Hematological Parameters Research Articles

Ethanol extract of Ziziphus nummularia ameliorates formaldehyde-induced arthritis in rats by regulating oxidative stress biomarkers and haematological profile.

Rheumatoid arthritis is an autoimmune inflammatory disorder that mainly affects bone and cartilage architecture. The continuous use of NSAIDs and DMARDs is associated with severe toxic effects. Therefore, the current study was designed to scrutinize herb-based therapy for the treatment of RA. To evaluate the anti-arthritic activity of ethanol extract of Ziziphus nummularia using formaldehyde-induced arthritic model in rats and elucidate the possible mechanism for anti-arthritic activity. Anti-arthritic activity of ETZN was studied at three oral doses, i.e., 200, 400, and 600mg/kg. Selected doses were studied using various clinical parameters viz. paw volume, inflammatory index, motility test, stair test, anti-nociceptive efficacy, walking track analysis, and motor activity) from day 1 to day 10. On the last day, the animals were killed for the evaluation of hematological parameters, oxidative stress biomarkers, and histological and radiographic studies of the hind paw. Treatment with ETZN 400mg/kg and 600mg/kg markedly elicited a significant reduction in paw volume, inflammatory index, and nociceptive action compared to diseased animals. Furthermore, the anti-inflammatory activity was confirmed by increased latency of pain threshold in thermal and mechanical algesia models. The anti-arthritic activity is mainly attributed to a reduction in oxidative stress biomarkers as well as restoration of haematological profile in treated animals when compared to diseased animals. Lastly, the anti-arthritic potential was confirmed by histological and radiological analysis which revealed a marked reduction in inflammatory cells and bone destruction as compared to diseased animals. The study revealed that ETZN exhibits significant anti-arthritic activity via modulation of oxidative stress biomarkers, restoration of hematological profile, and reduction in bone erosion.

Evaluation of hematological inflammatory parameters in patients with palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disease of ill-defined etiopathology. Recent studies have proposed complete blood count-based hematological parameters, such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR), as biomarkers to monitor disease status in many inflammatory diseases. This study aimed to analyze for the first time the clinical significance of hematological parameters, including NLR, monocyte/lymphocyte ratio (MLR), PLR, mean platelet volume (MPV), plateletcrit (PCT), and pan-immune-inflammation value (PIV) in PPP patients. We retrospectively investigated the clinical and laboratory data of 237 patients with PPP and 250 sex-age-matched healthy controls (HCs). Hematological parameters were compared between patients with PPP and HCs. The correlations between these parameters and disease severity, as well as treatment response, were analyzed. NLR, MLR, MPV, PCT, and PIV values were significantly higher in PPP patients than in HCs. But in receiver-operating characteristic analyses, only monocyte count (Youden Index = 0.53), PCT (Youden Index = 0.65), and PIV (Youden Index = 0.52) performed relatively accurate distinguishment between moderate-to-severe cases and mild cases. PCT and PIV values were significantly correlated with disease severity. After treatment, both PIV and PCT values decreased significantly in the responder group but not in the non-responder group. Hematological parameters altered significantly in PPP patients. PCT and PIV can be used as simple and inexpensive biomarkers for systemic inflammation in PPP patients.

Ozone therapy by rectal insufflation in dogs: safety and oxidative stress - a randomized cross-over study.

Ozone therapy acts in the body inducing controlled oxidative stress, thereby improving the antioxidant, immune and circulatory responses. However, very little is known about how this therapy affects oxidative stress indicators in dogs. We aimed to assess the clinical, hematological, biochemical and oxidative stress parameters of healthy dogs subjected to ozone therapy and oxygen therapy by rectal insufflation. Ten healthy dogs were allocated into three experimental groups in a cross-over design: control, without intervention; ozone, which received 100µg of O3/kg through rectal insufflation; and oxygen, which received an ozone-equivalent volume of medicinal O2 through rectal insufflation. Dogs received four applications weekly and were followed up until the seventh week. Ozone therapy significantly increased the weight, mean corpuscular volume and mean platelet volume and decreased total cholesterol of treated dogs. Regarding oxidative stress, ozone therapy reduced total antioxidant capacity by ferric reduction (TAC-FRAP) in D7 compared with baseline and the control, significantly increased total antioxidant capacity by cupric reduction (TAC-CUPRAC) in D42 and D49 compared with the control group, caused an increase in uric acid compared with the oxygen group and decreased lipid peroxidation on D21 compared with the control group. In conclusion, ozone therapy through rectal insufflation causes transient oxidative stress followed by an antioxidant response and discreetly interferes with a few clinical, hematological and biochemical variables in healthy dogs, although variables still remained within the reference ranges for the species, thus proving the safety of the therapy. Furthermore, oxygen therapy causes oxidative stress without inducing a subsequent antioxidant response.

