Changes In Hematological Parameters Research Articles

Dinâmica hematológica de cavalos produtores de soro antibotrópico, durante o processo de imunização

ABSTRACT Ophidic accidents caused by snakes of the genus Bothrops are responsible for 70% of notifications in the country. The antiophidic serum is the specific antidote against envenomation caused by these snakes. Aiming to evaluate the health status of horses producing antibotropic serum, the hematological variables and serum iron were delineated along the protocol of three immunizations. The animals were evaluated at 17 experimental moments, being: control (before the immunogen application), four hours, 24h, 48h, 72h and seven days after inoculations, for each immunization. There was a significant decrease in erythrocyte, hemoglobin, and hematocrit values after the second immunization. Serum iron values showed significant decreases during the three immunizations. Significant decreases in lymphocyte values were noted in the first two immunizations, while there was a significant increase in neutrophil values during all three immunizations. Eosinophils, monocytes, and basophils did not show significant difference throughout the three immunizations. The immunization protocol described in this study caused an inflammatory reaction at the site of immunogen application and transient changes in hematological parameters and iron levels, as by the end of the immunization protocol, the variable values returned the reference levels.

Biochemical Indicators of Blood and Milk in the Cows Affected by Latent Mastitis

Latent mastitis harms the health of animals, their milk production, and the quality of milk. In cows affected by this disease sharp changes in hematological parameters, and biochemical parameters of blood and milk, which is the focus of our research. This work studies the morphological and biochemical parameters of blood and the biochemical parameters of milk in dairy cows affected by latent mastitis. The research was performed in several farms and farm households of Kotayk and Ararat regions, as well as in the ANAU Research Center of Veterinary Medicine and Veterinary Sanitary laboratories. The research outcomes prove that latent mastitis significantly impacts the composition of blood and milk components. Data obtained during the research enables a better understanding of the causes of mastitis as well as the necessity of using informative diagnostic methods in farm veterinarians’ practices.

Lactation related changes of haematological parameters of female dromedary camels reared under semiintensive farming system in Algerian extreme arid region

Lactation related changes of haematological parameters of female dromedary camels reared under semiintensive farming system in Algerian extreme arid region

Changes in hematological parameters during different stages of lactation in Surti buffaloes

Changes in hematological parameters during different stages of lactation in Surti buffaloes

Investigating the Impact of Indoor Air Pollutants on Allergies and Eczema in Craftspeople

The aim of this study was to investigate the possible association between exposure to air pollutants in various industries and the occurrence of blood abnormalities and allergic conditions to achieve this we performed comprehensive blood counts and occupational air quality tests. Blood samples were collected from participants in five occupations: bakers, carpenters, blacksmiths, painters, dyers, and construction workers. These projects were selected because of their potential to handle various air pollutants. Blood tests were then performed for five major parameters including immunoglobulin E (IgE), white cell count (WBC), hemoglobin (Hb), and neutrophils (Neu), lymphocytes (Lym), in addition to blood tests we also measured air quality in it stakeholders workplaces. This will likely require monitoring specific pollutants known to be relevant to each project, including: PM10 and PM2.5, formaldehyde, VOC, carbon dioxide (CO2), and carbon monoxide (CO), formaldehyde was the highest, and VOC, bakers and artisans had CO2 and CO levels above permissible limits, construction workers had the highest levels of PM2.5. Blood tests showed abnormalities in several areas, the baker showed elevated immunoglobulin-E (IgE) levels, indicative of possible allergic reactions, and white blood cell counts (WBC), hemoglobin (Hb), neutrophils and lymphocytes are highest in the medical profession. These findings suggest an association between occupational exposure to air pollutants and changes in hematological parameters, although asthma symptoms have also been reported in other studies.

Effect of 90 Days Sub-chronic Administration of Omeprazole (A Proton Pump Inhibitor) on Haematological, Biochemical, Antioxidant, Reproductive and Histopathological Parameters in Male and Female Rats

