Basophil Levels Research Articles

First episode depression during the perinatal period is associated with atopic diseases and persistently increased eosinophil and basophil levels.

A previous diagnosis of depression is a strong predictor for perinatal depression, apart from other mental disorders, stress, and atopies. It is less clear which factors interfere if perinatal depression occurs as a first depression episode (fePND). We examined the associations with atopies and related blood parameters using data of CoLaus|PsyCoLaus. Newly occurring depression during the perinatal period but not recurrent depression was associated with a lifetime diagnosis of allergies and asthma together with persistently increased levels of basophils and eosinophils. The results imply that immune function may play a relevant role in the risk of a fePND. If confirmed and detailed, these findings could serve as the basis for designing preliminary prevention strategies by observing eosinophil and basophil levels as well as symptoms of atopic diseases before/during pregnancy.

Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective

Background: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. Methods: This study evaluates the subacute toxic effects and pharmacokinetics of 4−Fluoro MDMB−BUTINACA (4F-MDMB-BUTINACA) in adult male albino rats, administered orally for seven days at doses of 1 mg/kg, 5 mg/kg, and 15 mg/kg. The hematological, biochemical, and histopathological parameters were assessed and compared to controls. Results: The pharmacokinetics were determined using GC–MS/MS with a positive chemical ionization and granisetron as an internal standard. A histological analysis revealed inflammatory cell aggregation, congestion, hemorrhage, edema, and fibrosis in various tissues, with renal examinations showing tubule degradation, glomerular atrophy, Bowman’s space expansion, edema, and hemorrhage. The liver exhibited cellular infiltration, while cardiac muscle fibers showed myocardial fiber degradation and inflammatory cell aggregation. Biochemical assays indicated significant alterations (p < 0.05) in the serum levels of AST, ALT, ALP, GGT, total protein, albumin, triglycerides, urea, MCHC, MCV, RDW, platelets, neutrophils, eosinophils, and basophils compared to the controls. Conclusions: The validated bioanalytical method revealed rapid absorption of 4F-MDMB-BUTINACA, with a plasma half-life of 2.371 h, a volume of distribution of 2272.85 L, and a plasma clearance rate of 664.241 L/h. In conclusion, 4F-MDMB-BUTINACA is a highly toxic synthetic cannabinoid, particularly affecting the liver, kidneys, and heart.

Gender Differences in the Effects of Cadmium Exposure on Hematological Parameters in Wistar Rats

This study aims to investigate the gender dimorphism in cadmium exposure on hematological parameters in male and female Wistar rats. Twenty Wistar rats (120g-150g) were divided into four groups: male control, male cadmium-treated, female control, and female cadmium-treated. Cadmium chloride (50 mg/kg) was administered orally to the experimental groups for 45 days. Hematological parameters were analyzed using an auto hematological analyzer. Data were statistically evaluated using two-way ANOVA with significance set at p < 0.05. Cadmium exposure significantly increased white blood cell (WBC) counts in male rats compared to controls, with notable decrease in neutrophils and an increase in lymphocytes. Female rats showed significant increase in monocyte and basophil levels. Furthermore, red blood cell (RBC) parameters showed significant reductions in hemoglobin concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in female cadmium-treated rats. No significant effects were observed on platelet count or distribution width in both male and female rats. The study concluded there are gender-specific hematological alterations due to cadmium exposure in Wistar rats. These findings underscore the need for gender-specific approach in the understanding and amelioration of cadmium toxicity.

Role of Th2, Th17 and Treg Cells and relevant cytokines in pathogenesis of allergic rhinitis