Comprehensive analysis of the clinical manifestations and hematological parameters associated with secondary immune thrombocytopenia in patients with primary Sjögren syndrome: An observational study.

Primary Sjögren Syndrome (pSS) is a chronic autoimmune disease that primarily affects exocrine glands and can lead to various extraglandular manifestations, including secondary immune thrombocytopenia (ITP). Understanding the clinical and hematological differences in pSS patients with and without secondary ITP is crucial for improved patient management and treatment strategies. This retrospective study, conducted from January 2020 to December 2023, involved a cohort of pSS patients, dividing them into 2 groups: those with secondary ITP and those without. Patients were evaluated using the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren Syndrome Patient-Reported Index (ESSPRI), Health Assessment Questionnaire, and other hematological parameters. Inclusion criteria were based on the American-European Consensus Group or ACR/EULAR classification criteria for pSS. Exclusion criteria included other autoimmune or hematological disorders, prior splenectomy, recent blood transfusions, and lack of informed consent. Statistical analysis was performed using SPSS software, with various tests applied to analyze the data, including logistic regression to identify risk factors for secondary ITP. Significant differences were noted in fatigue, lymphadenopathy, arthritis, mean age, and ESSDAI scores between the secondary ITP and non-secondary ITP groups. Patients with secondary ITP exhibited higher platelet counts, more prevalent lymphopenia, higher immunoglobulin G (IgG) levels, lower complement 3 levels, and reduced white blood cell and hemoglobin levels. Logistic regression analysis identified lymphadenopathy as a risk factor and arthritis as a protective factor for the development of secondary ITP. The study reveals distinct clinical and hematological characteristics in pSS patients with secondary ITP, suggesting a higher disease activity in this subset. These findings underscore the need for further exploration of these associations to develop more precise treatment approaches for pSS, focusing on preventing secondary ITP and improving patient outcomes.

Challenges in the diagnosis and management of autoimmune hemolytic anemia: A case-based approach. Experience from a tertiary care hospital in the Haryana region.

Autoimmune hemolytic anemia (AIHA) is a rare immune disorder which occurs when antibodies are directed against self red blood cells (RBCs) leading to hemolysis. AIHA is widely classified as warm autoimmune hemolytic anemia, cold agglutinin syndrome, mixed AIHA, paroxysmal cold hemoglobinuria and rarely drug induced AIHA. The pathogenesis of AIHA is complex interplay between genetic predisposition, immune dysregulation and enviornmental triggers. A direct antiglobulin test can be used to assess the immunological origin of the hemolysis in order to diagnose AIHA after identifying laboratory and clinical symptoms of hemolysis. The objective is to understand underlying mechanism in AIHAs, and usage of targeted therapies to modulate specific components of the immune response. We are hereby presenting a case series of 11 clinically suspected cases of AIHA in collaboration with their clinical features, immuno-hematological and other laboratory parameters, Flow cytometric analysis of lymphocyte subset in relevant cases, underlying etiology as well as serological subtype are also included. Majority of the patients were categorized as secondary AIHA (7/11, 63.63%). Out of 11 cases 7 were serologically subtyped as warm AIHA (7/11, 63.63%) ,2 cases were DaaT negative AIHA (2/11;18.18%), 2 cases were characterized as mixed AIHA subtype (2/11, 18.18%). Accurate subtyping of AIHA requires a systematic immunohematological approach coupled with comprehensive evaluations of clinical, hematological, and biochemical parameters.