Abstract Despite the widespread use of omeprazole (OME), there are still concerns about its long-term safety and tolerability, especially with long-term or indiscriminate use. This study was designed to evaluate the effect of 90 days sub-chronic administration of OME on haematological, biochemical, antioxidant, reproductive and histopathological parameters in male and female rats. Forty-eight (48) Wistar rats of both sexes were divided into 4 groups of 6 male and 6 female animals each. Group I received 10 mL/kg normal saline, while Groups II – IV received 0.12 mg/kg, 0.57 mg/kg, 2.85 mg/kg of OME respectively for 90 days. At the end of 90 days, 5 mL blood sample was collected, and vital organs were harvested for relevant analyses. In this study, OME did not elicit any significant (P>0.05) change in the body weight or weight of vital organs, but elicited a significant (P<0.05) reduction in sperm count at the supratherapeutic dose (2.85 mg/kg). The supratherapeutic dose of OME produced significant increase in cholesterol (P<0.0001) and LDL (P<0.0001) in female rats. OME did not generally produce a significant change in haematological parameters. OME elicited a significant decrease in CAT (P<0.05) in female and combined animals. Additionally, histopathological presentations of vital organs were generally non-abnormal. From this study, it can be concluded that long term administration of OME is generally safe and tolerable, especially at lower doses. Findings from this study suggest that OME may potentially induce changes in sperm characteristics (in relation to male rats), hepatoxicity, hypercholesteremia, hyperlipidemia and thrombocytosis over a long duration, at higher doses and especially in female animals.

Clinical Outcomes of Patients with Hematologic Malignancies Receiving Bendamustine Lymphodepletion Prior to CAR-T Cell Infusion

CAR-T cell therapy has revolutionized the treatment of adult patients with relapsed/refractory (r/r) non-Hodgkin lymphomas (NHL) and multiple myeloma (MM). While lymphodepletion (LD) with fludarabine/cyclophosphamide (flu/cy) has been the standard, the fludarabine drug shortage has caused a shift toward the use of bendamustine as an alternative. This study expands upon previous investigations evaluating bendamustine as a LD agent prior to CART therapy. We conducted a retrospective study of 48 patients with r/r NHL (marginal zone lymphoma (MZL), diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL)) and MM who received bendamustine LD prior to treatment with commercial CART products at the UPMC Shadyside Hospital between 07/2022-04/2023. Data were collected using chart review and analyzed by descriptive statistics. Responses for NHL and MM were assessed based on the Lugano 2014 criteria and the International Myeloma Working Group consensus criteria, respectively. Toxicities were evaluated based on the American Society for Transplantation and Cellular Therapy consensus grading and the Common Terminology Criteria for Adverse Events. 33 patients with NHL (24 with DLBCL, 2 with MZL, 2 with FL and 5 with MCL) and 15 with MM, were included with a mean age of 65.8 years. The median number of prior therapies was 2 [1 - 5] for NHL, and 5 [4 - 10] for MM. In the NHL cohort, 14/33 patients were treated in the second line. Among NHL patients, 5/33 patients received brexucabtagene autoleucel, 24/33 axicabtagene ciloleucel (axi-cel), and 4/33 lisocabtagene maraleucel (liso-cel). Among MM patients, 2/15 patients received idecabtagene vicleucel, and 13/15 ciltacabtagene autoleucel (cilta-cel). Grade (G) 1-2 CRS occurred in 23/33 of NHL and 14/15 of MM patients, without any reported G3 CRS. ICANS was reported in 9/33 (3 G3) of NHL and 7/15 (1 G3) of MM patients. The overall response rate (ORR) in MM patients was 12/15, with 6/12 achieving complete response (CR) or stringent CR (sCR) and 6/12 a very good partial response (VGPR), and only 1/12 progressing after a response. In the NHL cohort, we evaluated the ORR for every subtype. The ORR was 16/24 (11/16 CR and 5/16 PR) in DLBCL, 1/2 (CR) in MZL, 3/5 (all CR) in MCL, and 2/2 (all CR) in FL. Only 3 patients with DLBCL, 1 with MZL and 1 with MCL eventually progressed after a response. These response results are comparable with prior CART studies of flu/cy LD that have shown ORR range of 72-73% (CR 51-54%) for DLBCL ( Locke F, Lancet Oncol., 2019; Abramson JS, Lancet 2020), 91% (CR 60%) for FL ( Jacobsen CA, Lancel Oncol. 2022), and 98% (sCR 78%) for MM ( Berdeja JG, Lancet 2021). Next, we evaluated the change in hematologic parameters after LD. Absolute lymphocyte counts (ALC) showed mean decreases of 66.8% (± 28.4%) in NHL and 69.3% (± 16.4%) in MM from pre-LD to the day of CAR-T infusion (D CART), with median time-to-nadir (TTN) post-D CART of 1 [0-13] days in NHL and 1 [0-8] days in MM. We then compared the incidence of neutropenia in our cohort relative to historical controls treated with flu/cy LD. Neutropenia was seen in 80% of patients (G≥3, 68%) with axi-cel, 50% (G≥3, 50%) with liso-cel, and 100% (G≥3, 77%) with cilta-cel. This compares favorably to historical data with axi-cel, (86%; G≥3, 80%), liso-cel (63%; G≥3, 60%), and cilta-cel (96%; Gr≥3, 95%). Table 1 illustrates the grades of cytopenias and ANC nadir and TTN post-D CART in our study. Finally, we investigated the mean change in inflammatory markers as a surrogate of CAR-T activation and expansion. CRP showed a median increase of 2.8-fold [0 - 66.5] in a median of 5 [0-55] days in NHL, and a median increase of 4.6-fold [0.22 - 74.9] in a median of 8 [2-15] days in MM. Ferritin had a median increase of 1.2-fold [0- 50] in median of 9 [0-171] days in NHL, and median increase of 3.8-fold [0.63 - 59.4] in median 10 [0-148] days in MM. In conclusion, bendamustine is a successful LD agent prior to CAR-T infusion, yielding response rates comparable to historical controls in NHL and MM. Notably, our study reveals a favorable safety profile with a lower rate of high grade cytopenias than was seen in the pivotal trials using flu/cy LD. These findings are reassuring regarding the use of bendamustine as an alternative LD agent in the face of the ongoing fludarabine drug shortage. Further studies assessing CART copy numbers and persistence of CART are needed.

