Differential White Blood Cell Counts Research Articles

Epstein-Barr in a Patient Presenting with Right Upper Quadrant Pain: A Case Report from the Emergency Department

BackgroundRight upper quadrant abdominal pain and elevated cholestasis blood tests are usually associated with bacterial calculous cholecystitis. However, viral infections, such as Epstein-Barr virus (EBV) can also manifest with a similar clinical picture and is an important differential diagnosis. Case ReportThis case report discusses a young woman presenting to the emergency department with acute right upper quadrant abdominal pain. The initial assessment revealed a positive Murphy's sign, elevated white blood count, and a cholestatic pattern on liver function tests, leading one to suspect bacterial calculous cholecystitis and initiating antibiotic therapy. However, clinical examination also revealed tonsillar exudates and differential white blood cell count revealed monocytosis and lymphocytosis rather than a high neutrophil count. The patient tested positive for EBV. Furthermore, ultrasound and magnetic resonance imaging revealed gallbladder wall edema with no gallstones, leading one to conclude that the clinical manifestation and laboratory results were due to an EBV infection. Antibiotic therapy was ceased and the patient did not require surgical intervention. Why Should an Emergency Physician Be Aware of This?Calculous bacterial cholecystitis usually entails antibiotic therapy and cholecystectomy. It is important to be aware of the differential diagnosis of EBV, as it usually does not require either of these and resolves spontaneously.

The use of tourniquet is useful in terms of blood loss and soft tissue damage in arthroscopic anterior cruciate ligament reconstruction: a retrospective study

Whether a tourniquet should be used for anterior cruciate ligament reconstruction (ACLR) when the operative field is secured remains controversial. Little is known about the influence of not using a tourniquet on total perioperative blood loss and soft tissue damage. The aim of this study was to compare total perioperative blood loss and soft tissue damage with and without tourniquet use during ACLR. Seventy-seven consecutive ACLRs in 76 patients were performed without tourniquet use at our hospital and enrolled in this study (T− group) between November 2018 and September 2021. The control group (T + group) comprised 55 historical ACLRs in 55 patients performed with tourniquet use at our hospital between April 2017 and September 2018. Total perioperative blood loss, calculated from the change in hemoglobin between that preoperatively and on postoperative day (POD) 1, and indicators of soft tissue damage including serum white blood cell (WBC) counts, creatine phosphokinase (CPK), and C-reactive protein (CRP) values measured on POD 1 and POD 7 were compared between groups. Total blood loss was significantly higher in the T− group (339 ± 216 mL) than in the T + group (258 ± 199 mL; P = 0.030). On POD 1, WBC counts were significantly higher in the T− group (9.7 ± 2.4 × 103 cells/µL) than in the T + group (9.1 ± 2.5 × 103 cells/µL; P = 0.043), CPK levels were significantly higher in the T− group (294 ± 417 U/L) than in the T + group (255 ± 88 U/L; P = 0.046), and CRP levels were also significantly higher in the T− group (1.40 ± 1.12 mg/dL) than in the T + group (0.91 ± 0.76 mg/dL; P = 0.016). No significant differences in WBC counts or CPK or CRP levels were seen between groups on POD 7. Total blood loss and soft tissue damage were significantly increased without tourniquet use during ACLR. No advantage was found for not using a tourniquet in terms of blood loss or soft tissue damage.

Mitigation of Benzene-Induced Haematotoxicity in Sprague Dawley Rats through Plant-Extract-Loaded Silica Nanobeads.

Benzene, a potent carcinogen, is known to cause acute myeloid leukaemia. While chemotherapy is commonly used for cancer treatment, its side effects have prompted scientists to explore natural products that can mitigate the haematotoxic effects induced by chemicals. One area of interest is nano-theragnostics, which aims to enhance the therapeutic potential of natural products. This study aimed to enhance the effects of methanolic extracts from Ocimum basilicum, Rosemarinus officinalis, and Thymus vulgaris by loading them onto silica nanobeads (SNBs) for targeted delivery to mitigate the benzene-induced haematotoxic effects. The SNBs, 48 nm in diameter, were prepared using a chemical method and were then loaded with the plant extracts. The plant-extract-loaded SNBs were then coated with carboxymethyl cellulose (CMC). The modified SNBs were characterized using various techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-visible spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The developed plant-extract-loaded and CMC-modified SNBs were administered intravenously to benzene-exposed rats, and haematological and histopathological profiling was conducted. Rats exposed to benzene showed increased liver and spleen weight, which was mitigated by the plant-extract-loaded SNBs. The differential white blood cell (WBC) count was higher in rats with benzene-induced haematotoxicity, but this count decreased significantly in rats treated with plant-extract-loaded SNBs. Additionally, blast cells observed in benzene-exposed rats were not found in rats treated with plant-extract-loaded SNBs. The SNBs facilitated targeted drug delivery of the three selected medicinal herbs at low doses. These results suggest that SNBs have promising potential as targeted drug delivery agents to mitigate haematotoxic effects induced by benzene in rats.