Association of neutrophil-lymphocyte ratio with all-cause and cardiovascular mortality in US adults with diabetes and prediabetes: a prospective cohort study

BackgroundThe neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status.MethodsData were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors.ResultsOver a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19–1.58) for all-cause mortality and 1.63 (95% CI, 1.29–2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03–1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08–2.04) remained statistically significant (both p-values for trend < 0.05) in prediabetes subjects. The 10-year cumulative survival probability was determined to be 70.34%, 84.65% for all-cause events, and 86.21%, 94.54% for cardiovascular events in top NLR tertile of diabetes and prediabetes individuals, respectively. Furthermore, each incremental unit in the absolute value of NLR was associated with a 16%, 12% increase in all-cause mortality and a 25%, 24% increase in cardiovascular mortality among diabetes and prediabetes individuals, respectively.ConclusionsThe findings of this prospective cohort study conducted in the US indicate a positive association of elevated NLR levels with heightened risks of overall and cardiovascular mortality among adults with diabetes and prediabetes. However, potential confounding factors for NLR and the challenge of monitoring NLR’s fluctuations over time should be further focused.

Anti-inflammatory, anti-oxidant and anti-ulcer activities of aqueous lyophilizate of Markhamia lutea (Bignoniaceae)

Abstract Objectives This work was carried out with a view to determining the antioxidant, anti-inflammatory and anti-ulcer properties of the aqueous lyophilized extract of Markhamia lutea. Methods In vitro proteinases inhibition, albumin denaturation, hemolysis of red blood cells by heat, inhibition of the proton pump H+/K+ATPase, FRAP (Ferric reducing antioxidant power) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays were performed. In vivo, cold water immersion-induced ulceration and methylene blue-induced ulceration was used to determine the anti-ulcer properties of the lyophilizate (100, 200 and 300 mg/kg). Results In vitro, the lyophilizate (400 μg/mL) significantly inhibited protein denaturation (66.65 %), hemolysis of red blood cells (56.54 %), proteinase activity (69.22 %); then the IC50 was 26.31 μg/mL on proton pump activity. It has also developed a strong ferric reducing antioxidant power (EC50=52.96 mmol FeSO4/g) as well as free radicals scavenging activity (EC50=22.38 μg/mL). In vivo, the aqueous lyophilizate (200 and 300 mg/kg) protected the gastric mucosa (70.68 and 79.00 % protection respectively) and reduced (p&lt;0.05) acetylcholine, calcium and corticosterone concentrations. A decrease in malondialdehyde level, an increased glutathione level and an increased in catalase and SOD activities were recorded. In the methylene blue test, it significantly increased gastric fluid pH, while reducing gastric volume and improving hematological parameters in ulcer animals. In addition, the histological sections show that the aqueous lyophilizate of M. lutea protected the gastric mucosa from the deleterious effects of stress. Conclusions The aqueous lyophilizate of M. lutea has anti-ulcer properties thanks to its anti-inflammatory, antioxidant and anti-secretory properties.

The Response of the Amputee Athlete Heart to Chronic Core Exercise: A Study on Hematological and Biochemical Parameters, and N-Terminal Pro Brain Natriuretic Peptide