One-Year Safety and Efficacy of Mitapivat in Sickle Cell Disease: Follow-up Results of a Phase 2, Open-Label Study

Background Targeting the primary pathogenic event of sickle cell disease (SCD), polymerization of deoxygenated sickle hemoglobin (HbS), may prevent downstream clinical events. Mitapivat, an oral allosteric activator of pyruvate kinase (PK), has shown therapeutic potential by increasing adenosine triphosphate (ATP) and decreasing 2,3-diphosphoglycerate (2,3-DPG), a glycolytic red blood cell (RBC) intermediate. In addition to improving anemia and hemolysis, mitapivat may reduce HbS polymerization and inhibit sickling by decreasing 2,3-DPG levels in patients with SCD. In the previously reported 8-week dose-finding period (DFP) of this phase 2 study, mitapivat was well tolerated and showed efficacy in SCD ( Van Dijk et al. Am J Hematol. 2022). Here, the safety and efficacy of treatment with mitapivat in patients with SCD from the 1-year fixed-dose extension period (FDEP) are reported (EudraCT 2019-003438-18, ESTIMATE study). Methods The ESTIMATE study is a phase 2, investigator initiated, open-label study in which subjects ≥16 years with SCD (HbSS, HbS/β 0, HbS/β +) with a baseline hemoglobin (Hb) >4.0 g/dL and ≤11.1 g/dL, no chronic transfusion and adequate organ function were eligible. After the 8-week DFP in which patients were dosed mitapivat 20 mg, 50 mg or 100 mg twice daily depending on safety, patients could continue in the 1-year FDEP. The primary endpoints were safety, evaluated by frequency and severity of adverse events (AEs), and efficacy of mitapivat including the evaluation of a hematological response (improvement in mean Hb level of ≥1 g/dL compared to baseline during the FDEP). RBC sickling was evaluated by oxygen gradient ektacytometry (point of sickling, Lorrca). Secondary endpoints included changes in hematological parameters including Hb, absolute reticulocyte count (ARC), total bilirubin, lactate dehydrogenase (LDH), levels of ATP and 2,3-DPG and Hb-oxygen affinity, as reflected by the oxygen tension at which Hb is 50% saturated (p50, Hemox Analyzer). Exploratory endpoints included changes in annualized rates of vaso-occlusive events (VOEs) and annualized SCD-related hospital admission days. Intention-to-treat analysis was performed using IBM SPSS Statistics (version 27.0.0.0) and Graphpad Prism (version 9.3.0) with the paired sample t-test or Wilcoxon signed-rank test used when appropriate. Results In total, ten patients were included in this study. Safety analysis showed mostly mild treatment-emergent adverse events (most commonly [n>2 patients]: transaminase increase [all grade 1] and headache [grade 1-2]). Apart from the non-treatment-related serious adverse event (SAE) of a urinary tract infection in the DFP in a patient who was lost to follow-up afterwards, one non-treatment-related SAE occurred in the FDEP in a patient who died of massive pulmonary embolism due to COVID-19. Importantly, sustained improvements in Hb level (mean increase: 1.1 ± 0.7 g/dL; p=0.0014) were seen in the nine patients who continued treatment with mitapivat 50 mg twice daily (n=2) or 100 mg twice daily (n=7) in the FDEP (Table 1). These improvements were accompanied by decreases in markers of hemolysis (ARC, total bilirubin and LDH) (Table 1). On a cellular level, the ATP/2,3-DPG ratio and Hb-oxygen affinity increased significantly, and RBC sickling was reduced, though non-significantly (Table 1). In addition, the annualized rate of vaso-occlusive events reduced significantly from 1.33 ± 1.32 to 0.64 ± 0.87 (p=0.0489) when combining the DFP and FDEP (Table 1 and Figure 1). Conclusion Overall, this study demonstrated long-term safety and efficacy of treatment with mitapivat in SCD, warranting further evaluation in the ongoing phase 2/3 RISE UP study (ClinicalTrials.gov NCT05031780).

