Mean Serum Concentrations Research Articles

Population pharmacokinetic modeling study and discovery of covariates for the antidepressant sertraline, a serotonin selective reuptake inhibitor

The purpose of this study was to discover effective covariates related to explanation of inter-individual pharmacokinetic (PK) variations through population pharmacokinetic (Pop-PK) modeling for sertraline and to provide insight into establishing scientific regimen. The bioequivalence results of sertraline performed on 24 healthy Korean men and the physiological and biochemical parameters derived from each individual were used as data to develop a Pop-PK model of sertraline for Koreans. And the relevant effectiveness of ∗10 allele polymorphisms of CYP2D6 in sertraline PK polymorphisms was further confirmed through a modeling approach. The Pop-PK profiles of sertraline were explained by the basic structure of sequential 2-absorption with 1-compartment, and in terms of inter-individual PK diversity, the volume of distribution could be significantly correlated with estimated glomerular filtration rate (eGFR) and clearance with total protein levels. CYP2D6∗10 allele was not significant in interpreting sertraline PK diversity. As a result of model simulation, the concentration of sertraline in serum significantly increased as total protein and eGFR levels became higher and lower, respectively. The mean serum concentrations of sertraline at steady-state differed by up to 2.12 times from 10.36 to 22.02 ng/mL depending on changes in total protein and eGFR levels, and the fluctuations between the maximum and minimum concentration values ranged from 2.02 to 29.51 to 4.31–63.78 ng/mL. The factor that significantly influenced change in mean serum concentration of sertraline at steady-state was the total protein level, which was interpreted to be closely related to the change in clearance due to the high serum protein binding of sertraline.

Comparative Bioequivalence Studies of doxysam and doxycycline (Pfizer) by reversed phase HPLC.

Isocratic high performance liquid chromatography on reversed phase a (150x 4.6 mm I.D), 5 ?m ?-Bondapak RP-8 column (with acidic mobile phase allow the separation of doxcycycline hydrochloride with low detection limit of 0.2 µg/ml detected by UV set at 226 nm. The method was validated for Doxycycline between 0.156- to 5 µg/ml. The concentration of doxycycline was assessed in two single dose randomized crossover studies with intervals of one week between two period. In sera of 20 adults healthy male volunteers with average age of (42 + 10) year, body weight 48-85 kg, body height of (160-185cm) after a single dose of doxycycline hydrochoride 100 mg in form of capsules were orally administrated for both formulations. The blood samples (2ml) were drawn concomitantly from 0.5 – 24 hours. µg The pharmacokinetics parameter were obtained from the mean serum concentration measured at various sampling times for both formulations. The maximum peak concentration (Cmax) of doxycycline reference drug from Pfizer In serum was (3.1 +0.094 µg /ml) attained in 2 hrs. While the maximum concentration (Cmax) of test drug doxysam (2.8 +0.098 µg /ml) attained in about 2 hrs, both drug have long elimination time with half time of approximately (13 hrs.) Both test and reference drug were show no significant difference in pharmacokinetics parameters, so they were considered to be bioequivalent.

The Role of Omentin-1 and Fibroblast Growth Factor-23 in Iraqi Patients with Prostate Cancer during Chemotherapy

Background: Omentin-1 is mainly expressed in stromal vascular cells of adipose tissue and can also be expressed in airway goblet cells, mesothelial cells, and vascular cells. Fibroblast growth factor 23 (FGF-23), generated by bone cells, regulates phosphate and vitamin D metabolism by regulating phosphate reabsorption in the kidneys and inhibiting vitamin D activation. Vitamin D is a fat-soluble vitamin that regulates calcium absorption, bone health, and immunological function. Prostate cancer is a significant health concern for men worldwide. Several studies demonstrated a link between these variables and cancer as they exert important anti-inflammatory, antioxidative, and anti-cancer functions. Objectives: To assess the impact of Omentin and FGF-23 biochemical functions, as well as the anti-cancer properties of vitamin D. Subjects and methods: This is a case-control study on serum samples collected from Iraqi prostate cancer patients after receiving chemotherapy at Al Amal Center in Imam Hussein Medical City in Karbala between November 2022 to May 2023. The serum samples were collected from two groups: control group consisted of 30 healthy males. Patient group consisted of 30 prostate cancer patients after receiving chemotherapy, both groups aged 45 – 80 years. The two groups were matched for body mass index. ELISA technology was used to estimate serum levels of the aforementioned biochemical parameters with vitamin D. Results: patient group had a significantly higher FGF-23 level than control group (309.5±41.65) versus (163.1±22.4) (p<0.001). On the other hand, Irisin, Omentin and Vitamin D mean serum concentrations were significantly lower in-patient group (15.2±4.24), (13.8±4.28) and (4.4±0.69) (p<0.001), respectively, compared to control group (60.8±3.5), (38.8±6.59), and (18.9±2.36), respectively. (ROC) curve analysis identified the best AUC values of FGF-23, Omentin, and Vitamin D (0.995, 0.959, 0.937), respectively, which suggests a high level of accuracy. Conclusions: These parameters may serve as critical indicators for prostate cancer patients and their disease progress. Vitamin D insufficiency is a risk factor for these individuals.