Background and Objectives: mortality and morbidity due to cardiovascular causes are frequently experienced in amputees. Research on the effects of chronic exercise on biomarkers and cardiac damage indicators in these individuals is limited. The aim of this study was to investigate the effects of a core training program on brain natriuretic-related peptide, as well as hematological and biochemical parameters in amputee soccer players. Materials and Methods: The participants were randomly allocated to the following two groups: a core exercise group (CEG) and a control group (CG). While the CG continued routine soccer training, the CEG group was included in a core exercise program different from this group. During the study, routine hemogram parameters of the participants, various biochemical markers, and the concentration of brain natriuretic-related peptide (NT-pro-BNP) were analyzed. Results: after the training period, notable improvements in various hematological parameters were observed in both groups. In the CEG, there were significant enhancements in red blood cell count (RBC), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH) values. Similarly, the CG also showed substantial improvements in RBC, HCT, mean corpuscular volume (MCV), MCHC, MCH, red cell distribution width-standard deviation (RDW-SD), platelet-to-lymphocyte ratio (PLCR), mean platelet volume (MPV), and platelet distribution width (PDW). Moreover, in the CEG, serum triglycerides (TG) and maximal oxygen uptake (MaxVO2) exhibited significant increases. Conversely, TG levels decreased in the CG, while high-density lipoprotein (HDL), low-density lipoprotein (LDL), and MaxVO2 levels demonstrated substantial elevations. Notably, the N-terminal pro-brain natriuretic peptide (BNP) levels did not undergo significant changes in either the CEG or the CG following the core exercise program (p &gt; 0.05). However, in the CEG, a meaningful positive correlation was observed between NT-pro-BNP and creatine kinase (CK) levels before and after the core exercise program. Conclusions: the findings emphasized the potential benefits of core training in enhancing specific physiological aspects, such as erythrocyte-related parameters and lipid metabolism, as well as aerobic capacity. Furthermore, the observed correlation between NT-pro-BNP and CK levels in the CEG provides intriguing insights into the unique physiological adaptations of amputee athletes.

Long-Term Treatment of Gaucher Disease with Velaglucerase Alfa in ERT-Naïve Patients from the Gaucher Outcome Survey (GOS) Registry

Background: Gaucher disease (GD) is a rare, autosomal, recessive condition characterized by hepatosplenomegaly, thrombocytopenia, anemia, and bone abnormalities, often requiring life-long treatment. Velaglucerase alfa has improved hematologic and visceral parameters in clinical trials; however, limited long-term efficacy and safety data are available. Methods: The Gaucher Outcome Survey (GOS), a structured and validated international registry for patients with confirmed GD, provides an opportunity to evaluate long-term data from patients receiving velaglucerase alfa. Results: This analysis included 376 treatment-naïve children and adults with GD enrolled in GOS, including 20 with type 3 GD, who initiated velaglucerase alfa through participation in clinical trials or as part of their clinical management and continued treatment for a mean (range) time of 6.6 (0.003–18.6) years. Initial improvements in hematologic and visceral parameters and the biomarkers glucosylsphingosine (lyso-GL1) and chitotriosidase were observed after one year of treatment and were maintained throughout the follow-up period. Of 129 (34.3%) patients who developed adverse events during the follow-up period, events were considered related to treatment in 33 (8.8%). None led to treatment discontinuation. There were 21 deaths overall, none of which were considered related to treatment. Conclusions: This analysis of data from the GOS registry supports the safety and efficacy of velaglucerase alfa in patients with GD.

Development and Internal Validation of Nomograms for Survival of Advanced Epithelial Ovarian Cancer Based on Established Prognostic Factors and Hematologic Parameters

Objective: To assess the association between pretreatment thrombocytosis, anemia, and leukocytosis and overall survival (OS) of advanced-stage EOC. Furthermore, to develop nomograms using established prognostic factors and pretreatment hematologic parameters to predict the OS of advanced EOC patients. Methods: Advanced-stage EOC patients treated between January 1996 and January 2010 in eastern Netherlands were included. Survival outcomes were compared between patients with and without pretreatment thrombocytosis (≥450,000 platelets/µL), anemia (hemoglobin level of &lt;7.5 mmol/L), or leukocytosis (≥11.0 × 109 leukocytes/L). Three nomograms (for ≤3-, ≥5-, and ≥10-year OS) were developed. Candidate predictors were fitted into multivariable logistic regression models. Multiple imputation was conducted. Model performance was assessed on calibration, discrimination, and Brier scores. Bootstrap validation was used to correct for model optimism. Results: A total of 773 advanced-stage (i.e., FIGO stages IIB–IV) EOC patients were included. The median [interquartile range, IQR] OS was 2.3 [1.3–4.2] and 3.0 [1.4–7.0] years for patients with and without pretreatment thrombocytosis (p &lt; 0.01). The median OS was not notably different for patients with and without pretreatment leukocytosis (p = 0.58) or patients with and without pretreatment anemia (p = 0.07). The final nomograms comprised established predictors with either pretreatment leukocyte or platelet count. The ≥5- and ≥10-year OS models demonstrated good calibration and adequate discrimination with optimism-corrected c-indices [95%-CI] of 0.76 [0.72–0.80] and 0.78 [0.73–0.83], respectively. The ≤3-year OS model demonstrated suboptimal performance with an optimism-corrected c-index of 0.71 [0.66–0.75]. Conclusions: Pretreatment thrombocytosis is associated with poorer EOC survival. Two well-performing models predictive of ≥5-year and ≥10-year OS in advanced-stage EOC were developed and internally validated.