Erythrocyte Indices Variations In Under Five Children As A Result Of High Plasmodium Falciparum Parasitaemia

Nigeria accounts for 31% of the 619,000 malaria-related deaths recorded worldwide, according to the World Malaria Report 2022. Malaria caused by Plasmodium falciparum causes significant changes in haematological parameters and indices. The study aimed to observe erythrocyte indices and haemoglobin concentration variations in children with Plasmodium falciparum parasitaemia, evaluate the correlation between parasite count and indices, and assess their predictive roles. We analysed 194 children (≤ 5 years old) suspected of malaria and collected 5 ml of whole blood samples for analysis. The samples were used to prepare thin and thick blood films for qualitative and quantitative assays. A CBC was carried out to estimate HGB concentration and erythrocyte indices. The case and control group had a mean difference statistically significant at (P<0.001). MCV [case group (72.26±4.83), control group (85.00±4.48)]; MCH [case group (23.82±2.51), control group (28.85±2.02)] and HGB [case group (100.78±14.84), control group (135.65±9.95). Pearson correlation showed weak negative statistical significance at (P<0.05) for MCV, MCH, MCHC and HGB in the range of (-0.38) – (-0.218). Regression analysis indicated that parasite count predicted MCV, MCH, MCHC and HGB at (P<0.05); R values at (0.283, 0.272, 0.326 and 0.308, respectively). When considering age and parasite count as predictive variables, we obtained R values of 0.285, 0.282, 0.326, and 0.328 for MCV, MCH, MCHC, and HGB, respectively. Research results show a significant relationship between Plasmodium falciparum parasitaemia and variations in erythrocyte indices with haemoglobin concentration in children at significant levels.

Durable Clinical Benefit with Ker-050 Treatment: Findings from an Ongoing Phase 2 Study in Participants with Lower-Risk MDS

Background: In myelodysplastic syndromes (MDS), defects occur at multiple stages of hematopoiesis. Available Erythropoiesis Stimulating or Erythroid Maturation Agents (ES/EMAs) target early or late stages of erythropoiesis, respectively, and are only effective in subsets of patients. For patients with high transfusion burden (HTB) who have diminished erythropoietic capacity and a worse prognosis, ES/EMAs show limited efficacy and durability of response (DOR). KER-050 is an investigational, modified activin receptor type IIA ligand trap designed to inhibit select TGF-β superfamily ligands (activins A, B, GDFs 8, 11) that is being evaluated in diseases with ineffective hematopoiesis (IH), including MDS and myelofibrosis. Preclinical studies demonstrated that KER-050 increased erythropoiesis and thrombopoiesis and acted on early- and late-stage erythropoietic and megakaryocyte progenitors. By eliciting effects on hematopoiesis across multiple differentiation stages and cell lineages, KER-050 has the potential to address the complex nature of IH and to provide robust and sustained hematological improvement in patients with MDS who have limited treatment options, including those with HTB or non-ring sideroblast (RS) MDS. Methods: Analyses evaluating KER-050 at the recommended Part 2 dose (RP2D; 3.75 - 5 mg/kg q4wk) in participants with lower-risk (LR), RS+ or non-RS MDS from an ongoing Phase 2 study (NCT04419649) are presented as of a data cutoff date of April 3, 2023. The primary endpoint evaluates the safety and tolerability of KER-050. Secondary endpoints of modified IWG 2006 Hematological Improvement-Erythroid (HI-E) and transfusion independence (TI) ≥8 weeks are presented for participants who received ≥24 weeks of treatment or discontinued. DOR and changes in hematological parameters for participants with ongoing TI are presented for the first time. Results: At baseline, most participants receiving KER-050 at the RP2D (74.6%) required regular transfusions (≥2 RBC units/8 weeks); 52.5% of RP2D participants had HTB (≥4 RBC units/8 weeks) and 20.3% had ≥8 RBC units/8 weeks (Table 1). The median treatment duration was 166 days (range 6 to 649). Most participants (89.8%) had at least 1 treatment-emergent adverse event (TEAE), and 32.2% had TEAEs considered treatment-related (Table 1). The most frequently observed TEAEs in ≥15% of participants were fatigue (22.0%), nausea and diarrhea (18.6% each), epistaxis (16.9%), and COVID-19 and dyspnea (15.3% each). A minority of participants (10.2%) had TEAEs that led to treatment discontinuation. Consistent with prior data, rates of TI for ≥8 weeks were similar regardless of baseline transfusion burden or RS status (Table 1). Among TI responders, 72.7% maintained TI for ≥24 weeks (data not shown), and the median DOR was not yet evaluable as more than half (6/11) had ongoing TI as of the cutoff date (Figure 1). Five of the 6 (83.3%) participants with ongoing TI had HTB at baseline, including one participant with a baseline transfusion burden of 11 RBC units/8 weeks, and all 3 responders with ongoing TI for >60 weeks. One participant with HTB and non-RS MDS had ongoing TI for >72 weeks with a steady increase in hemoglobin from 8.4 to 11.8 g/dL. Erythroid responses were not at the expense of other cell lineages, as levels of platelets and neutrophils generally did not decrease (Figure 1). In fact, 44.1% of participants overall experienced a sustained (≥8 weeks) mean increase in platelet count of ≥30 x 10 9 within the first 24 weeks. Sustained decreases in ferritin were observed in parallel with increases in soluble transferrin receptor (Table 1), and for 3 participants, iron chelator therapy (ICT) was able to be discontinued. Investigation into changes in serum ferritin and ICT with KER-050 treatment will continue as cohorts of participants with MDS and iron overload are enrolled. Summary: Updated findings from this ongoing Phase 2 study in LR MDS continue to show that KER-050 is generally well-tolerated and has potential to elicit sustained hematological improvements in a broad population of participants with LR MDS, including those with HTB. New data reveal an encouraging DOR, with observed preservation or improvement of multilineage hematopoiesis and sustained decreases in ferritin manifesting clinically with discontinuation of ICT. The study is ongoing and an update with the latest data will be provided at the time of presentation.

