon tetrachloride (CCl4) induced toxicity in rats. Materials and methods Rats were randomly assigned into separate cages according to the sex of 5 groups. Groups 2–5 were intraperitoneally injected a single dose of 1 mL/kg CCl4 diluted in olive oil. Only 3, 4 and 5 were orally given 2, 4, 6 mL/kg coconut water respectively, whereas groups 1 and 2 received distilled water. Results Treatment with coconut water significantly (p < 0.05) increased red blood cell, packed cell volume, haemoglobin, high-density lipoprotein, glutathione, superoxide dismutase, catalase, total protein, and albumin compared to the negative control in both sexes of the rats. Furthermore, platelets, white blood cells, urea, low-density lipoprotein, triglyceride, total cholesterol, malondialdehyde, bilirubin, alkaline phosphatase, alanine and aspartate transaminases decreased significantly (p < 0.05) compared to the negative control in both male and female rats. Conclusion Thus, coconut water supplementation may reverse CCl4 induced toxicity and distortions on haematological parameters, lipid profile and antioxidant enzymes, liver and kidney biomarkers in rats.

The Effect of Pluchea indica (L.) Less. Tea on Blood Glucose and Lipid Profile in People with Prediabetes: A Randomized Clinical Trial.

Objective: Diabetes mellitus and dyslipidemia are currently increasing dramatically, and conventional medicine in the treatment of them has limited efficacies and serious adverse effects. Pluchea indica (L.) Less. tea (PIT) is widely consumed as a health-promoting drink in Southeast Asia. This study aimed to investigate whether P. indica tea has antidyslipidemic and antihyperglycemic effects and toxicity in humans. Design: A randomized clinical trial. Setting/Location: Nakhonratchasima, Thailand. Participants: Forty-five participants with prediabetes. Interventions: Participants were randomized to receive placebo tea, 1.5 g of PIT, and 1.5 g Camellia sinensis tea (green tea, CST) once daily for 12 weeks. Outcome Measurements: The oral glucose tolerance test (OGTT), total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT), alkaline phosphatase (ALP), and complete blood count (CBC) before and after treatment were investigated. Results: The results showed that PIT significantly ameliorated hyperglycemia and significantly lower serum TG (109.22 ± 5.21 mg/dL) and LDL-C (122.20 ± 3.67 mg/dL) than placebo (145.56 ± 8.18 and 142.07 ± 8.58 mg/dL, respectively) (p < 0.05). Moreover, PIT exhibited serum TG (109.22 ± 5.21 mg/dL) significantly lower than CST (124.38 ± 4.70 mg/dL) (p < 0.05). In addition, the serum HDL-C of PIT (57.56 ± 3.05 mg/dL) was significantly higher than the placebo (46.44 ± 2.47 mg/dL) (p < 0.05). Furthermore, the toxicity testing showed that no significant difference in BUN, creatinine, ALT, ALP, and CBC of PIT-treated group compared with the placebo (p > 0.05). Conclusions: These results suggest that PIT may ameliorate hyperglycemia and dyslipidemia in prediabetes people. It may not be toxic to the kidney, liver, and blood. So, PIT has the potential to develop to be a health-promoting tea or herbal medicine for hyperglycemia and dyslipidemia prevention.