An Observational Study Comparing the Effects of Chloroquine and Artemisinin-Based Combination Therapy on Hematological Recovery in Patients With Plasmodium vivax Malaria.

Introduction Malaria, a common parasitic disease in tropical regions, produces hematological changes in patients. In the present study, we compare hematologic recovery between the chloroquine and artemether-lumefantrine treatment groups of patients with Plasmodium vivax malaria. Methodology This was a cross-sectional observational study comparing hematological parameters, including total and differential white blood cell counts, and platelet counts between two patient groups: one group with 48 patients receiving chloroquine, and the other with 47 patients receiving the artemether-lumefantrine combination. Both groups received primaquine to combat the hypnozoite stage. Results The rate of platelet count recovery was significantly faster in patients treated with the artemether-lumefantrine combination (p-value 0.002). Rates of recovery of the total white blood cell count and neutrophil count were faster with the artemether-lumefantrine combination, while the recovery of the lymphocyte count was faster in patients treated with chloroquine. However, these changes were statistically insignificant (p-values = 0.69, 0.42, and 0.65, respectively). Conclusion Based on hematological recovery, artemisinin combination therapy may be preferred over treatment with chloroquine in cases of P. vivax malaria. However, factors such as the adverse effect profile, cost-effectiveness, and chloroquine resistance need to be considered for the practical applicability of the same.

Investigations of leukocyte and inflammatory markers in pregnancies complicated by preeclampsia

ObjectivesPreeclampsia is a frequent and potentially fatal pregnancy complication. It can be challenging to make a timely diagnosis. Identifying clinically useful biochemical markers would be a remedying tool to support the diagnosis of preeclampsia. The aim was to investigate differential cell counts and acute phase reactants as diagnostic markers of preeclamptic third-trimester pregnancies and in relation to pregnancy term, gravidity and the severity of hypertension. MethodsBased on a cohort of 421 pregnant women, we included 174 participants (case n = 84, control n = 90) during the third trimester. Peripheral blood was sampled to measure differential white blood cell counts and acute phase reactants on the day of inclusion. ResultsThe neutrophil-to-lymphocyte ratio and plasma haptoglobin levels were significantly increased in healthy pregnancies compared with preeclamptic pregnancies. Plasma ferritin levels and albumin levels were respectively increased and decreased in cases of preeclampsia compared with controls. Albumin was specific among multigravida. Plasma transferrin and high-sensitivity C-reactive protein (hs-CRP) levels were significantly decreased and increased, respectively, in cases with preterm preeclampsia compared with term preeclampsia. ConclusionPlasma ferritin and albumin levels reflected higher inflammation in cases with preeclampsia compared with healthy pregnancies; the same did plasma transferrin and hs-CRP levels in preterm versus term preeclampsia. When considering the normal ranges plasma albumin and hs-CRP levels identified preeclamptic from healthy third-trimester pregnancies and preterm from term preeclampsia cases, respectively, with near-acceptable diagnostic performances. Further validation of the diagnostic value will require larger sample-sized studies with paired plasma and serum samples.

Shift Work is Associated with an Elevated White Blood Cell Count: A Systematic Review and Meta-Analysis.