ObjectiveTo explore the role of different cells and molecules in the pathogenesis of allergic rhinitis (AR) with positive Artemisia allergen by detecting their expression levels.MethodsFrom January 2021 to December 2022,200 AR patients diagnosed in the Otolaryngology Clinic of Ordos Central Hospital were selected as the AR group, and 50 healthy people who underwent physical examination in the hospital during the same period were randomly selected as the healthy control (HC) group. The levels of GATA-3mRNA, RORγtmRNA and FoxP3mRNA in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR (qRT-PCR). The proportions of Th2, Th17 and Treg cells were detected by flow cytometry. The concentrations of IL-4, IL-5, IL-17 and IL-10 in serum were detected by enzyme-linked immunosorbent assay. The differences of transcription gene level, immune cell ratio and cytokine concentration between the two groups were analyzed.ResultsThere was no difference in age and gender between the two groups. The levels of GATA-3mRNA and RORγtmRNA transcription genes in peripheral blood mononuclear cells, the percentage of Th2, Th17 and Treg immune cells, the levels of eosinophils and basophils in peripheral blood, the concentrations of IL-4, IL-5, IL-17, IL-10 cytokines and IgE in serum of AR patients were significantly higher than those in HC group (P < 0.05). IL-4 and IL-17 were positively correlated with total IgE level.ConclusionThe secretion of immune cells and cytokines in peripheral blood of AR patients is abnormal. Th2, Th17, Treg specific transcription factors and related cells and cytokines are involved in the occurrence and development of allergic rhinitis.

Is It Possible to Predict Systemic Adverse Effects in Subcutaneous Allergen Immunotherapy? Single-Center Experience

Introduction: Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects (SAEs) may occur during the SCIT. For this reason, there may be problems in the continuing treatment. In this study, we primarily aimed to determine the frequency of SAEs, the risk factors that may be associated with SAEs, and clinical and laboratory parameters that can predict systemic reactions in the patients who underwent SCIT. Second, we aimed to evaluate the reasons for discontinuing SCIT and the conditions special to Turkey. Methods: The files of 295 patients who had received SCIT were evaluated retrospectively. Results: SCIT was administered against house dust mites (HDM) in almost all patients (n: 291, 98.6%). A total of 14,357 injections were administered to 295 patients included in the study, and 47.8% (n: 141) of the patients discontinued treatment. The most common reason for discontinuing treatment was the supply problem in Turkey for immunotherapy preparations (n: 70, 49.6%). The second reason was that the injection visits were not continued regularly, even though there were no adverse effects related to the treatment (n: 44, 31.2%). SAEs were observed in 16.6% of the patients and 0.66% of the injections. SAEs were more frequent in girls, in asthmatic patients, and in moderate asthmatic patients (p = 0.005, p = 0.016, p = 0.043, respectively). Treatment was terminated in 13 patients (4.4%) due to SAEs. The most common SAE was bronchoconstriction (n: 40, 85.1%). None of our patients developed hypotension or loss of consciousness. Median blood eosinophil count and basophil count and the skin prick test diameter for Dermatophagoides farinae were observed to be significantly higher in the group with SAE (p = 0.024, p = 0.034, p = 0.045, respectively). Conclusion: Although SAE may develop in pediatric patients undergoing HDM-specific SCIT, severe reactions are rare. Girls, asthmatic patients, especially moderate asthmatic patients, and patients with high blood eosinophil and basophil levels should be monitored more carefully for the development of SAE.

The role of hematological parameters in asymptomatic and non-severe cases of Omicron variant infection

BackgroundOmicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections.MethodsHematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves.ResultsIndividuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers.ConclusionsCirculating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases.

Genetic Evidence for a Causal Relationship Between Innate Leukocytes and the Risk of Digestive System Cancers in East Asians and Europeans.

Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans. Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately. Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007). Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.

Does COVID-19 infection alter serum biochemical and hematological biomarkers in deceased dementia patients?

Abstract Objectives The elderly population is categorized as a risk group for COVID-19 infection, and dementia is the primary cause of disability in elderly individuals and affects 70 % of the elderly population. In this study, we evaluated the blood and serum biomarkers of deceased dementia patients infected by COVID-19 compared to the survived dementia and non-dementia patients. Methods Laboratory biomarkers of 11 dementia patients infected by COVID-19 have been used for this study. The five patients’ serum biochemistry and blood data were compared with the six patients who died because of COVID-19. Additionally, data from nine patients aged 85–96 infected with COVID-19 without dementia have been used to compare the difference between dementia and non-dementia individuals. Results D-dimer, C-reactive protein (CRP), glucose, blood urea nitrogen (BUN), alanine transaminase (ALT), aspartate aminotransferase (AST), troponin, procalcitonin, red cell distribution width (RDW), white blood cell (WBC), neutrophil (NEU) and %NEU levels significantly increased in the deceased dementia patients compared to the survived and non-dementia individuals. Calcium (Ca), hematocrit (HCT), red blood cells (RBC), lymphocyte (%LYM), monocyte %MONO, and basophil (%BASO) levels significantly decreased in the deceased dementia patients compared to the survived and non-dementia individuals infected by COVID-19. Conclusions Serum biochemistry and hematological biomarkers, including D-dimer, CRP, glucose, ALT, AST, BUN, troponin, procalcitonin, RDW, RBC, WBC, NEU, %NEU, Ca, HCT, %LYM, %MONO, and %BASO were significantly altered in deceased dementia patients infected by COVID-19 compared to the survived individuals.