Serum Interleukin (IL)-6, Lipid Profile, and Association With Disease Severity in Patients With Psoriasis: A Cross-Sectional Study.

This study estimated the lipid profile and inflammatory biomarker (interleukin-6, IL-6) levels in patients with psoriasis and explored the association between lipid profiles and inflammatory biomarkers (IL-6) in assessing the severity of the disease. This cross-sectional study was conducted in the Department of Biochemistry, in association with the Department of Dermatology, at the Veer Surendra Sai Institute of Medical Sciences and Research, Burla, from November 2022 to June 2023. A fully automated analyzer (Cobas C311, Roche Diagnostics, Mannheim, Germany) was used to estimate the lipid profile, while the enzyme-linked immunosorbent assay (Erba, Transasia Bio-medicals Ltd., Mumbai, India) was used to estimate the inflammatory marker (IL-6). Data were analyzed using Statistical Package for the Social Sciences version 21.0 (IBM Corp., Armonk, NY). An unpaired t-test was conducted to examine the relationship between two variables. A p value of <0.05 was considered significant. The correlation among IL-6, lipid profile, and psoriasis area severity index (PASI) score was analyzed using Pearson's correlation coefficient. Quantitative data were expressed as means and standard deviations. Of the 102 study participants, 68 had psoriasis alone, and 34 had psoriasis with arthritis (psoriatic arthritis, PsA). Higher mean serum concentrations of IL-6, total cholesterol (TC), low-density lipoprotein, and triglycerides were found in patients with PsAcompared to those with psoriasis alone. In patients with PsA, TCand IL-6showed a strong positive correlation with the PASIscore. In contrast, high-density lipoprotein showed a negative correlation with PASI (r = -0.036, p < 0.05). In conclusion, our study revealed lipid profile abnormalities and increased IL-6activity in PsA patients. By measuring inflammatory markers (IL-6) and lipid profiles early in the disease process, we can employ preventive strategies to better manage and improve survival and quality of life in patients with psoriasis.

Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with gout and hyperuricemia

BackgroundWe aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA).MethodsThe study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 and 2001–2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models.ResultsAmong participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses.ConclusionsSerum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.

Vitamin D and Muscle Status in Inflammatory and Autoimmune Rheumatic Diseases: An Update.

Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: "vitamin D, muscle, rheumatic diseases." Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020-2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold.

The Role of Pro-Inflammatory Chemokines CCL-1, 2, 4, and 5 in the Etiopathogenesis of Type 2 Diabetes Mellitus in Subjects from the Asir Region of Saudi Arabia: Correlation with Different Degrees of Obesity.

Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles. We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia. In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures. T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects. Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Stapokibart in Healthy Volunteers and Adult Subjects with Atopic Dermatitis.