The white blood cell (WBC) count increases significantly in reaction to infections and certain chronic diseases. Shift employment increases the risk for chronic low-grade inflammation and the progression of several chronic diseases. The objective of this study was to systematically evaluate the evidence from studies on total and differential WBC counts in shift employees. A literature search was performed in PubMed®, Web of Science, and Scopus databases using keywords for research published before March 1, 2022. A meta-analysis was conducted for total and differential WBC counts using a random-effects approach. A total of 25 studies covering a sample of 37,708 day and shift employees were included in this review. The studies represented America, Europe, East Asia, and Middle East. A significant increase in the total counts (×109/L) of WBC [mean difference (MD) = 0.43; 95% confidence interval (CI): 0.34-0.52; P < 0.001], lymphocytes (MD = 0.16; 95% CI: 0.02-0.30; P = 0.02), monocytes (MD = 0.04; 95% CI: 0-0.07; P = 0.03), and eosinophils (MD = 0.01; 95% CI: 0-0.01; P = 0.03) was observed in shift workers compared to the day counterparts. However, neutrophils and basophils were not significantly different between the groups. Shift work significantly increases the total and differential blood counts in peripheral circulation. Therefore, total and differential WBC counts represent a relatively inexpensive biomarker for diagnostics and prognostics of diseases in shift workers.

Thermostability and Immunostimulatory Activity of Cationic Liposome-based Newcastle Disease Virus Vaccine

Cold storage is a huge challenge in maintaining vaccine potency especially in low and middle income countries (LMIC). The aim of this research was to investigate the heat and freeze-thaw stability of Newcastle disease virus (NDV) vaccine encapsulated in 1,2-dioleoyl-3-trimethyl ammonium propane (DOTAP) cationic liposomes as well as its immunostimulatory activity. DOTAP cationic liposomes were prepared using the thin-film hydration technique and characterized for morphology, particle size, polydispersity index, zeta potential and encapsulation efficiency. Experimental birds were challenged with Herts 33 velogenic strain of NDV. Haemagglutination inhibition test was used to assess the formation of antibodies in the birds. The cationic liposomes were further stored at 28 oC or subjected to freeze-thaw cycles for 7 weeks and then assessed for stability using the same parameters of particle size, polydispersity index, zeta potential, morphology, antibody titre or differential white blood cell count. Using TEM, the morphology of the liposomes was found to be spherical, and using Malvern Zetasizer, particle size was in the nanosize range. Zetapotential and polydispersity indices were positive and below 0.1. The HI test showed that the DOTAP cationic liposomes stimulated a higher titre of antibodies than the commercial vaccine. Heat and freeze-thaw stability studies after 7 weeks of storage showed slight aggregation and elevated particle sizes and wider distribution. The HI titer was appreciably lower after secondary immunization with the DOTAP cationic liposomes stored at 28 oC but elevated for the product kept at freeze-thaw conditions. The immunized birds were 100 % protected from the virulent strain of NDV. In conclusion, the development of the DOTAP-cationic liposomes encapsulating NDV vaccine administered orally was found to be more stable under freeze-thaw conditions than when it was exposed to heat for 7 weeks. The liposome-based vaccine had more immunostimulatory effects than the commercial sample.

Systemic inflammation response index and aggregate inflammation systemic index in male and female cancers: Implication for gender based immunotherapy

&lt;b&gt;Background:&lt;/b&gt; Several blood cell ratios have emerged as easy and minimally evasive inflammatory markers of cancer progression and management. Systemic inflammation response index (SIRI) and aggregate inflammation systemic index (AISI), which are reliable indicators of inflammation because they are calculated using more than two immune cells, have not been widely studied. The present study is particularly important in delineating gender-based cancers and to suggest inflammation based therapy.&lt;br /&gt; &lt;b&gt;Methods: &lt;/b&gt;SIRI and AISI were calculated from differential white blood cell counts using automatic hematology analyzer in 50 cervical patients, 50 prostate cancer patients and 61 corresponding controls.&lt;br /&gt; &lt;b&gt;Results&lt;/b&gt;: Mean values of SIRI and AISI were significantly raised in cervical cancer patients and prostate cancer patients compared with corresponding control. The mean white blood cell and neutrophil counts were significantly raised while SIRI, monocyte counts and AISI were significantly reduced in prostate cancer patients compared with cervical cancer patients.&lt;br /&gt; &lt;b&gt;Conclusions&lt;/b&gt;: This study suggests that inflammation is a phenomenon in cervical- and prostate- cancer patients but the impact of inflammation might be more in cervical cancer patients, suggesting that sex hormones might limit the efficacy of broad spectrum single cancer immunotherapy for both sexes.