Mildronate Ameliorates Kidney Function and Reduces Inflammation in SCD Mice

INTRODUCTION:Sickle cell disease (SCD) is a genetic hemoglobin disorder characterized by hemolytic anemia, vaso-occlusive crisis and inflammation that affects organs such as the kidney, liver, brain, spleen, and heart. SCD is driven by a mutation in the β-globin gene that causes sickling of red blood cells (RBCs). More than 50% of SCD patients are affected by chronic kidney diseases (CKD) and other comorbidities. Vasculopathy is caused by hemolysis-related endothelial dysfunction and inflammation, which collectively contribute to the development of renal disease. Mildronate (also known as Meldonium) is an anti-ischemic and cardio protecting medication approved in Eastern Europe. Mildronate facilitates a switch from fatty acid oxidation to less oxygen-intensive glycolysis that allows less oxygen consumption by peripheral tissues and higher oxygenation of heart. We hypothesized that mildronate administration would reduce tissue hypoxia and decrease inflammation in SCD mice. METHODS: The study was approved by the Institutional Animal Care and Use Committee at Howard University (IACUC). We employed the Townes SCD mouse model, which mimics SCD complications. SCD and control mice were injected with mildronate (400 mg/kg in saline) intraperitoneally or saline as vehicle control over the course of ten days. Blood and plasma were collected and used for hematological parameters analysis. Cytokines were measured by Bio-plex suspension array in plasma and real-time RT-PCR or ELISA in organs. Protein expression of HO-1, HIF-1α, NFκB and NRF2 was measured by Western blot. The effect of Mildronateon systemic and renal oxidative stress was measured by malondialdehyde (MDA) using ELISA (Abcam). RESULTS: We observed significant reduction in the cytokine's levels of IFN-γ, IL-1, and TNF-α in plasma of SCD mice after mildronate injection. We also observed reduction in IL-6, IL-10 and IL-17 levels but differences were not statistically significant. There were no significant changes in hematological parameters (Hematocrit, MCV, MCH, CMCH, Erythrocytes, Hemoglobin) after mildronate injection. Also, we did not observe changes in MDA levels in plasma or kidney in SCD mice compared to control mice, both non-injected and mildronate injected. We further evaluated HO-1 and NRF2 protein expression by western blot and observed no significant differences between SCD mice with or without mildronate injection. In H&E staining, cortex glomerular area and medullar congestion area were significantly reduced after mildronate injection. We also observed reduction of proteinuria in SCD mice injected with mildronate. DISCUSSION: Our examination of the effect of mildronate showed decreases inflammation in the mildronate injected SCD mice evidenced by reduced levels of IFN-γ, IL-1, IL-17, IL-6, IL-10, and TNF-α in circulation. There was a slight decrease in the expression levels of Nrf2 and HO-1 after mildronate injection. HO-1 is crucial for the catabolism of hemoglobin and protects against tissue damage in hemolysis. The HO-1 promoter has binding sites for several transcription factors, including phosphorylated Nrf2. Previous studies from our lab showed increased HIF-1α expression in PBMCs obtained from SCD patients. Here we did not detect significant changes in NFκB-p65 or HIF-1α expression levels. While we expected mildronate to decrease the oxidative stress, we did not observe significant reduction in MDA levels in treated mice compared to control mice. CONCLUSION: Mildronate improved kidney function in SCD mice by reducing circulatory and renal inflammation. In future, we plan to assess in more details the mildronate's impact on kidney function and inflammation. ACKNOWLEDGMENTS: This work was supported by NIH grants 1R01HL125005, 5U54MD007597, and 1SC1HL150685.