Cardiorespiratory and haematologicalparameters of healthy french bulldogs

Brachycephalic dogs have a normal lower jaw and a receded upper jaw, and these dogs are predisposed to nostril stenosis, elongated palate, tracheal hypoplasia and hyperthermia due to heat stress. Giventhese characteristics, these dogs are more predisposed to respiratory and cardiovascular disorders. The popularity of brachycephalic dogsthathave a greatertendency for cardiorespiratory disorders, such as French bulldogs,has increased recently; however, studies on the cardiorespiratoryand haematological parameters in this breedare lacking. Thus, the present study sought to evaluatethe cardiorespiratory and haematological parameters of healthy French bulldogs to standardize normal values forthisbreed. Thirty-six French bulldogs wereused without predilection for age or sex, and the following parameters were evaluated: temperature (T), heart rate (HR), respiratory rate (RR), erythrogram, leukogram, total plasma protein, plasmatic fibrinogen, blood platelet count, urea, creatinine, alkaline phosphatase (AP) and alanine aminotransferase (ALT). The mean and standard deviation wereas follows: T°C (38.3±0.4), HR (111.1±27.0) beats per minute, RR (54.8±32.5) breaths per minute, erythrocyte count (7.3±1.2x106), haemoglobin (16.9±2.8 g/dL), haematocrit (48.9±7.7%), MCV (67.6±2.4fL), MCH (23.3±0.7 pg), MCHC (34.6±0.8%), RDW-CV (9.3±0.9; 9.2-12.0%), total leukocytes (11009.7±2907.3/mm3), band neutrophils (250.0±260.4/mm3), segmented neutrophils (7094.4±2307.3/mm3), eosinophils (589.7±561.3/mm3), lymphocytes (2020.8±1457.5/mm3), monocytes (987.6±528.4/mm3), total plasma protein (6.9±0.5 g/dL), plasmatic fibrinogen (274.1±96.5 mg/dL), blood platelet count (366.4±88.5/mm3), urea (35.2±12.6 mg/dL), creatinine (0.8±0.2/mg/dL), AP (49.1±25.8U/L),ALT (36.2±12.3U/L). The haematological parameters and heart rate were within the normal values for the species, but the respiratory rate values (54.8±32.5 breaths per minute)were greater than the normal averageof10 to 30 breaths per minute. We conclude thatthehaematological parameters and heart rateof healthy French bulldogs arewithin the normal limit for dogs; however, the respiratory rate is above referencevalues, reinforcing the notion that dogs of this breed, although healthy,exhibitan increasedrisk of respiratory disorders

A phase I study of a TGF-β receptor I kinase inhibitor YL-13027 in patients with advanced solid tumors.

3098 Background: Transforming growth factor beta (TGF-β) is upregulated in the majority of tumors, promoting tumor cell proliferation, differentiation, and, modulation of the tumor microenvironment. YL-13027, a small molecule inhibitor of type 1 receptor of TGF-β, is a potent highly selective oral agent that downregulates TGFbR1-dependent pathways in tumor cells. YL-13027 dosed into tumor bearing animals drives tumor growth inhibition and interruption of metastasis. In this first-in-human phase1 study, we characterized the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK) and preliminary efficacy of YL-13027 in patients with advanced solid tumors. Methods: YL-13027 tablets were administered orally, twice daily under fasted conditions for 28 days, for at least two 28 day cycles until disease progression, unacceptable toxicity or withdrawal from the study. Starting with an initial dose of 60 mg, dose escalation in a 3+3 design, and pre-determined PK assessments were applied. Adverse events (AEs) were graded by NCI-CTCAE v5.0. PK analysis was performed using a non-compartmental method. Efficacy was evaluated according to RECIST1.1. Results: As of January 18th 2021, thirteen patients were enrolled sequentially to Cohort-1 (60 mg, n = 2), Cohort-2 (120 mg, n = 1), Cohort-3 (180 mg, n = 3), Cohort-4 (240 mg, n = 4) and Cohort-5 (300 mg, n = 3), having gastrointestinal (n = 9), esophageal (n = 1), gallbladder (n = 1), lung (n = 1) and breast (n = 1) carcinomas. These patients had prior systemic antitumor standard therapies, including multi-line chemotherapy, radiation therapy, molecular targeted therapy, immunotherapy, or surgery. Twelve patients completed the cycle 1 safety observation period, with no cardiovascular toxicities or other DLTs observed. The MTD was not reached. Twelve patients experienced AEs possibly related to YL-13027. The most frequent related TEAEs (all grades/grade ≥3) were gamma-glutamyltransferase increased (38.5%/7.7%), haemoglobin decreased (38.5%/0%), blood alkaline phosphatase increased (23.1%/7.7%), aspartate aminotransferase increased (23.1%/0%) and blood phosphorus decreased (23.1%/0%). A maximum YL-13027 plasma concentration was reached within 2h post dose, and the mean elimination half-life was 4.2h in the steady state. Six subjects were evaluable for efficacy. One triple-negative breast cancer (TNBC) subject (Cohort-4) acquired a Partial Response (38.8% reduction of the target lesion), with the response exceeding 4 cycles, and YL-13027 treatment is continuing. The TNBC patient’s tumor profile indicated genomic mutations of EGFL7p.Q256H(13.50%), TP53p.E51*(10.90%) and NF1p.L21V(8.70%) from the initial tumor specimen at diagnosis. Conclusions: YL-13027 is well tolerated and further clinical investigation is warranted. Clinical trial information: NCT03869632.