Anti-Inflammatory and Antinociceptive Activity of Herbal Lipospheres of Pentaclethra macrophylla (Fabaceae) Stem Bark Extract

Purpose: Inflammation of various degrees is common among humans. There are associated side effects with orthodox delivery systems and anti-inflammatory agents; hence, the study investigated the characteristics of herbal lipospheres and the anti-inflammatory potency of the lipospheres formulated from Pentaclethra macrophylla with the view to having a drug with a better delivery system and lesser side effects. Methods: Herbal lipospheres were formulated using solidified reverse micellar solutions (SRMS) of P90H and goat fat and characterized for particle size and morphology, pH time dependent analysis, encapsulation efficiency (EE%), and Fourier Transform infrared spectroscopy. The in vitro antinociceptive and anti-inflammatory studies were carried out using membrane stabilization by hypotonicity-induced hemolysis and the determination of anti-platelet aggregatory activity models. The in vivo antinociceptive and anti-inflammatory studies on egg albumin- and formaldehyde-induced arthritis models were conducted. A total white blood cell count and differential blood count were carried out on the rats. Results: The results showed that there was no change in pH for the PM-unloaded lipospheres and 2.5 g of PM-loaded lipospheres from day 1 to day 7, but there was a mild variation in the rest of the formulations. The EE ranged from 35.2% to 94%, increasing according to the drug concentration. The photomicrographs of the lipospheres showed that the particles were spherical in shape. The particle sizes were within the acceptable range for lipospheres. FTIR showed no interaction. In the arthritis study, PM-loaded lipospheres inhibited edema consistently throughout the duration of observation. Inhibition of the membrane increased steadily with an increase in concentration of PM in the lipospheres and the standard drug. The platelet aggregatory inhibition decreased steadily with an increase in concentration of the PM in the lipospheres as well as the standard. The T50 dose of PM had the highest percentage of WBC, and it decreased as the treatment doses increased from T100 to T200. There were no significant differences among the Neutrophil counts of the different groups. Conclusions: The study, therefore, showed that the methanol extract of Pentaclethra macrophylla formed efficient herbal lipospheres with antinociceptive and anti-inflammatory activities.

Clinical Significance of Immature Neutrophils in Relation to Disease Activity in Psoriatic Arthritis Patients

Abstract Background Psoriatic arthritis (PsA) is a complex type of progressive inflammatory arthritis associated with psoriasis. Prevalence of PsA has been reported 5.8–40.9% among patients suffering from psoriasis. A recent meta-analysis indicated that there is no gender predilection in patients with PsA. It shares genetic and clinical features with other forms of spondyloarthritis and affects different structures of the musculoskeletal system in addition to the skin and the nail. Neutrophils are crucial responders of the innate immune response, but the role played by neutrophils in psoriasis has not been well characterized. This thesis discussed the current understanding of the role and potential mechanisms of immature neutrophils in psoriatic arthritis. Objective To study the relation between immature neutrophils in blood and disease activity in psoriatic arthritis patients. Methods This randomized control trial, done on 50 PsA patients from Physical medicine, Rheumatology and Rehabilitation and Dermatology outpatient clinics of Ain Shams University hospital, included by CASPAR criteria, subjected to full medical history taking and thorough clinical examination with calculation of SPARCC, ASDAS and PASI scores.laboratory evaluation include CBC with differential white blood cell count for Immature Neutrophils percentage, ESR, CRP and Rheumatoid factor.CBC was compared with 20 age and sex matched healthy controls. Results The Immature Neutrophils mean ± SD(%) was found to be 5.99±1.57 in patients and was statistically significantly higher in them than in controls 2.25±1.16(P &amp;lt; 0.037) and it was statistically significantly correlated with disease activity according to ASDAS score, SPARCC, PASI score, ESR, CRP, RBCS, WBCS, Platelets, Enthesitis, Dactylitis, skin and nail affection. Conclusion This study highlighted the role of immature neutrophils as a novel biomarker for disease activity in psoriatic arthritis.