First-episode psychiatric disorder risk from SARS-CoV-2 infection, a clinical analysis with Chinese psychiatric inpatients.

The extensive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout China in late 2022 has underscored the correlation between this virus and severe psychiatric disorders. Nevertheless, there remains a dearth of reported corresponding clinical and pathological features. Accordingly, we retrospectively reviewed the electronic medical records of psychiatric inpatients for seven days from early January 2023. Twenty-one inpatients who developed first-episode psychiatric disorders within two weeks after SARS-CoV-2 infection were recruited, while 24 uninfected the first-episode psychiatric inpatients were selected as controls. Comparative analyses of clinical manifestations, routine laboratory, and imaging examinations were performed. Our investigation revealed a 330% increase in first-episode psychiatric inpatients incidence after SARS-CoV-2 infection in 2023 compared to the preceding year without infections. Most cases exhibited psychiatric symptoms within a week of infection, resolving about two weeks with no residual symptoms after a three month. One-way ANOVA analysis between inpatients characterized by psychotic symptoms and hyperthermia was significant. Infected inpatients displayed elevated cytokine levels of interleukin-4, interleukin-8, and interferon-α, and decreased levels of eosinophils and basophils. These finding suggested that SARS-CoV-2 may contribute to the development of psychiatric disorders, likely mediated by the virus-induced inflammatory response and neuronal dysfunction in the context of psychological distress.

Causal Relationship Between Immune Cells/Cytokines and Dilated Cardiomyopathy.

To date, whether there is any causal relationship between dilated cardiomyopathy (DCM) and the changes in the levels/expression of immune cells/cytokines is still unclear. This study aimed to investigate the causal relationship between the levels of various types of immune cells/cytokines and DCM. Herein, two-sample Mendelian randomization (MR) (TSMR) using R software was conducted. Single nucleotide polymorphisms (SNPs) related to the levels of various types of immune cells/cytokines and DCM were screened based on the genome-wide association studies (GWAS) obtained from open-source databases. The TSMR was conducted using inverse variance weighted (IVW), method, MR-Egger regression, weighted median method, and simple estimator based on mode to explore the causal association between the levels of each immune cell/cytokine and DCM. Sensitivity analysis was conducted using MR-Egger regression and a leave-one-out sensitivity test. A total of 1816 SNPs related to host immune status and DCM were identified. The IVW results showed a relationship between DCM and the circulating levels of basophils/eosinophils, total eosinophils-basophils, lymphocytes, and C-reactive protein (CRP). Increased lymphocytes levels (odds ratio (OR) = 0.91, 95% confidence interval (CI): 0.84-0.97, P = 0.005) were seen as protective against DCM, whereas increased basophil (OR = 1.18, 95% CI: 1.04-1.33, P = 0.022), eosinophil (OR = 1.1, 95% CI: 1.03-1.17, P = 0.007), eosinophil-basophil (OR = 1.09, 95% CI: 1.02-1.17, P = 0.014), and CRP (OR = 1.1, 95% CI: 1.03-1.18, P = 0.013) levels were associated with an increased risk of DCM. These analyses revealed that there may be a relationship between immune cells/select cytokine status and the onset of DCM. Future studies are required to further validate these outcomes in animal models and clinical trials.

Contribution of small airway inflammation to the development of COPD

BackgroundLittle attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD.MethodsA total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO50, FeNO200, and calculated CaNOdual. Both FeNO200 and CaNOdual were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD.ResultsExhaled NO levels (FnNO, FeNO50, FeNO200, and CaNOdual) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO50, FeNO200, and CaNOdual) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO200 was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNOdual (AUC ROC = 0.707) in COPD. FeNO200 was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797–2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO50 and FeNO200.ConclusionThe complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels.