A phase Ib study of proxalutamide (GT0918) in women with androgen receptor-positive metastatic breast cancer.

1019 Background: Androgen receptor (AR) is an emerging prognostic marker and therapeutic target in breast cancer. AR is expressed in 60% to 80% of breast cancers. Recent studies have shown the association between AR signaling and tumor carcinogenesis in breast cancer, suggesting AR pathway as a potential target for breast cancer treatment. However, no AR targeting therapies have been approved for treating breast cancer. GT0918 is a new chemical entity of AR antagonist with possible AR down-regulation. We had finished the phase I study and submitted the paper. Here we present a multicenter, open-label phase Ib trial assessing the safety and efficacy of GT0918 in women with AR positive metastatic breast cancer. The primary objective is to evaluate the efficacy of GT0918. The secondary objectives are to assess its safety and to explore the relevant biomarkers. Methods: This is an expansion study of a phase I dose-escalation trial. In this phase Ib study, only patients with AR positive metastatic breast cancer were enrolled. All eligibled patients would take GT0918 orally once a day, of a 28 -day cycle. After 2 cycles’ safety and tolerability assessment, patients could choose to continue their treatment until they experience disease progression, intolerable toxicities, death, or withdrew consent. The primary efficacy endpoints were 8-week disease control rate (DCR) and 16-week DCR. The secondary efficacy endpoint was progression free survival (PFS). Results: In total, 45 patients were enrolled in the study at 200mg (n = 30) and 300mg (n = 15) doses. The most common (≥10%) treatment-related adverse events (AEs) were asthenia (42.2%), aspartate aminotransferase increased (26.7%), blood cholesterol increased(17.8%), alanine aminotransferase increased (17.8%), decreased appetite (17.8%), blood triglycerides increased (13.3%), blood lactate dehydrogenase increased (13.3%), anaemia (13.3%), blood alkaline phosphatase increased (11.1%), gamma-glutamyltransferase increased (11.1%), urinary tract infection (11.1%). Grade 3/4 AEs were reported in 9 patients (20%). No treatment-related deaths occurred. The 8-week and 16-week DCR were both 22.2% (n = 10) (95% CI 10.08%, 34.37%). The median PFS was 1.8 months (95% CI 1.8, 1.9) in all patients. 12 out of 45 (26.7%) were triple negative breast cancer cases. The median PFS was 1.9 months (95% CI 1.7, 9.1), 4 out of 12 patients (33.3%) &gt; 6 months, 2 out of 12 patients (16.7%) &gt; 9 months. Conclusions: GT0918 has been shown to be well tolerated and may provide potential clinical benefits to AR positive metastatic breast cancer patients. This study demonstrated triple negative in AR positive patients had more benefit. Clinical trial information: NCT04103853 .

Results from the phase Ib of the SENSITIZE trial combining domatinostat with pembrolizumab in advanced melanoma patients refractory to prior checkpoint inhibitor therapy.