The relationship between heated cigarette smoking and blood white blood cell count: a population-based cross-sectional study

ObjectivesConventional cigarette smoking increases inflammation and white blood cell (WBC) counts. However, there have been limited studies on the relationship between heated cigarette smoking and WBC counts. This study aimed to examine this relationship using nationally representative population-based health data. Study designThis was a population-based cross-sectional study. MethodsThe Korea National Health and Nutrition Examination Survey database was used to analyze this relationship. Data related to sex, age, body mass index (BMI), WBC count, and smoking history were obtained from the database. The smoking-related questionnaires included smoking status, smoking type (heated or conventional cigarettes), and smoking amount. The summary statistics of the WBC counts were calculated according to sex, smoking status, and smoking type. In addition, the exposure–response relationship between the smoking amount and WBC count was examined by smoking type, controlling for sex, age, and BMI. ResultsIn total, 9747 WBC measurements were used in the analyses. WBC count increased in conventional cigarette smokers, while there was no significant difference in WBC count between heated cigarette smokers and non-smokers. The WBC count showed a positive dose–response relationship with the smoking amount in both conventional and heated cigarette smokers. ConclusionsThe results confirm that conventional cigarette smoking increases WBC counts. Furthermore, the results suggest that heated cigarette smoking does not lead to a significant increase in WBC counts, although it indicates a potential dose–response relationship with WBC count. Further research with larger sample sizes is needed to confirm whether these results reflect true associations.

COVID-19 Disease in Pediatric Solid Organ Transplantation from Alpha to Omicron: A High Monocyte Count in the Preceding Three Months Portends a Risk for Severe Disease.

Planning for future resurgences in SARS-CoV-2 infection is necessary for providers who care for immunocompromised patients. to determine factors associated with COVID-19 disease severity in immunosuppressed children. a case series of children with solid organ transplants diagnosed with SARS-CoV-2 infection between 15 March 2020 and 31 March 2023. a single pediatric transplant center. all children with a composite transplant (liver, pancreas, intestine), isolated intestine transplant (IT), isolated liver transplant LT), or simultaneous liver kidney transplant (SLK) with a positive PCR for SARS-CoV-2. SARS-CoV-2 infection. We hypothesized that children on the most immunosuppression, defined by the number of immunosuppressive medications and usage of steroids, would have the most severe disease course and that differential white blood cell count in the months preceding infection would be associated with likelihood of having severe disease. The hypothesis being tested was formulated during data collection. The primary study outcome measurement was disease severity defined using WHO criteria. 77 children (50 LT, 24 intestine, 3 SLK) were infected with SARS-CoV-2, 57.4 months from transplant (IQR 19.7-87.2). 17% were ≤1 year post transplant at infection. 55% were male, 58% were symptomatic and ~29% had severe disease. A high absolute lymphocyte count at diagnosis decreased the odds of having severe COVID-19 disease (OR 0.29; CI 0.11-0.60; p = 0.004). Conversely, patients with a high absolute monocyte count in the three months preceding infection had increased odds of having severe disease (OR 30.49; CI 1.68-1027.77; p = 0.033). Steroid use, higher tacrolimus level, and number of immunosuppressive medications at infection did not increase the odds of having severe disease. The significance of a high monocyte count as predictor of severe disease potentially confirms the importance of monocytic inflammasome-driven inflammation in COVID-19 pathogenesis. Our data do not support reducing immunosuppression in the setting of infection. Our observations may have important ramifications in resource management as vaccine- and infection-induced immunity wanes.

Feasibility of manufacture of chimeric antigen receptor-regulatory T cells from patients with end-stage renal disease

BackgroundGene-modified cell therapy with regulatory T cells (Tregs) is a promising approach to prevent graft rejection and induce immunological tolerance in organ transplantation. We are developing a cell therapy comprising autologous naïve Tregs that are isolated from leukapheresate, transduced with lentiviral vector encoding a chimeric antigen receptor (CAR) recognising human leukocyte antigen class I molecule A*02 (HLA-A*02), and expanded ex vivo before cryopreservation as resultant drug product (TX200-TR101). In an ongoing first-in-human study (NCT04817774), kidney transplant recipients will receive a single infusion of TX200-TR101 2–3 months after transplantation. The phase 0 study described here evaluated the feasibility of manufacture of TX200-TR101 for the target population, i.e., end-stage renal disease (ESRD) necessitating kidney transplantation. Participants in this study did not receive an infusion of drug product.MethodsFour patients with ESRD and HLA-A*02 negative typing underwent leukapheresis to collect starting material for manufacture of TX200-TR101. Manufacturing success criteria were predefined as a batch of CAR-Tregs with cell quantity in each batch ≥ 104 cells/kg body weight, cell viability ≥ 70%, transduction efficiency ≥ 20% and hypomethylation of the FoxP3 gene (Treg-specific demethylated region [TSDR]) ≥ 80%. Other manufacturing variables included Treg identity and maturation by phenotyping, residual bead count, vector copy number, endotoxin level, sterility, and presence of mycoplasma. The characteristics of leukapheresate starting material and drug product from patients with ESRD were compared with those from commercially purchased leukapheresate from 10 healthy donors.ResultsNo safety issues were identified during leukapheresis collections. Batches of drug product were manufactured from all 4 patients with ESRD and met the predefined success criteria. There was some variability in leukapheresate starting material in terms of volume of apheresis and total leukocyte counts between patients with ESRD and healthy donors, but percentage differential white blood cell counts were comparable. The quality, quantity and functional activity of manufactured CAR-Tregs were similar between ESRD patients and healthy donors. CAR-Treg drug product from one patient with pre-existing lymphopenia had similar high quality but reduced cell quantity compared with batches from the other patients with ESRD, although yield was still above the predefined target minimum number of cells.ConclusionsManufacture of high-quality naïve CAR-Tregs from patients with ESRD is safe and feasible.