Stapokibart, a novel humanized anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits the signaling of IL-4 and IL-13, which are key drivers of type2 inflammation in atopic dermatitis (AD). This study aimedto assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of stapokibart in a randomized, double-blind, placebo-controlled single ascending dose (SAD) study and a multiple ascending dose (MAD) study. The SAD study enrolled 33healthy male adults aged 18-65years at a single center. The MAD study enrolled 39 patients with moderate-to-severe AD aged 18-70years at seven centers. Enrolled subjects were randomized to subcutaneous (SC) doses of stapokibart (75-600mg) or placebo. Serum thymus and activation-regulated chemokine (TARC) and total immunoglobulinE (IgE) were measured as PD biomarkers for stapokibart. Similar PK characteristics were observed in healthy volunteers and subjects with AD after the initial administration. Stapokibart exhibited non-linear pharmacokinetics in both types of subjects. Following single doses, the mean maximum serum concentration (Cmax) ranged from 5.3 to 63.0μg/mL, median Tmax ranged from 3.0 to 7.0days, mean terminal half-life (t1/2z) ranged from 2.39 to 7.43days, and mean apparent volume (Vz/F) ranged from 3.64 to 6.73L in healthy subjects. The mean AUC accumulation ratio was 2.29 in subjects with AD after three doses of stapokibart 300mg administered every 2weeks. The median serum total IgE and TARC levels on day43 decreased from baseline by 14.9-25.2% and 48.6-77.0%, respectively, among subjects with AD receiving three doses of stapokibart. No subjects developed grade ≥ 3 adverse events (AEs) or serious AEs or discontinued the study because of AEs. The incidence of AEs was similar between stapokibart and placebo groups. Stapokibart showed favorable pharmacokinetics, pharmacodynamics, safety, and tolerability in the SAD and MAD studies. Based on these results, phaseII and phaseIII trials of stapokibart have been performed in subjects with moderate-to-severe AD. ClinicalTrials.gov Identifier NCT06161090 (29 November, 2023), NCT04893941 (15 May, 2021).

Topical Solution for Retinal Delivery: Bevacizumab and Ranibizumab Eye Drops in Anti-Aggregation Formula (AAF) in Rabbits

PurposeWet age-related macular degeneration (AMD) is a blinding retinal disease. Monthly intravitreal anti-VEGF antibody injections of bevacizumab (off-label) and ranibizumab (FDA approved) are the standard of care. Antibody aggregation may interfere with ocular absorption/distribution. This study assessed topical delivery of dilute antibodies to the posterior segment of rabbit eyes using a novel anti-aggregation formula (AAF).MethodsBevacizumab, or biosimilar ranibizumab was diluted to 5 mg/ml in AAF. All rabbits were dosed twice daily. Substudy 1 rabbits (bevacizumab, 100 µl eye drops): Group 1 (bevacizumab/AAF, n = 6); Group 2 (bevacizumab/PBS, n = 7) and Vehicle control (AAF, n = 1). Substudy 2 rabbits (ranibizumab biosimilar/AAF, 50 µl eye drops): (ranibizumab biosimilar/AAF, n = 8). At 14.5 days, serum was drawn from rabbits. Aqueous, vitreous and retina samples were recovered from eyes and placed into AAF aliquots. Tissue analyzed using AAF as diluent.ResultsBevacizumab in AAF permeated/accumulated in rabbit aqueous, vitreous and retina 10 times more, than when diluted in PBS. AAF/0.1% hyaluronic acid eye drops, dosed twice daily, provided mean tissue concentrations (ng/g) in retina (29.50), aqueous (12.34), vitreous (3.46), and serum (0.28 ng/ml). Additionally, the highest concentration (ng/g) of ranibizumab biosimilar was present in the retina (18.0), followed by aqueous (7.82) and vitreous (1.47). Serum concentration was negligible (< 0.04 ng/ml). No irritation was observed throughout the studies.ConclusionsBevacizumab and ranibizumab, in an AAF diluent eye drop, can be delivered to the retina, by the twice daily dosing of a low concentration mAb formulation. This may prove to be an adjunct to intravitreal injections.

Pharmacokinetic profile and physiological effects of oral and compounded intravenous gabapentin in goats