9545 Background: Anti-PD-1 +/- anti-CTLA4 antibodies are the current standard of care immunotherapy for advanced melanoma. However, a significant proportion of patients do not achieve disease control. Epigenetic modulation, particularly histone deacetylase (HDAC) inhibition, can overcome tumor escape mechanisms and thus might increase the susceptibility to immunotherapy. Methods: Advanced unresectable/metastatic cutaneous melanoma patients primary refractory or non-responding to prior checkpoint inhibitor (CI) therapy were treated with domatinostat at 5 different dose levels (DL) (100 mg (QD), 200 (QD), and 200 mg (BID) using two different schedules (D1-14 and D1-21 q3w) in combination with pembrolizumab (2 mg/kg) q3w to evaluate safety and tolerability. Tumor assessments were performed every 12 weeks and assessed using irRECIST. Sequential tumor biopsies were taken for gene expression analysis and peripheral blood for pharmacokinetic (PK) analysis. Results: We report on preliminary results from the phase Ib part of the ongoing study, data cut-off Feb 1st, 2021 a total of 40 patients have been enrolled. Patient characteristics show that the median number of pretreatments at stage IV was 3, 65 % of patients stage M1c (AJCC 7 or 8) and 35 % with elevated LDH at trial inclusion. Treatment emergent adverse events (AEs) related to domatinostat reported in ≥ 10% of patients were: diarrhea (23%), nausea (20%), fatigue (20%), rash (15%), pyrexia (13%), blood alkaline phosphatase increased (13%), vomiting (10%), dyspnea (10%), all grade 1 and 2 - except one maculo-papular rash grade 3. In total, 8 patients (20 %) developed ≥ grade 3 AEs, with no treatment-related deaths. Patterns of AEs resembled the known safety profiles of domatinostat and pembrolizumab with no increase of immune related AEs for the combination. Maximum tolerated dose was not reached. Four patients discontinued treatment per protocol due to AEs grade 3. We observed clinical activity with 1 complete response, 2 confirmed partial responses and 9 stable diseases (6 confirmed), resulting in a disease control rate of 30% in highly pretreated patients throughout all DLs. Notably, 3 out of 7 patients achieved disease control in DL 3 (domatinostat 200 mg BID D1-14, q3w) and were on treatment ≥ 1.5 years, indicating a trend of dose-dependent clinical activity. Domatinostat treatment resulted in a trend to higher intra-tumoral expression of MHC/APM genes and a more inflamed tumor microenvironment reflecting enhanced T cell infiltration. Conclusions: The combination of domatinostat and pembrolizumab was safe and well tolerated. The observed clinical activity in advanced melanoma patients refractory to previous checkpoint inhibition and the favorable translational findings warrant further development of domatinostat in combination with CI in melanoma and beyond. Clinical trial information: NCT03278665.

Oregano essential oil enhanced the growth performance, immunity, and antioxidative status of Nile tilapia (Oreochromis niloticus) reared under intensive systems

The current goal of aquaculture sector is to increase stocking densities while sustaining the aquatic animal's health. Here Nile tilapia were allocated in 27 aquaria (100L) at 3 different stocking densities: low rearing density (LRD) at ~1.15 kg/m3; medium rearing density (MRD) at ~2.3 kg/m3; and high rearing density (HRD) at ~4.6 kg/m3. Each stocking density was fed one of 3 oregano essential oil (OEO) levels (0, 1, or 2 mL/kg) in their diets for 12 weeks. Dissolved oxygen was stable in all treatments until the 4th week, then declined from the 6th week until the end of the trial, with severe reduction in the HRD. Total ammonia, nitrite, and nitrate were markedly increased in the HRD groups, regardless dietary OEO. Stocking density was a significant factor in the final body weight (FBW), weight gain (WG), specific growth rate (SGR), and feed conversion ratio (FCR) indices of the fish, and dietary OEO was a significant factor in the FBW and WG (P < 0.05). Stocking density and dietary OEO were significant factors in hemoglobin, red blood cells, and white blood cells (WBCs) levels, and the interaction between the two factors significantly influenced the WBCs (P < 0.05). Blood cortisol, glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, and creatinine increased with increasing stocking densities, with lower levels in the fish fed OEO than the fish fed the basal diet (P < 0.05). The superoxide dismutase (SOD), lysozyme, and phagocytic activities were significantly decreased with increased stocking density, but dietary OEO had no influence on SOD (P < 0.05). The nitic oxide (NO), glutathione reductase (GR), and myeloperoxidase (MPO) were significantly impacted by both the stocking density and dietary OEO (P < 0.05). Fish reared under high stocking densities and fed OEO-free diets had lower NO, GR, and MPO than fish fed dietary OEO (P < 0.05). In conclusion, the incorporation of dietary OEO is recommended to relieve the impacts of high stocking densities on Nile tilapia aquaculture.