Serum vitamin D3 (25-OH vit D3) concentrations and hemogram changes in calves with enzootic pneumonia.

Enzootic pneumonia is an important disease complex associated with insufficient colostrum intake after birth, adverse environmental conditions, and stress. Vitamin D deficiency may be an important predisposing factor for this disease. This study aimed to investigate in calves with enzootic pneumonia. A total of 30 calves, aged 3-5 months, under the same care and feeding conditions were used. Groups were formed according to Clinical Respiratory Scoring as the group with mild/moderate enzootic pneumonia (n = 10), the group with severe enzootic pneumonia (n = 10), and the healthy control group (n = 10) without any disease. Blood samples were collected from the jugular vein of animals in all groups on Day 0; a complete blood count was performed, and serum vitamin D levels were measured using the Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method. Although no statistical differences were observed in total leukocyte, lymphocyte, eosinophil, basophil, hemoglobin, and hematocrit levels between groups, statistically significant differences in blood neutrophil, monocyte, and erythrocyte counts were found between the groups. Monocyte counts were statistically decreased in the mild/moderate group compared with the control group. Neutrophil counts were significantly higher in the mild/moderate and severe groups than in the control group. Erythrocyte counts were increased in the mild/moderate and severe groups compared with the control group. Vitamin D concentrations were statistically lower in the mild/moderate and severe groups than in the control group. However, no statistical differences in Vitamin D concentrations were observed between the mild/moderate and severe groups. There was a negative and significant correlation between erythrocyte counts and vitamin D concentrations (r = -0.64, P < .0001). While erythrocyte counts increased in the severe group compared with the mild/moderate group, vitamin D concentrations decreased. Also, a negative and significant correlation was observed between platelet counts and vitamin D concentrations (r = -0.74, P < .0001). The results of this study determined that serum vitamin D concentrations in calves with pneumonia were lower than those in healthy calves. Detailed studies on the etiologic and prognostic importance of low vitamin D levels in calves with enzootic pneumonia may provide valuable data for prevention and treatment.

Stratification of Kidney Transplant Recipients Into Five Subgroups Based on Temporal Disease Trajectories.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Considerable clinical research has focused on improving graft survival and an increasing number of kidney recipients die with a functioning graft. There is a need to improve patient survival and to better understand the individualized risk of comorbidities and complications. Here, we developed a method to stratify recipients into similar subgroups based on previous comorbidities and subsequently identify complications and for a subpopulation, laboratory test values associated with survival. First, we identified significant disease patterns based on all hospital diagnoses from the Danish National Patient Registry for 5752 kidney transplant recipients from 1977 to 2018. Using hierarchical clustering, these longitudinal patterns of diseases segregate into 3 main clusters of glomerulonephritis, hypertension, and diabetes. As some recipients are diagnosed with diseases from >1 cluster, recipients are further stratified into 5 more fine-grained trajectory subgroups for which survival, stratified complication patterns as well as laboratory test values are analyzed. The study replicated known associations indicating that diabetes and low levels of albumin are associated with worse survival when investigating all recipients. However, stratification of recipients by trajectory subgroup showed additional associations. For recipients with glomerulonephritis, higher levels of basophils are significantly associated with poor survival, and these patients are more often diagnosed with bacterial infections. Additional associations were also found. This study demonstrates that disease trajectories can confirm known comorbidities and furthermore stratify kidney transplant recipients into clinical subgroups in which we can characterize stratified risk factors. We hope to motivate future studies to stratify recipients into more fine-grained, homogenous subgroups to better discover associations relevant for the individual patient and thereby enable more personalized disease-management and improve long-term outcomes and survival.