Sex Differences in Immune Cell Infiltration and Hematuria in SCI-Induced Hemorrhagic Cystitis.

Rats manifest a condition called hemorrhagic cystitis after spinal cord injury (SCI). The mechanism of this condition is unknown, but it is more severe in male rats than in female rats. We assessed the role of sex regarding hemorrhagic cystitis and pathological chronic changes in the bladder. We analyzed the urine of male and female Sprague-Dawley and Fischer 344 rats after experimental spinal cord contusion, including unstained microscopic inspections of the urine, differential white blood cell counts colored by the Wright stain, and total leukocyte counts using fluorescent nuclear stains. We examined bladder histological changes in acute and chronic phases of SCI, using principal component analysis (PCA) and clustered heatmaps of Pearson correlation coefficients to interpret how measured variables correlated with each other. Male rats showed a distinct pattern of macroscopic hematuria after spinal cord injury. They had higher numbers of red blood cells with significantly more leukocytes and neutrophils than female rats, particularly hypersegmented neutrophils. The histological examination of the bladders revealed a distinct line of apoptotic umbrella cells and disrupted bladder vessels early after SCI and progressive pathological changes in multiple bladder layers in the chronic phase. Multivariate analyses indicated immune cell infiltration in the bladder, especially hypersegmented neutrophils, that correlated with red blood cell counts in male rats. Our study highlights a hitherto unreported sex difference of hematuria and pathological changes in males and females' bladders after SCI, suggesting an important role of immune cell infiltration, especially neutrophils, in SCI-induced hemorrhagic cystitis.

Inhibitory effect of hydroalcoholic extract of Cunila spicata Benth. on phlogistic agents-induced cellular migration in the airways of mice.

Cunila spicata Benth. Is a creeping and aromatic plant that has an ethnopharmacological indication in the southern region of Brazil, in the Araucaria Forest biome. It's used as an alternative therapy for respiratory diseases for men and animals since the "tropeirista" movement in colonial Brazil. Investigate the influence of oral administration of hydroalcoholic extract of C. spicata (HECS) on cellular inflammatory processes in the airways of mice. The HECS was obtained by the ultrasound-assisted technique. Phytochemical analysis of the volatile compounds was performed using gas-chromatography with mass spectrometry. To investigate the biological activity of HECS, the animals were pre-treated with HECS orally 1h before and the bronchoalveolar lavage (BAL) model was used, in which the animals were subjected to inhalation of different pro-inflammatory agents such as carrageenan (CAR), histamine (HIST), capsaicin (CAP), bradykinin (BK), and 48/80 compound (C48/80). After sacrifice, BAL sample was collected from the bronchi and was analyzed for total and differential white blood cell counts, compared with control groups. Fourteen volatile phytocompounds were identified in the HECS, the main ones being 2-bornanone, menthofuran and camphene. Among the HECS treated animals, all showed significant maximal inhibition (MI) when challenged with pro-inflammatory agents by nebulization. In the group of animals that received CAR, the MI was 72.77±3.88%, compared to the negative control (NC). There was a predominance of lymphocytes (59.18±4.07%). For the HIST group, MI was 64.03±4.33%, in relation to the NC, with predominance in macrophages number (76.53±2.78%). In the CAP group, the MI obtained was 38.90±11.31%, with greater macrophage migration occurring (80.98±3.44%) in the higher dose. For animals subjected to BK inhalation, the MI was 48.63±3.95% with macrophages predominance (64.33±10.04%). In the group that received C48/80 inhalation, the MI was 40.25±5.30% (100mgkg-1), with higher occurrence of macrophages (72.97±4.23%). Our results suggest that HECS had a non-specific inhibitory effect on cellular migration induced by different pro-inflammatory agents, reducing inflammation in airways of mice. These effects coincide and support its ethnopharmacological use as an alternative medicine for respiratory diseases in regions where the plant is prevalent.