The significance of inflammatory markers in prognosticating the effectiveness and safety of immunotherapy in conjunction with chemotherapy during the primary intervention of advanced non-small cell lung carcinoma

ObjectiveThe aim of this study is to scrutinize the prognostic significance of inflammatory biomarkers concerning the effectiveness and safety of combining PD-1 inhibition with chemotherapy in the management of advanced NSCLC. MethodsWe conducted a retrospective analysis involving 206 NSCLC patients who received treatment at Qingdao Municipal Hospital. The study encompassed the acquisition of baseline clinical attributes and hematological parameters of these patients. The optimal threshold values for PLT and NLR were ascertained based on pre-treatment evaluations, with a particular focus on their association with PFS. Variables linked to PFS were subject to scrutiny through Kaplan-Meier analysis and logistic regression. The Receiver Operating Characteristic (ROC) curve served as the means to determine the ideal cut-off values for categorizing levels of inflammatory markers into high and low classifications. We employed Chi-square tests to evaluate the relationship between elevated and reduced baseline levels of inflammatory markers and irAE. ResultsKaplan-Meier analysis disclosed that patients in the low baseline PLT group and the low NLR group exhibited a substantially more favorable prognosis in contrast to their counterparts in the high baseline PLT and high NLR groups. Multivariate analysis indicated that diminished baseline PLT and NLR levels before treatment independently foretell extended PFS. Chi-square analysis underscored a substantial correlation between baseline WBC, NEUT, LYMPH, MONO, and NLR levels and irAE. ConclusionSubdued baseline PLT and NLR levels may serve as indicators of a more auspicious prognosis in patients contending with advanced NSCLC undergoing the combination of PD-1 inhibition and chemotherapy. Elevated baseline levels of inflammatory markers antedating PD-1 therapy in advanced NSCLC may be intimately interrelated with the occurrence of irAE.

Evaluation of the immune system status and hematological dyscrasias, among amphetamine and cannabis abusers at Eradah Hospital in Qassim, Saudi Arabia

This cross-sectional study aims to evaluate the immune system status and hematological disturbances among individuals who abuse amphetamines and cannabis. Substance abuse, particularly of amphetamines and cannabis, has been associated with various adverse effects on the body, including potential impacts on the immune system and hematological parameters. However, limited research has been conducted to comprehensively assess these effects in a cross-sectional design. Additionally, fungal infections are on the rise internationally, and immune-compromised people are particularly susceptible. The study will recruit a sample of amphetamine and cannabis abusers (n = 50) at the Eradah Hospital in the Qassim Region of Buraydah and assess their sociodemographic and biochemical variables, including blood indices and differential WBC indices, liver, and kidney profiles. Additionally, 50 sputum samples in total were cultured for testing for fungus infections. To obtain the descriptive statistics, the data was imported into Microsoft Excel and subjected to statistical analysis using SPSS 22.0. Amphetamine and cannabis abuser's sociodemographic variables analysis observed that the majority (52%) were aged 18–30, with 56% in secondary school. Unemployment was a significant issue, and most had no other health issues. The majority (50%) had 5–10 years of abuse, while 32% had less than 5 years, and only 18% had been drug abusers for more than 10 years. There were significant changes (p < 0.001) in all different leukocyte blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Furthermore, a microscopic examination of blood films from individuals who misuse the combination of the medications "amphetamine and cannabis" reveals hazardous alterations in Neutrophils. Out of 50, 35 sputum samples showed positive growth on Sabouraud dextrose agar (SDA) with chloramphenicol antibiotic, indicating a unicellular fungal growth. The present study explores the immune system and hematological disturbances linked to amphetamine and cannabis abuse, providing insights into health risks and targeted interventions. The findings complement previous research on drug users' hematological abnormalities, particularly in white blood cells. Routine hematological tests help identify alterations in homeostatic conditions, improving patient knowledge and preventing major issues. Further research is needed on multi-drug abuse prevention, early detection, and intervention. The cross-sectional design allows for a snapshot of the immune system and hematological status among abusers, laying the groundwork for future longitudinal studies. Key Words: Drug Effect, Immunity, Epidemiology, Oxidative Stress, Inflammation.