Abstract A085: First-in-class humanized antibody targeting alternatively spliced tissue factor augments anti-metastatic efficacy of chemotherapy in a preclinical model of pancreatic ductal adenocarcinoma

Abstract Introduction. Alternatively spliced tissue factor (asTF) promotes progression of pancreatic ductal adenocarcinoma (PDAC) via activating b1-integrins on PDAC cell surfaces. hRabMab1, a humanized inhibitory anti-asTF antibody we recently developed, can suppress PDAC primary tumor growth as a single agent. Whether hRabMab1 has the potential to suppress metastases in PDAC is unknown. Aim. To test hRabMab1’s ability to suppress metastatic spread in combination with chemotherapy. Methods. asTF-proficient, KRAS G12V-mutant human PDAC cell line PaCa44 yields aggressive primary orthotopic tumors that spread spontaneously to the relevant anatomical sites, accompanied by severe leukocytosis. 5 × 105 PaCa44 cells were implanted into the pancreata of NOD-SCID mice (n=40). 10 days post-implantation, mice were randomized into 4 cohorts: vehicle; hRabMab1 administered IV at 18 mg/kg; gemcitabine/paclitaxel (gem/paclitaxel, 50 mg/kg/3 mg/kg); and hRabMab1+gem/paclitaxel. Results. Post-mortem analysis of tumor tissue and luciferase imaging of the abdominal cavity showed that gem/paclitaxel alone reduced primary tumor volume, but not metastatic spread; only the combination of hRabMab1 and gem/paclitaxel significantly reduced metastatic spread (p=0.0114 vs vehicle, 1-way ANOVA). RNAseq analysis of primary tumor tissue followed by gene set enrichment of differentially expressed genes showed that the addition of hRabMab1 to gem/paclitaxel downregulated tubulin binding and microtubule motor activity. Genes involved in extracellular matrix/collagen production and neovascularization were upregulated in response to gem/paclitaxel; addition of hRabMab1 to gem/paclitaxel tentatively reduced this compensatory effect. In the liver, hRabMab1 reduced liver metastasis as a single agent (p=0.031 vs vehicle) and in combination with gem/paclitaxel (p=0.0054 vs vehicle, 1-way ANOVA). In the surgical incision site, metastatic penetrance was as follows: vehicle, 100%; hRabMab1, 100%; gem/paclitaxel, 44% (4/9); hRabMab1+gem/paclitaxel, 0% (p=0.037715, gem/paclitaxel vs hRabMab1+gem/paclitaxel, Chi square test). Only the combination of hRabMab1 and gem/paclitaxel eliminated leukocytosis; levels of neutrophils, monocytes, eosinophils, and basophils were significantly lower in the hRabMab1+gem/paclitaxel cohort vs gem/paclitaxel cohort (p=0.035, p=0.051, p=0.032, and p=0.026, respectively). Leukocytes recruited from the circulation fuel tumor progression in PDAC. To address the potential significance of white blood cell (WBC) count normalization in our model, we performed correlation analysis between WBC counts and tumor volumes across all cohorts; there was a highly significant positive correlation between these two parameters (R=0.682, p=0.00002). Conclusions. This is the first study demonstrating that hRabMab1 can suppress metastasis in PDAC. hRabMab1’s ability to improve anti-metastatic efficacy of chemotherapy is potentially significant and warrants further investigation. Citation Format: Clayton S. Lewis, Charles Backman, Sabahat Ahsan, Ashley Cliff, Arthi Hariharan, Jen Jen Yeh, Davendra P. S. Sohal, Vladimir Y. Bogdanov. First-in-class humanized antibody targeting alternatively spliced tissue factor augments anti-metastatic efficacy of chemotherapy in a preclinical model of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A085.

Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures

BackgroundOne-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction, skin rashes, musculoskeletal discomfort, and fatigue. This symptom cluster is now referred to as Gulf War Illness (GWI). As the underlying mechanisms of GWI have yet to be fully elucidated, diagnosis and treatment are based on symptomatic presentation. One confounding factor tied to the illness is the high presence of post-traumatic stress disorder (PTSD). Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction. As such, this research endeavor aimed to provide insight into the complex relationship between GWI symptoms, cytokine presence, and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.MethodsSymptom measures were gathered through the Multidimensional fatigue inventory (MFI) and 36-item short form health survey (SF-36) scales and biological measures were obtained through cytokine & cytometry analysis. Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM)-5, into GWI with high probability of PTSD symptoms (GWIH) and GWI with low probability of PTSD symptoms (GWIL). Data was analyzed using Analysis of variance (ANOVA) statistical analysis along with correlation graph analysis. We mapped correlations between immune cells and cytokine signaling measures, hormones and GWI symptom measures to identify patterns in regulation between the GWIH, GWIL, and healthy control groups.ResultsGWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both Healthy control (HC) and the GWIL subgroup. Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity (ANOVA F = 4.7, P = 0.01,) indicating its potential usage as a biomarker for general GWI from control. While the unique identification of GWI with PTSD symptoms was less clear, the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge (ANOVA F > 3.75, P < 0.03). Additional differences in natural killer (NK) cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.ConclusionWe conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.