ObjectiveTo determine the pharmacokinetics and physiological effects following oral and intravenous (IV) administration of gabapentin in goats. Study designProspective, crossover study with a 3 week washout period between treatments. AnimalsA total of eight healthy, client-owned, female goats. MethodsGabapentin (10 mg kg–1) was administered to goats either orally or IV. Gabapentin concentrations were measured in serum samples collected 0–96 hours post-administration using liquid chromatography–quadrupole time-of-flight mass spectrometry. Heart rate, respiratory rate, blood pressure and temperature were recorded before and throughout the study. Correlations of the mean serum concentrations of gabapentin to those of each physiological parameter were determined using the Pearson method. ResultsThe mean and standard deviation of oral bioavailability for gabapentin was 60.9 ± 11.2%. Maximum serum concentration of gabapentin was lower following oral (1.19 ± 0.29 μg mL–1) than after IV administration (59.76 ± 14.38 μg mL–1, p < 0.0001). Half-lives were longer following PO (8.18 ± 0.57 hours) than after IV administration (1.79 ± 0.06 hours, p < 0.0001). Time to maximum concentration was 6.86 ± 2.27 hours following oral administration. Heart rate was inversely correlated with serum gabapentin concentrations. Slight ataxia was observed in three animals, and one became recumbent following IV gabapentin. Conclusions and clinical relevanceGabapentin is well-absorbed following oral administration to goats but yielded significantly lower serum concentrations than the IV route. The longer half-life of gabapentin following oral than after IV administration may result from prolonged absorption throughout the caprine gastrointestinal tract. IV gabapentin may cause slight ataxia in some goats.

Determining the Effectiveness of Lactobacillus Casei in Camel Milk on Lipid and Sugar Parameters in Type 1 Diabetic Rats

Introduction: Nutritional interventions are one of the most effective methods of diabetes prevention and control. Along with usual treatments, camel milk has had positive effects on the blood sugar of diabetic patients. The present study was conducted with the aim of investigating the effect of lactobacillus casei present in camel milk on the sugar and lipid profile of type 1 diabetic rats. Methods: This was of an intervention study and carried out by an experimental trial method. 32 mice were randomly divided into four groups of eight. After making diabetic, the rats were gavage with 2cc of the product prepared for each group every other day. Evaluations (weight, serum concentrations of glucose, FBS, urea, creatinine, uric acid, LDL, HDL, TG, cholesterol, as well as liver enzymes AST, ALT, and ALP) were performed after 30 days of receiving gavage. In order to analyze the data, SPSS16 software was used. Results: The mean weight and serum concentration of LDL in the treatment group with standard and native Lactobacillus casei probiotics was significantly lower than the diabetic control group (P&lt;0.05) and the mean HDL in the treatment group with standard and native Lactobacillus casei probiotics was higher than the diabetic control group (P&lt;0.05), but there was no significant difference between the native Lactobacillus casei probiotic group and the standard. Urea, uric acid, FBS, Cr, TG, cholesterol, AST, ALT and ALP was not significantly different between the standard and native Lactobacillus casei probiotic group and the diabetic control one (P&gt;0.05). Conclusion: It seems that lactobacillus casei probiotics from camel milk may be able to improve weight loss and improve lipid profile (increase in HDL, decrease in LDL and LDL/HDL ratio) in type 1 diabetic rats, which requires more extensive studies in this field.

The impact of singing on estrogen and progesterone release among female

Scientific studies have suggested that singing can have positive effect on people’s health. (NAFME, 2012). John Daniel Scott, has cited that people who sing are more likely to be happy because singing elevates the level of neurotransmitters which is associated with pleasure and wellbeing. Most studies on the biological effect of music has resolved around studies involving brain mapping and physiological parameters such as heart rate, blood pressure, through production of messengers such as hormones, cytokines and proteins, music elicit biological responses to stress, emotions and immune functions. Hormone certainly prove necessary for proper physiological growth and development. This study is therefore to know the influence of singing on female sex hormone release which has variety of effects on both sexual organs and diverse target tissues. This research study will be a cross sectional and controlled investigative study. Hormone will be assayed with ELIZA technique and its secretion will be determined by its concentration in the blood. The study will be carried out with a total of thirty female choral singers, grouped into three A, B, C, each group will comprise of ten subjects, using group C as control. Blood sample will collect from each group at pre and post ovulation phase of their menstrual cycle, before and after singing while the control group will not be involved in singing. The mean serum concentration in all group will be compared with group C which serve as control group.