Anti-arthritic and immunomodulatory efficacy of Micromeria biflora Benth extract and its fractions in rats by restoring oxidative stress, metalloproteinases, pro-inflammatory and anti-inflammatory cytokines network.

Micromeria biflora (M.B) Benth has proven anti-inflammatory efficacy, thereby, the goal of the current investigation was to assess the anti-arthritic potential of M.B ethanolic extract and fractions as well as to investigate the likely mechanism of action. The effectiveness of M.B against acute arthritic manifestations was assessed using an arthritic model prompted by formaldehyde, whereas a chronic model was developed using an adjuvant called Complete Freund's in Sprague-Dawley rats. Weekly evaluations were conducted for parameters involving paw volume, body weight, and arthritic score; at the completion of the CFA model, hematological, biochemical and oxidative stress parameters as well as the level of various mediators (PGE2, IL-1β, TNFα, IL6, MMP2, 3, 9, VEGF, NF-ĸB, IL-10, and IL-4) were evaluated. The results demonstrated the plant's ability to treat arthritis by showing a significant decrease in paw volume, arthritic score, and histological characteristics. The levels of NF-ĸB, MMP2, 3, 9, IL6, IL1β, TNFα, and VEGF were all significantly reduced after treatment with plant extract and fractions. Plant extract and its fractions substantially preserved body weight loss, oxidative stress markers and levels of IL-4 and 1L-10. PGE2 levels were also shown to be reduced in the treatment groups, supporting the M.B immunomodulatory ability. Hematological and biochemical indicators were also normalized after M.B administration. Outcomes of the study validated the anti-arthritic and immunomodulatory attributes of M.B probably through modulating oxidative stress, inflammatory, pro-inflammatory and anti-inflammatory biomarkers.

Impact of Iron Supplementation on Children with Severe Attention Deficit Hyperactive Disorder- A Randomized Clinical Trial

Background: Iron acts as a risk factor and psychostimulant modulator in treatment of ADHD with iron deficiency anemia. Objective: To see the impact of iron supplementation on severe ADHD children. Materials and Methods: This randomized controlled trial conducted in the OPD, Pediatric Neurology from July 2019 to January 2020; NINS 50 children of severe ADHD with iron deficiency were enrolled. Participants were randomized into group A (25 cases) given a combination of Methylphenidate and iron, and group B (25 cases) given Methylphenidate alone for 3 months. Conner’s rating scale, CBC and serum ferritin was evaluated after one and three months, severity was compared between treatment groups. Analysis of data was done by SPSS version of 22.0. Result: Combined ADHD, poor academic performance, poor appetite, frequent infection was common features of IDA among the cases. All hematological parameters were increased from baseline to 1 month and 3 months follow up in all cases but significantly improved in Iron receiving groups. the severity of T scores of ADHD index were decreased at 1 month (p=0.047) and 3 months (p= 0.026) after intervention. Conclusion: This study concluded that iron supplementation along with psychostimulant found better response in severe ADHD children BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 48-53