Ameliorating effect of Calotropis procera methanol leaf extract against oxidative stress and lipid peroxidation induced by fipronil in Wister albino rats

The exposure of humans to oxidative stress inducing chemicals is on the increase due to global industrialization. It has become vital to source for solution by searching for medicinal plants with antioxidant potential. This study was carried out to evaluate the toxicological effect and the antioxidant potential of Calotropis procera in fipronil induced Wister Albino rats. Qualitative and quantitative phytochemical and antioxidant screenings of the leaf extract were conducted using standard laboratory protocols. Acute oral toxicity was conducted using Lorke's method to determine the LD50 of the plant extract. The sub-chronic toxicity was evaluated using the Organisation for Economic and Cultural Development method. The in vivo antioxidant potential of the plant extracts was determined using standard methods. Qualitative phytochemical analysis revealed the presence of saponins, flavonoids, phenols, cardiac glycosides, steroids, terpenoids and coumarines. Quantitative analysis revealed the amounts of saponins (32.67%), cardiac glycosides (7.6 mg/g), phenols (28 mg GAE/g), flavonoids (7.37 mg/g) and steroids (21.53 μg/mg) that were found. The LD50 was calculated to be 2154 mg/kg. Sub-chronic toxicity studies revealed insignificant (p>0.05) increases in body weight. Insignificant (p>0.05) changes in haematological parameters were also observed across treated groups compared to normal control. Liver and kidney function parameters were significantly (p<0.05) altered at higher (dose) of extract compared to normal control. In vivo antioxidant activity of the extract revealed strong antioxidant potentials due to significant (p<0.05) alteration of enzymatic (SOD, CAT, GSH and MDA) and non-enzymatic (vit C and E) antioxidants in the extract treated groups when compared to fipronil treated and normal control groups. Histological screening revealed that the liver and kidney tissues were significantly (p<0.05) altered at higher (dose) of extract administration. In conclusion, the present study validates the antioxidant potential and hence ameliorating effect of C. procera methanol leaf extract from toxic effects of phenyl pyrazole insecticides.

Anticancer Potential of the Leaf Extracts from the Selected Croton Species

The reported investigations were aimed at establishing anticancer potential of the leaf extracts from Croton dictyophlebodes (CDE), C. kilwae (CKE) and C. longipedicellatus ssp austrotanzanicus (CLE). In vitro cytotoxicity assays of the extracts were performed against human laryngeal cancer cell line (HEp-2) and human breast cancer cell line (MCF-7), while in vivo toxicological studies were done using Swiss albino mice (Mus musculus) following the Organization for Economic Cooperation and Development guideline number 423 of 2001. Results for in vitro assays revealed that CDE and CLE induced cytotoxicity to MCF-7 and HEp-2 cell lines at EC50 values of 86 and 63 µg/mL, respectively, while CKE was inactive to HEp-2 cells at 100 µg/mL. For in vivo studies, mice were given calculated doses based on globally harmonized standards and monitored for 14 days to observe signs of toxicity. Haematological analysis was also carried out to obtain information on changes in blood conditions. The findings showed that LD50 for CKE and CDE were > 2000 mg/kg, while for CLE was 175 mg/kg body weight (b.w.). The oral administration of CDE and CKE did not reveal significant changes in haematological parameters of treated mice, while CLE provoked some. Thus, the studied extracts may be considered potential cancer remedies with safety pre-cautions that warrant further investigations.