Relationship between brain-derived neurotrophic factor and mild to moderate cognitive impairment in the older Mexican population

BackgroundMild–moderate cognitive impairment is a frequent pathology in the adult population. It is important to explore early expression biomarkers that contribute to early detection and benefit the prognostic outlook. Brain-derived neurotrophic factor (BDNF) is an essential regulator of synaptic plasticity, neuronal survival, and differentiation, and even a critical molecular target for drug development in neurological disorders. It is crucial to carry out studies in the early stages that better clarify the landscape of BDNF. ObjectiveTo compare the serum levels of BDNF in healthy adult patients and those with mild to moderate cognitive impairment. Materials and methodsA casecontrol study in patients over 55- years with cognitive impairment, obtained by the MMSE® and MoCA® screening scales. A total of 191 patients, 102 patients with cognitive impairment (cases) and 89 healthy ones (controls) participated in the study. Blood samples were collected to obtain serum, with the determination of BDNF concentrations. For differences in BDNF concentrations, a one-way analysis of variance was used. The significance level of p<.05. ResultsThe mean serum concentration of BDNF in the case group was 277.68±75.09 vs. the control group, where the concentration was 354.97±66.06 pg/ml (p=.001). ConclusionsThere is an association between decreased BDNF levels and mild and moderate cognitive impairment in our study population.

Serum Zinc and Copper Levels in Children with Thalassemia Major

Background: Thalassemia is a frequent hereditary genetic with different clinical manifestations from mild to severe based on its genetic. Beta thalassemia major is the worse form of this disease caused by decreased or absent beta globin chains of hemoglobin. Regular blood transfusion is the main aim leads to iron overload and deposition of iron in different organs.Objectives: To determine different serum distribution levels and correlation of copper and zinc in transfusion dependent thalassemia patients Material and Methods: This was a descriptive cross-sectional study in which a non-probability convenient sampling technique was used for sample collection. This study was conducted in KPK in a total of 137 patients, who were diagnosed cases of thalassemia major by hemoglobin electrophoresis, enzyme linked immunosorbent assay (ELISA) method and receiving iron and folate therapy. SPSS version 22 was used and Pearson's correlation coefficient was applied. P-value 0.05 was considered significant.Results: In this study mean age was 6.7±3.49 years. 77 (56%) percent children were male while 64 (44%) children were female. Mean hemoglobin (Hb) level was 7.43±1.3 gm/dl. Mean SGPT score was 26.28 ± 7.51. Mean blood urea was 21.10 ± 8.49 mmol/l while mean serum creatinine level was 0.56 ± 0.26 mg/dl. Mean serum zinc level was 13.36 ± 11.12mg/dl while mean serum copper level was 1.21± 0.60 mg/dl and mean serum ferritin level was 6682 ± 533 Ug/l.Conclusion: This study showed hypozincemia in thalassemia major patients, but copper deficit was not present. There was no substantial variance between serum ferritin level and mean serum concentration of zinc and copper in this study. Ancillary assessments in this respect is recommended. Keywords: Copper, Thalassemia, Zinc

Smoke Signals: Unraveling the Link between Cigarette Smoking and Serum Liver Markers

Introduction: Cigarette smoking is a major cause of global mortality and morbidity. It exposes the body to many harmful substances, such as cytotoxic, carcinogenic and free radicals, that can damage various organs. This study aims to investigate the effects of different levels of tobacco exposure on liver tissue, by measuring some serum biochemical markers of liver function.&#x0D; Materials and Methods: The project conducted at T.N.M.C Mumbai from January to December 2021 involved 60 male participants (18–35 years old), divided into smokers (30) and non-smokers (30). Smokers had varying smoking durations (1-5 years). Excluded participants with diseases affecting liver enzymes. Groups were age-matched for analysis. Smokers defined as those smoking &gt;20 cigarettes daily for &gt;1 month. Collected 5.0 ml venous blood, processed in heparinized tubes, and centrifuged for plasma separation. Enzymes SGOT, SGPT, ALP, Total Bilirubin, Direct Bilirubin were measured, and statistical analysis revealed significant differences.&#x0D; Results: In the study, age comparison between smokers and non-smokers showed no significant difference (p = 0.71). However, smokers exhibited significantly higher mean serum concentrations of SGOT and SGPT compared to non-smokers (p = 0.002 and p &lt; 0.0001, respectively). Smokers also had elevated levels of ALP and total bilirubin with mean differences of 16.3 IU/L and 0.392 mg/dl, supported by 95% confidence intervals (6.72, 26.18) and (0.28, 0.504) and p values of 0.003 and 0.0004, respectively. No significant difference was observed in direct bilirubin levels (mean difference: 0.084 mg/dl, 95% CI: 0.065, 0.103, p = 0.191)&#x0D; Conclusion: In summary, the study suggests a correlation between smoking and elevated serum levels of liver enzymes and damage markers, indicating a potential adverse impact on liver function and increased susceptibility to liver diseases.