Immunomodulatory effect of aqueous extract of Termitomyces striatus mushroom on enterohemorrhagic Escherichia coli-infected mice

Enterohemorrhagic Escherichia coli (EHEC) generates Shiga toxins that causes immunosuppression and diarrhea. Synthetic immunomodulatory drugs are associated with numerous severe effects, necessitating the need for substitute therapeutic agents. This study aimed to determine the immunomodulatory activity of aqueous extract of Termitomyces striatus in in mice infected with EHEC. Mice in the positive control, negative control and two extract-treated groups were administered orally with 200µL of 9×108 CFU/mL EHEC. From day 5, the positive control, negative control, and extract-treated mice were orally administered with levamisole (50mg/kg body weight (bw)), phosphate-buffered saline (vehicle), and aqueous extract of Termitomyces striatus (200 and 400mg/kg body weight), respectively. The control mice received the vehicle only. After the experiment, the mice were euthanized, blood was collected, and white blood cells (WBCs) and differentials analyzed using a hematological analyzer. Immunoglobulin G (IgG), interleukin-4 (IL-4) and interferon-gamma (INF-γ) levels were also quantified using enzyme-linked immunosorbent assays. The extract significantly reduced elevated levels of WBCs, neutrophils, monocytes, eosinophils and basophils, as well as significantly enhanced the levels of lymphocytes in EHEC-infected mice (p&lt;0.05). Besides, the extract significantly lowered the levels of INF-γ while significantly increasing the levels of IL-4 and IgG in EHEC-infected mice. Flavonoids, alkaloids, saponins, steroids and phenolics are some of the phytochemicals that were detected in T. striatus. Together, these finding revealed that T. striatus extract modulated immune response in EHEC- challenged mice by lowering leucocyte counts and INF-γ, enhancing lymphocytes, IL-4 and IgG, suggesting that the extract could be developed as an immunomodulatory agent.

Epidemiological and hematological aspects of idiopathic diarrhea in dairy cattle at Sirajganj district of Bangladesh

Cattle diarrhea poses a significant risk to the global livestock sector, leading to considerable economic setbacks and impacting the well-being of animals. This research aimed to assess the clinical and hematological changes associated with idiopathic diarrhea in cattle in the Baghabari area of the Sirajganj District of Bangladesh. The study involved surveying dairy cattle to record their case history, followed by the collection and measurement of hematological indices in those suffering from idiopathic diarrhea. The survey identified 39 diarrheic crossbred cattle (2 males and 37 females), ranging in age from 1 month to 11 years. The findings revealed a higher prevalence of diarrheal cases in cows (94.87%) compared to oxen (5.13%), particularly among pregnant cows (64.86%). The most common historical observations included repeat breeding (81.08%), abortion (78.38%), decreased milk production (43.24%), fever (15.64%), and congenital defects (17.95%) in diarrheic cattle. Hematological analyses indicated a significant increase in lymphocyte and immunoglobulin levels, while eosinophil, basophil, and red blood cell distribution width levels were notably lower in diarrheic cattle compared to healthy ones. However, other hematological parameters remained unaffected. In summary, the study suggests that bovine diarrhea may influence hematological profiles and body physiology, with the extent depending on the disease’s etiology and complexity.