CLINICAL SAFETY OF IVERMECTIN TREATMENT IN NILE TILAPIA, Oreochromis niloticus

Ivermectin belongs to the group of avermectins, a group of macrocyclic lactones produced by Streptomyces avermitilis, this drug is widely used in the treatment of endoparasitoses and ectoparasitosis in different species of mammals around the world. Based on this need to develop an adequate sanitary management of fish farms and the therapeutic importance of macrocyclic lactones, this study aimed to evaluate the clinical safety of ivermectin administered orally as part of the feed for Nile tilapia (O. niloticus). For this, 56 tilapias (O. niloticus), ±100g, were placed in 7 aquariums (n=8) with a capacity of 100 L of water, supplied with running water devoid of chlorine, with the following treatments being preserved: T0 (Control, untreated), T1 and T2 (treated with 125 and 625µg/kg-1 of ivermectin, respectively). Blood samples were collected for hemogram, leukogram and evaluation of serum biochemical parameters, in addition to organs such as spleen, liver and kidneys (cranial and caudal) for somatic evaluation. The results admired an increase in serum levels of ALT, AST and glycemia, a reduction in cholesterol and triglyceride values ​​at the highest dose, in addition to a decrease in total protein levels and liver somatic analysis. There was no change in hematological parameters, while the leukocyte profile indicated a significant increase in total leukocytes in treated tilapia with lymphocytosis and neutrophilia.. Therefore, treatment with high doses of ivermectin can harm the health of Nile tilapia, requiring additional studies to establish safe therapeutic protocols for these animals.

First report of a patient with homozygous hemoglobin Ernz: Evidence to support a non-pathogenic variant

Hemoglobin Ernz (Hb Ernz) is a missense variant in β-globin caused by a Threonine to Asparagine substitution at the 123rd amino acid position and HBB c.371C > A in gene level. Hb Ernz has been classified as Uncertain Significance (VUS) by ACMG due to limited reports and the absence of any homozygote genotypes. In our study, we found eight cases of Hb Ernz by DNA sequencing of the β-globin gene during >20 years of Thalassemia Screening in individuals with borderline hematological parameters who were possible carriers of thalassemia or their spouses. We also report the first homozygote variant of Hb Ernz. Our findings suggest that the changes in hematological parameters observed in individuals with Hb Ernz are likely due to α-globin gene mutations rather than Hb Ernz itself. These findings support the reclassification of Hb Ernz as a benign variant in variant classification.

Hazardous Impact of Coal Dust on Hematological Parameters of Underground Coal Mine Workers

Due to the nature of their work, coal miners have historically faced significant exposure to large amounts of dust, placing them at a heightened risk. The present study was conducted to explore the hazardous effects of inhalation of coal dust on the haematological parameters of underground coal miners. 120 underground coal miners (60 workers having 5-10 years of experience and the other 60 having 10-20 years of experience) and 62 matched non-exposed to coal dust subjects as control from the locality were recruited for the study. After obtaining consent, different physiological parameters were measured, and blood was collected for assessment of haematological parameters. Observations revealed that there were lower mean values of total RBC count, haemoglobin level, MCV, PCV, MCHC and MCH in coal mine workers whereas mean values of Red Cell Distribution Width (RDW) and ESR were increased in the workers group. Further, coal dust exposure causes increased total leucocyte to count as well as a differential count of lymphocyte, neutrophil, monocyte, and eosinophil in the workers group but, a decreased differential count of basophils was detected among coal dust-exposed workers. All the changes in haematological parameters were found to occur experience-dependent and maximum changes were observed in workers having 10-20 years of working experience. There is a significant likelihood of coal mine workers experiencing changes in their blood composition, which suggests the harmful impact of coal dust on this group. Further, haematological parameters will help health professionals to screen any pathologic conditions and may help to prevent coal dust exposure-associated haematological disorders and complications thereof.

Efficacy of cell-free DNA as a diagnostic biomarker in breast cancer patients

Breast cancer is the most prevalent and leading cause of mortality worldwide among women. Cell-free DNA (cfDNA) analysis is an alternative quantitative approach to conventional methods for cancer diagnosis. The current research project aimed to determine the efficacy of cfDNA as a diagnostic biomarker in breast cancer patients in Pakistan. Eighty-four female breast cancer patients were selected as cases, and 152 healthy females as controls. Immunohistochemistry was performed to identify tumor biomarkers along with clinical profiling. cfDNA was extracted from serum using the phenol–chloroform method. The cfDNA level in the serum was estimated using Agarose Gel Electrophoresis and Nanodrop. SPPS version 25.0 was used to perform statistical analyses. The results showed that the cancer biomarkers were significantly associated with breast cancer. The changes in hematological parameters were insignificant, whereas the biochemical parameter variations between the cases and controls were statistically significant. A significant association of cfDNA level with breast cancer was observed. Further cfDNA levels and cancer biomarkers were not statistically significant. A significant correlation was observed between cfDNA and biochemical parameters, except for creatinine, whereas hematological parameters showed no significant correlation.ROC analysis declared cfDNA as an authentic diagnostic marker for breast cancer. It was concluded that the level of cfDNA is significantly increased in breast cancer patients and can be utilized as a diagnostic biomarker.