Association Between Neutrophil-Lymphocyte Ratio and 30-Day Infection and Thrombotic Outcomes After Intraventricular Hemorrhage: A CLEAR III Analysis.

Serum neutrophil-lymphocyte ratio (NLR) is a surrogate marker for the inflammatory response after intracerebral hemorrhage (ICH) and is associated with perihematomal edema and long-term functional outcomes. Whether NLR is associated with short-term ICH complications is poorly understood. We hypothesized that NLR is associated with 30-day infection and thrombotic events after ICH. We performed a post hoc exploratory analysis of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial. The study exposure was the serum NLR obtained at baseline and on days 3 and 5. The coprimary outcomes, ascertained at 30days, were any infection and a thrombotic event, defined as composite of cerebral infarction, myocardial infarction, or venous thromboembolism; both infection and thrombotic event were determined through adjudicated adverse event reporting. Binary logistic regression was used to study the relationship between NLR and outcomes, after adjustment for demographics, ICH severity and location, and treatment randomization. Among the 500 patients enrolled in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial, we included 303 (60.6%) without missing data on differential white blood cell counts at baseline. There were no differences in demographics, comorbidities, or ICH severity between patients with and without data on NLR. In adjusted logistic regression models, NLR ascertained at baseline (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01-1.07, p = 0.03) and NLR ascertained at day 3 were associated with infection (OR 1.15; 95% CI 1.05-1.20, p = 0.001) but not with thrombotic events. Conversely, NLR at day 5 was associated with thrombotic events (OR 1.07, 95% CI 1.01-1.13, p = 0.03) but not with infection (OR 1.13; 95% CI 0.76-1.70, p = 0.56). NLR at baseline was not associated with either outcome. Serum NLR ascertained at baseline and on day 3 after randomization was associated with 30-day infection, whereas NLR obtained on day 5 was associated with thrombotic events after ICH, suggesting that NLR could be a potential early biomarker for ICH-related complications.

Assessment of subchronic toxicity and toxicokinetics of AG NPP709 in Sprague-Dawley rats

Ethnopharmacological relevanceHedera helix L. (HH) leaves and Coptidis rhizoma (CR) have traditionally been used to treat respiratory conditions. AG NPP709, which is formulated using extracts of both these herbs, has been developed as an expectorant and antitussive. Aim of the studyThe objective was to evaluate the subchronic toxicity and toxicokinetic characteristics of AG NPP709 in laboratory rats. Materials and methodsAG NPP709 was orally administered to rats at doses of up to 2.0 g/kg/day for a duration of 13 weeks. Various health parameters were measured throughout the treatment period. At the end of the treatment, a necropsy was conducted and additional parameters were analyzed. Toxicokinetic analyses were also performed on hederacoside C and berberine, the active components of HH leaves and CR, respectively, in the plasma of rats treated with AG NPP709. ResultsAG NPP709-treated rats exhibited several health issues, such as reduced feed intake, altered differential white blood cell (WBC) count, increased plasma Alb/Glo ratio in females, and reduced kidney weight in males. However, these changes appeared to be incidental and fell within the typical range for healthy animals of this species. Additionally, toxicokinetic analysis of hederacoside C and berberine showed no accumulation in the plasma of rats during the repeated treatments with AG NPP709. ConclusionsOur study demonstrates that AG NPP709 does not have any harmful effects on rats under experimental conditions. Based upon these findings, the no observed adverse effect level of AG NPP709 can be estimated to be 2.0 g/kg/day in rats.

Effects of Hydrogen Gas Inhalation on Community-Dwelling Adults of Various Ages: A Single-Arm, Open-Label, Prospective Clinical Trial.