Vitamin D Deficiency in Advanced Laryngeal Cancer and its Association with Pharyngocutaneous Fistula Following Total Laryngectomy.

Nutritional factors in developing some malignancies have been investigated recently. In this study, we evaluated the role of vitamin D in advanced laryngeal cancer and its association with the development of pharyngocutaneous fistula (PCF) following total laryngectomy. A cross-sectional, case-control study was conducted. Fifty-five patients with advanced laryngeal cancer referred for total laryngectomy were included. We also considered 55 healthy individuals after matching age and sex as a control group. Serum levels of 25(OH)D3 were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The association of serum 25(OH)D3 with PCF following total laryngectomy was also determined. Vitamin D was significantly lower in patients with advanced laryngeal cancer than in the control group (p < 0.001). Moreover, our results showed that a mean serum concentration of 25(OH)D3 in patients with PCF was significantly lower than in patients without PCF (p < 0.001). Vitamin D deficiency is highly prevalent in advanced laryngeal cancer, most pronounced in those who develop a PFC following total laryngectomy.

UGT1A4*3 polymorphism influences serum concentration and therapeutic effect of lamotrigine for epilepsy treatment: A meta-analysis.

Lamotrigine as a broad-spectrum antiepileptic drug, is widely applied and its clinical efficacy is highly recognized. However, significant differences are observed in blood drug concentration of lamotrigine among individuals, which may have an impact on its efficacy. UGT1A4 is the main metabolic enzyme. However, it was inconsistent for the influence of UGT1A4 genetic polymorphism on concentration and efficacy of lamotrigine therapy. This study aimed to evaluate the influences of UGT1A4*3 genetic polymorphisms on lamotrigine concentration and therapeutic effect through meta-analysis. The literature search was conducted in Medline, Embase, PubMed, Web of Science, Wan Fang Database, China National Knowledge Infrastructure, China Science and Technology Journal Database until January 2024. The primary outcome included the mean serum concentration, concentration-to-dose-ratio by body weight (CDR), or efficacy related to different UGT1A4*3 genotype for lamotrigine therapy. Data were collected to access the Mean Difference or odds ratio with 95% confidence interval. Meta-analysis was performed by RevMan 5.2. A total of eleven studies were enrolled. The meta-analysis for mean serum concentration of lamotrigine showed no significant difference between patients carrying TT genotypes and TG and GG genotypes group (MD: 0.12, 95% [-0.35, 0.58], P = 0.62). There was significant difference in CDR (MD: 0.49, 95% [0.03, 0.94], P = 0.04) and therapeutic efficacy (OR: 7.18, 95% [4.01, 12.83], P<0.00001) of lamotrigine, however no significant difference was found in subgroup analysis of CDR of children (MD: 0.03, 95% [-0.35, 0.42], P = 0.87) between patients carrying TT genotypes and TG and GG genotypes group. Polymorphism of UGT1A4*3 influenced the CDR and therapeutic efficacy of lamotrigine for antiepileptic therapy. Genotype analysis provided reference for personalized medication in the future. However, more high-quality evidences are necessary for precise and definitive conclusion.

Evaluation of dermal toxicity and toxicokinetics of povidone‑iodine in Göttingen minipigs