EVALUATION OF ACUTE AND SUB-ACUTE TOXICITY OF METHANOLIC LEAF EXTRACT OF BAMBUSA VULGARIS ON MALE WISTAR RATS

Objectives: The study aims to evaluate the potential toxicity of methanolic extract of leaves of Bambusa vulgaris in male Wistar rats. Methods: The methanolic extract was prepared for acute and sub-acute toxicity to determine the lethal dose. During the acute toxicity study, male rats were orally administered with leaf extracts at single doses of 100, 500,800, and 2000 mg/kg according to OECD Guidelines 425 for 14 days. Sub-acute toxicity dose at 200, 400, and 800 mg/kg was studied by daily dosing on male rats for 30 days. Results: The acute toxicity study revealed no lethal effects and behavioral signs of toxicity at the tested doses indicating that LD50 is &lt;2000 mg/kg. In a sub-acute study, non-significant changes in the body weight (p&lt;0.05), body weight gain percentage (p&lt;0.05) food intake (p&lt;0.05), and relative organ weight percentage (p&lt;0.05), and hematological parameters (p&lt;0.05) of the rats were observed. A significant (p&lt;0.05) increase in ALT level was observed dose at 800 mg/kg. Histopathological analysis showed mild cell distortion in the liver and kidney in male rats treated at 800 mg/kg of extract. Conclusion: Our study suggests that oral administration of methanolic leaf extract Bambusa vulgais is safe. However, a dose of 800 mg/kg may be toxic for the liver and kidney.

AN ASSOCIATION OF METABOLIC SYNDROME WITH NONALCOHOLIC FATTY LIVER DISEASE

Objectives: Nonalcoholic fatty liver disease is strongly linked with hepatic fatty infiltration and visceral adiposity, therefore, being a cause and a result of metabolic syndrome. The objective of the study is to find an association of metabolic syndrome (MetS) with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 342 subjects from which 86 NAFLD 86 control were suitably selected for study duration of 1 year. Diagnosis of nonalcoholic fatty liver disease was done by liver imaging and based on liver enzymes. MetS assessment was done by the national cholesterol education program adult treatment panel III (NCEP ATP III) criteria. Estimation of all biochemical and hematological parameters and liver enzymes was done following standard guidelines. Mean comparison of quantitative data in different groups was analyzed with one-way analysis of variance. Results: There were significant high levels of body mass index, waist circumference, and lipid profiles in NAFLD patients in comparison to control population (p&lt;0.001). According to the NCEP ATP III criteria, 59.3% of NAFLD were present with MetS where risk estimate was significant (odds ratio=2.15). Conclusion: This study suggests that there is an increased in all the components of MetS and gross changes in biochemical markers in cases of NAFLD. Therefore, whenever MetS factors are met in the clinical checkups, patients must be diagnosed for NAFLD by imaging (fatty liver).

ACUTE ORAL TOXICITY OF TOFACITINIB CITRATE IN WISTAR RATS: IMPLICATIONS FOR NOVEL MOUTH DISSOLVING FORMULATIONS

Objective: Tofacitinib citrate is a commonly used therapeutic agent for various diseases. Mouth-dissolving formulations provide potential benefits for patient compliance. This study aims to evaluate the acute oral toxicity of tofacitinib citrate in these formulations to ensure their safety and efficacy. Methods: This study aimed to assess the acute oral toxicity of tofacitinib citrate in mouth-dissolving formulations and evaluate its effects on food and water consumption, hematological and biochemical parameters, and organ histopathology. Male and female Wistar rats were divided into four groups. The control group received distilled water, while the treated groups were orally administered tofacitinib citrate at 5 mg/kg, 100 mg/kg, and 300 mg/kg. Observations were made over 14 d, assessing general appearance, behavior, food and water consumption, and mortality. Hematological and biochemical analyses and histopathological examinations were conducted on vital organs. Results: In acute toxicity studies, Wistar rats showed no toxicity at up to 300 mg/kg tofacitinib citrate. Compared to controls, food/water intake and hematological, biochemical, and histopathological parameters of major organs remained unchanged, indicating no systemic effects and affirming the compound's safety in mouth-dissolving formulations. Conclusion: Tofacitinib citrate in mouth-dissolving formulations demonstrated a favorable safety profile with no acute oral toxicity. Normal consumption, unchanged parameters, and no organ abnormalities support its safety. Further investigation is required to assess chronic toxicity and long-term safety.

Launaea fragilis extract attenuated arthritis in rats through modulation of IL-1β, TNF-α, IL-6, NF-κB, COX-2, IL-4, and IL-10.