Molecular hydrogen (H2) is a versatile therapeutic agent. H2 gas inhalation is reportedly safe and has a positive impact on a range of illnesses, including Alzheimer's disease (AD). Herein, we investigated the effects of 4 weeks of H2 gas inhalation on community-dwelling adults of various ages. Fifty-four participants, including those who dropped out (5%), were screened and enrolled. The selected participants were treated as a single group without randomization. We evaluated the association between total and differential white blood cell (WBC) counts and AD risk at individual levels after 4 weeks of H2 gas inhalation treatment. The total and differential WBC counts were not adversely affected after H2 gas inhalation, indicating that it was safe and well tolerated. Investigation of oxidative stress markers such as reactive oxygen species and nitric oxide showed that their levels decreased post-treatment. Furthermore, evaluation of dementia-related biomarkers, such as beta-site APP cleaving enzyme 1 (BACE-1), amyloid beta (Aβ), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor A (VEGF-A), T-tau, monocyte chemotactic protein-1 (MCP-1), and inflammatory cytokines (interleukin-6), showed that their cognitive condition significantly improved after treatment, in most cases. Collectively, our results indicate that H2 gas inhalation may be a good candidate for improving AD with cognitive dysfunction in community-dwelling adults of different ages.

Haematological and Biochemical Changes in Albino Rats in Response to Bisphenol A (BPA) Exposure

The aim of this study was to investigate the haematological and biochemical alterations in albino rats induced by bisphenol A (BPA). Fifteen adult male albino rats were procured and separated into 3 different groups viz: group 1 (control), group 2 (50 mg/kg), group 3 (250 mg/kg); and were orally administered BPA at doses of 50 and 250 mg/kg/week. After 6 weeks of exposure, blood samples were collected for haematological and biochemical assay. The parameters analyzed included: red blood cell count, haemoglobin concentration, packed cell volume, white blood cell count, differential white blood cell count, kidney and liver function tests. The results obtained revealed that there was a sequence of significant decrease (P&lt;0.05) from the control group to group 3 (250 mg//kg) of the BPA-treated groups in the following parameters; total RBC count 7.33-4.40, Hb concentration 16.63-11.13 and PCV count 43.67-34.67. A significant increase (P&lt;0.05) was observed in all leucogram values of BPA-treated groups when compared to the control. The serum levels of AST (44.67-71.00), ALT (13.33-46.67), ALP (64.00-86.67), Na+, K+, urea and creatinine significantly increased (P&lt;0.05) in the groups that received BPA-treatment. There was also a non-significant reduction (P&gt;0.05) in total protein (72.67-61.00) and albumin (49.00-25.00) in BPA-treated groups when compared to the control. These findings demonstrate that exposure of albino rats to BPA resulted in haematological defects and alteration in several biochemical parameters that indicate renal and hepatic toxicity.

Effect of Allium cepa extract on total and differential WBC, TP level, oxidant and antioxidant biomarkers, and lung pathology in ovalbumin-sensitized rats.

Previous studies have shown that Allium cepa (A. cepa) has relaxant and anti-inflammatory effects. In this research, A. cepa extract was examined for its prophylactic effect on lung inflammation and oxidative stress in sensitized rats. Total and differential white blood cell (WBC) count in the blood, serum levels of oxidant and antioxidant biomarkers, total protein (TP) in bronchoalveolar lavage fluid (BALF), and lung pathology were investigated in control group (C), sensitized group (S), and sensitized groups treated with A. cepa and dexamethasone. Total and most differential WBC count, TP, NO2, NO3, MDA (malondialdehyde), and lung pathological scores were increased while lymphocytes, superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in sensitized animals compared to controls (p < 0.01 to p < 0.001). Treatment with all concentrations of extract significantly improved total WBC, TP, NO2, NO3, interstitial fibrosis, and emphysema compared to the S group (p < 0.05 to p < 0.001). Two higher concentrations of the extract significantly decreased neutrophil and monocyte count, malondialdehyde, bleeding and epithelial damage but increased lymphocyte, CAT, and thiol compared to the S group (p < 0.05 to p < 0.001). Dexamethasone treatment also substantially improved most measured parameters (p < 0.05 to p < 0.001), but it did not change eosinophil percentage. It was proposed that A. cepa extract could affect lung inflammation and oxidative stress in sensitized rats.