Hematological Profile and Aminotransferase Activity in Kintamani Bali Puppies Injected with High Doses of Ivermectin

Pr Ivermectin toxicity is known to cause harmful side effects or even death in dogs intolerant to the medication. Intolerant dogs have a mutation in the MDR-1 (Multi-Drug Resistance) gene, so they lack the P-glycoprotein gene that removes drugs from the brain. Therefore, this study aimed to determine ivermectin toxicity in Kintamani Bali puppies by examining physiological responses based on hematological profiles and aminotransferase activity after a high-dose injection. A laboratory observational approach was used, and the samples were 25 healthy female Kintamani puppies based on a veterinary examination, aged 3-6 months, weighing 6.32 ± 1.18 kg, randomly divided equally into five treatment groups. The treatments included a placebo (1ml Aqua Pro Injection) as a control, as well as a single dose of ivermectin injection sequentially 200, 400, 800, and 1600 µg/kg subcutaneously. Blood samples were collected before treatment and after 7 and 14 days post-treatment. The hematologic parameters observed included levels of hemoglobin, erythrocytes, hematocrit, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, as well as blood biochemistry, namely aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Observation results after 4 hours of administration of ivermectin at doses of 800 and 1600 µg/kg of puppies showed changes in behavior, restlessness, depression, tremors, mydriasis, hypersalivation, anorexia, and polydipsia. Meanwhile, the results of hematological examination on the seventh day after ivermectin treatment showed a trend of erythropenia, leukocytosis, a decrease in hemoglobin levels, and an increase in aminotransferase enzyme activity. This condition continued until day 14, but the physiological parameter values showed that the puppy’s condition gradually improved compared to the seventh day after treatment. There were significant differences in the blood profile, AST, and ALT of Kintamani puppies injected with ivermectin at doses of 800 and 1,600 ug/kg compared to controls on days 7 and 14 after and before treatment. It was concluded that high-dose ivermectin injections in Kintamani Bali puppies caused toxicity with clinical signs of erythropenia, decreased hemoglobin, leukocytosis, and increased aminotransferase activity.

Investigation into changes in inflammatory and immune cell markers in pre-diabetic patients from Durban, South Africa

The prevalence of pre-diabetes is increasing in rapidly urbanizing cities, especially in individuals aged 25 − 45 years old. Studies also indicate that this condition is associated with aberrant immune responses that are also influenced by environmental factors. This study sought to investigate changes in the concentration of immune cells and select inflammatory markers in patients with pre-diabetes in Durban, South Africa. Blood samples collected from King Edward Hospital, after obtaining ethics approval, were divided into non-diabetic (ND), pre-diabetic (PD) and type 2 diabetic (T2D) using ADA criteria. In each sample, the concentration of immune cells and select inflammatory markers were determined. The results showed a significant increase in eosinophil and basophil levels in the PD group as compared to the ND group. Compared to ND, the PD and T2D groups had significant increases in serum TNFα, CD40L and fibrinogen concentrations. Additionally, there were decreases in serum CRP, IL-6, and P-selectin in the PD group while these markers increased in the T2D group. These findings were indicative of immune activation and highlight the impact of pre-diabetes in this population. More studies are recommended with a higher number of samples that are stratified by gender and represent the gender ratio in the city.

Haematological and Clinical Characterization of Chronic Myeloid Leukemia

A myeloproliferative disorder known as chronic myeloid leukemia (CML) is caused by the clonal proliferation of haematopoietic progenitor stem cell leading to a marked raise in the granulocyte series of cells in the peripheral blood and bone marrow. The present study focused on evaluating clinical and haematological parameters. It is an observational study conducted over a period of 3 years which constitutes 50 diagnosed CML patients. Clinical and haematological details were collected. Prognostic Sokal and European treatment and Outcomes Study (EUTOS) scoring were applied to stratify different risk groups of patients. Study population showed male preponderance. The most common presenting symptom was splenomegaly (98%) followed by anaemia (94%). The patients were divided into Chronic Phase (CP), Accelerated Phase (AP) and Blast phase (BP) in males and females. In males, there was a significant reduction in haemoglobin levels as the disease progressed whereas in females, there was a reduction in haemoglobin levels. Haemoglobin count reflected the anaemic picture and was lowest in the blast phase. The blood cell indices and differential counts were within their normal range in both male and female patients. There was variation in the levels of lymphocytes among males and females but lower than the normal range. Basophil levels were significant between the different phases in females whereas platelet count was significant in males. The current study expected that there would be significant variations between male and female CML patients in a number of haematological measures which can be used as a good prognostic indicator.