Launaea fragilis (Asso) Pau is a Cholistan desert medicinal plant. Launaea species are used as traditional remedies against various inflammatory conditions. The current research was designed to evaluate the anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of L. fragilis (Et-LF). The plant extract was prepared by triple maceration. GC-MS screening explored the presence of various bioactive phytoconstituents including n-tetracosanol-1, 1-heptacosanol, and n-hexadecanoic acid. DPPH assay demonstrated the antioxidant potential of Et-LF. Safety profile data indicated that Et-LF was safe up to the oral dose of 5000mg/kg in female rats. Anti-nociceptive activity of Et-LF was assessed in hot plate method and acetic acid-induced writhing model and the results suggested that Et-LF had significant analgesic effects in both animal models. Carrageenan, histamine, and serotonin-induced edema models were used to estimate the anti-inflammatory effects of Et-LF and were found to prevent paw edema development dose dependently. The anti-arthritic effect of Et-LF was estimated in CFA-induced arthritic rat model. Treatment with Et-LF 125, 250, 500 and flurbiprofen (FP) 10mg/kg/day significantly attenuated the paw edema, reversed the reduced body weight, and restored the altered hematological parameters in arthritic rats. Gene expression studies revealed the significant downregulation of IL-1β, TNF-α, IL-6, NF‑κB, and COX-2, and upregulation of IL-4 and IL-10 in arthritic rats treated with various doses of plant extract. Histological evaluation of ankle joints showed that Et-LF mitigated pannus formation, infiltration of inflammatory cells, and fibrous connective tissue formation in the diseased rats. Thereof, it may be concluded that the recent study demonstrated the anti-nociceptive, anti-inflammatory, and anti-arthritic effects ascribed to the signifying presence of phytoconstituents in L. fragilis.

Pro- and anti-inflammatory cytokines signatures at different severity of dengue infection

ABSTRACT Context: Dengue disease severity and progression are determined by the host immune response, with both pro- and anti-inflammatory cytokines are key mediators. Aims: To study pro- and anti-inflammatory cytokines across dengue severity and as a biomarker for predicting severe dengue infection. Settings and Design: Hospital-based cross-sectional study was conducted on 125 dengue-positive subjects across the 5-60 years age group of either gender in 2022. Methods and Materials: Haematological parameters and blood samples were drawn to measure cytokines IL6, IL-10 and TNF alpha using the ELISA technique. Statistical Analysis: One-way ANOVA and the Kruskal − Wallis test were used to compare the dependent variables across categories of the dengue spectrum. Receiver operating characteristic curve was drawn to calculate the predictability of the cytokines as a predictor of severe dengue. A P &lt; 0.05 was considered significant. Results: 34.4% of cases had severe dengue infection with 53.2% of severe cases reported in &gt;40 years of age. Only IL-6 levels significantly increased (P &lt; 0.01) across the spectrum of dengue infection across age groups &gt;20 years with a consistent and significant fall in platelet levels (P &lt; 0.01). The accuracy of IL-6 to predict severe dengue was 74.4% and platelet count was 16.2%. Conclusions: Only IL-6 cytokine levels were significantly increased across the spectrum of dengue infection observed in age &gt;20 years and can significantly predict the probability of severe dengue by 74% (sensitivity 81.4%). A significant decrease in platelet values is consistent with the severity but is not a good predictor for severe dengue infection.

A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors.

We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA)in improving cancer-related fatigue (CRF) among cancer patients. This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000mg (N = 56) or placebo (N = 54) thrice daily for 9weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA). The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p < 0.001, partial η2 = 0.333). The Nuvastatic™ group significantly reduced VAS-F fatigue (F (2, 210) = 9.534, p < 0.001, partial η2 = 0.083), improved quality of life (QoL) (F (1.2, 127.48) = 34.07, p < 0.001, partial η2 = 0.243), and lowered urinary F2-IsoP concentrations (mean difference (95% CI) = 55.57 (24.84, 86.30)), t (55) = 3.624, p < 0.001, Cohen's d (95% CI) = 0.48 (0.20, 0.75)). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%). Nuvastatic™ is potentially an effective adjuvant for CRF management in solid tumor patients and worthy of further investigation in larger trials. ClinicalTrial.gov ID: NCT04546607. Study registration date (first submitted): 11-05-2020.