BackgroundPovidone‑iodine (PVP-I) is an effective and commonly used broad-spectrum antiseptic; limited information exists around its long-term safety and impact on endocrine disruption. We assessed the dermal toxicity and toxicokinetics following a once-daily application of 7.5% (w/v) and 10% (w/v) PVP-I in Göttingen Minipigs® for up to 39 weeks. MethodsAn in vivo study was conducted in male (n = 27) and female (n = 27) minipigs. Animals were randomized into untreated control, 7.5% and 10% PVP-I, and matching vehicle treatment groups. Animals were assessed for general in-life measurements, including skin irritation and organ weights. Serum samples were analyzed for PVP, total iodine, triiodothyronine [T3], thyroxine [T4], thyroid stimulating hormone [TSH], and toxicokinetic parameters. ResultsNeither 7.5% nor 10% PVP-I affected general in-life measurements. Increased mean thyroid gland absolute weights were noted with 7.5% and 10% PVP-I. Serum levels of PVP, T3, T4, and TSH in the 7.5% and 10% PVP-I treatment group animals were similar to those in vehicle treatment group animals. Mean total serum iodine concentration was 52- and 13-fold higher with 7.5% and 10% PVP-I, respectively, vs respective vehicle treatments. There was no dose-dependent increase in mean maximum serum concentration and area under the curve from 0 to 24 h for PVP, T3, T4, and TSH, nor accumulation of PVP, T3, T4, or TSH in the study. ConclusionOnce-daily dermal application of 7.5% and 10% PVP-I for up to 39 weeks was safe and well tolerated in Göttingen Minipigs® and was not associated with skin irritation, thyroid dysfunction, or endocrine disruption. As the anatomy and physiology of the minipig skin closely resembles that of human skin, the findings of this study suggest that 7.5% and 10% PVP-I may be translated into antimicrobial benefits for humans without the risk of endocrine disruption.

Bioavailability and Antihyperglycemic Effect of Four Glibenclamide Tablets: A Comparative Study

This study compared the bioavailability and antihyperglycemic effect of 5 mg glibenclamide tablets available in Sudan. Nine healthy subjects were given a 5 mg dose of either micronized glibenclamide tablets (Euglucon®) or conventional non-micronized glibenclamide tablets (locally manufactured items). Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours and analyzed for glucose concentrations. The maximum mean serum concentration of the drug (Cmax) and the mean time to maximum serum concentration (Tmax) were calculated, and the area under the concentration versus time curve (AUC) and the drug clearance (Cl) were also recorded. The mean glucose concentration was also determined in different time intervals. The results show no significant difference in the mean Tmax between the tested items. However, the mean Cmax is significantly higher (p 0.001) when the non-micronized tablets are taken (456 ng/mL) rather than the micronized tablets (291 ng/mL). Similarly, the mean AUC0-8h is significantly higher (p 0.001) with the non-micronized tablets (1915 ng/mL.h) than with the micronized tablets (1163 ng/mL.h). After 8 hours, the subjects in the micronized group had a drug clearance of 0.0430 L/Kg.h, and a clearance of 0.0260 L/Kg.h was recorded in the unmicronized group. Both tablets lower the mean glucose concentrations of the nine volunteers after 8 hours, 99 mg/dL for micronized tablets and 98 mg/dL for non-micronized tablets. Overall, the non-micronized glibenclamide tablet used in this study similarly lowered the glucose concentrations in healthy volunteer subjects to that of imported micronized glibenclamide tablets.

Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis)

IntroductionCannabinoids are increasingly popular in human and veterinary medicine and have been studied as an alternative treatment for a wide range of disorders. The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol (CBD)-/cannabidiolic acid (CBDA)-rich hemp oil (CBD/ArHO) in juvenile cynomolgus macaques (Macaca fascicularis).MethodsAfter a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered (n = 4 per dose) once daily for 14 days and blood was collected at 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, and 24-h, and on Days 7 and 14, to quantify serum cannabinoid concentrations by high-performance liquid chromatography–tandem mass spectrometry. Serum biochemistries and complete blood counts were performed on Days 0, 1, and 14.ResultsThe maximum mean serum concentration (Cmax) of CBDA was 28.6–36.2 times that of CBD at 4 and 8 mg/kg. At 8 mg/kg, the Cmax of CBD was 1.4 times higher (p = 0.0721), and CBDA was significantly 1.8 times higher (p = 0.0361), than at 4 mg/kg. The maximum mean serum concentration of ∆9-tetrahydrocannabinol (THC) was 4.80 ng/mL at 8 mg/kg. Changes in serum biochemistries and complete blood counts over time were not clinically significant.DiscussionGiven the low serum CBD concentrations, the doses and frequency used in this study may be insufficient for a therapeutic effect of CBD in particular; therefore, clinical studies are needed to determine the therapeutic dose of CBD and CBDA for macaques, which may differ based on the disorder targeted.