Evaluation of sub-acute and sub-chronic toxicity of aqueous extract of Coptosapelta flavescens Korth. in a Swiss albino mice model

Coptosapelta flavescens Korth. is one of the medicinal plants used as a traditional medicine in Vietnam for a long time. However, few documents proved its safety for a long time. Therefore, the study aimed to determine the toxicity effects of the aqueous extract of C. flavescens by determining its effects after subchronic oral administration in Swiss albino mice. The toxicity of C. flavescens extract was tested at doses of 400 and 1200 mg/kg, respectively, over 30 and 60 days on an in vivo model. Animal weight, behavior, and condition changes were monitored throughout the process. At the end of the observation periods, hematological indices and histopathological features of the animal specimens were analyzed. The administration of C. flavescens extract at doses of 400 and 1200 mg/kg caused a weight difference in male mice after 30 days and in both sexes after 60 days of administration compared to the control group. There were no significant changes in hematological parameters and biochemical indexes of the liver and kidney compared with the control group. The histological structure of the liver showed changes when treated with C. flavescens at both doses after 60 days, whereas the histological structure of the kidneys exhibited differences only at the dose of 400 mg/kg. Overall, the findings of this study indicate that Coptosapelta flavescens Korth. is unlikely to have subacute and subchronic oral toxicity. However, there are some minor effects on the liver and kidneys.

Hematological changes in descendants of animals irradiated in different doses

An urgent problem today is not only the study of changes in the stability of the genome of somatic cells, the clarification of the mechanisms of its destabilization under the influence of a complex of environmental factors, including radiation, but also the study of the possibility of hereditary transmission of these changes. In the modern experimental and clinical medicine, the most important problem is the harmful effect of ionizing radiation on the descendants of irradiated parents and the specifics of the effect of radiation on the developing organism. An important aspect of the problem of long-term post-radiation effects is the state of reproductive function and health of the descendants of the irradiated population, due to the physiological characteristics inherent to the mother and child - high sensitivity to the action of ionizing radiation, the consequences of which may manifest after a long period of imaginary well-being. The purpose of the work is to investigate the dynamics of body weight and hematological indiexes in the descendants of intact sexually mature animals and descendants born to animals irradiated at different doses, which were exposed to radiation at a dose of 1.0 Gy. The authors revealed that in descendants born to animals irradiated at different doses, which were exposed to radiation at a dose of 1.0 Gy, it was established that by the 30th day after irradiation at a dose of 1.0 Gy, the general condition of pup rats born from animals irradiated at a dose of 0.5 Gy and exposed to irradiation at a dose of 1.0 Gy is satisfactory against the background of an insignificant decrease in the body weight. This also applies to pup rats born to animals irradiated at a dose of 1.0 Gy, whose general condition slightly improves compared to the previous period of the study. The data obtained showed in the peripheral blood after 1 day in the descendants born to animals irradiated at a dose of 0.5 Gy, after irradiation at a dose of 1.0 Gy, a reduced content of hemoglobin and erythrocytes against the background of an increase in the content of platelets, leukocytes, lymphocytes and reticulocytes in comparison with non-irradiated animals, which was maintained throughout the experiment. Pronounced changes in hematological parameters were observed in the descendants born to animals irradiated at a dose of 1.0 Gy, which were exposed to total γ-irradiation at a dose of 1.0 Gy. The authors suppose their data are in favour of the pronounced adaptationof organisms’ regulatiory systems to ionizing irradiation effect that, firstly, outline the adaptative physiologcal mechanisms and, secondly, show the main launches of pathophysiologcial mechamisns in case of irradiation-induced hematological changes.

Impact of Imatinib on reducing the painful crisis in patients with sickle cell disease

Sickle cell disease (SCD) is a common hemoglobinopathy worldwide that causes painful crises and hospitalization of patients. These attacks decrease survival and cause chronic end-organ damage in these patients. For this reason, finding new treatment approaches could be helpful. In this study, Imatinib was applied as a mast cell inhibitor to reduce pain crises in these patients. Seven patients resistant to hydroxyurea and folic acid treatment and who had at least four painful crises per year with hospitalization were enrolled in this study with treatment with Imatinib (100 mg, twice daily). Subsequently, the number and duration of hospitalizations, analgesic requirement, the severity of chronic pain, and changes in the hematological parameters of these patients were evaluated before and after the treatment. The data showed that the total number of hospitalizations and the entire duration of hospitalizations were reduced 16 times after treatment with Imatinib, without apparent changes in hematological parameters. Also, the demand for pethidine, tramadol, and nonsteroidal anti-inflammatory drugs (NSAIDs) was reduced in all patients. The average reduction in chronic pain was over 70%. This study demonstrates that treatment with Imatinib in patients with SCD or sickle cell anemia (SCA) may be a suitable therapeutic option for reducing painful crises.