Blood Levels Research Articles

Prestin in Human Perilymph, Cerebrospinal Fluid, and Blood as a Biomarker for Hearing Loss.

Determining the concentration of prestin in human blood, cerebrospinal fluid (CSF), and perilymph (PL), and evaluating its suitability as a clinical biomarker for sensori-neural hearing loss (SNHL). Human blood, CSF, and PL samples were intraoperatively collected from 42 patients with tumors of the internal auditory canal or with intracochlear tumors undergoing translabyrinthine or middle fossa tumor removal. Prestin concentration was measured using enzyme-linked immunosorbent assay and linear regression analyses were performed to investigate its associations with audiological as well as vestibular test results. Tertiary referral center. The median prestin concentration in blood samples of the 42 study participants (26 women, mean ± standard deviation age, 52.7 ± 12.5 years) was 1.32 (interquartile range, IQR, 0.71-1.99) ng/mL. CSF prestin levels were significantly higher with 4.73 (IQR, 2.45-14.03) ng/mL (P = .005). With 84.74 (IQR, 38.95-122.00) ng/mL, PL prestin concentration was significantly higher compared to blood (P = .01) and CSF (P = .03) levels. Linear regression analyses showed significant associations of CSF prestin concentration with preoperative hearing levels (pure-tone average and word recognition; P = .008, R2 = 0.1894; P = .03, R2 = 0.1857), but no correlations with blood or PL levels. This study's findings highlight the volatile nature of prestin levels and provide the first insights into this potential biomarker's concentrations in body fluids apart from blood. Future investigations should comprehensively assess human prestin levels with different etiologies of SNHL, prestin's natural homeostasis and systemic circulation, and its temporal dynamics after cochlear trauma. Finally, clinically approved detection kits for prestin are urgently required prior to considering a potential translational implementation of this diagnostic technique.

The role of inflammation and oxidative stress in the pathophysiology of depressions: time to consider vitamin C deficiency

Depression is on the rise and medication does not always provide satisfactory relief. This raises the question of a treatment gap that has not yet been (sufficiently) addressed. Inflammation and oxidative stress play an important pathophysiological role, which also leads to a deficiency of antioxidants such as vitamin C. This perspective mini-review reflects the results of a PubMed search combining the search terms depression with inflammation, oxidative stress and vitamin C. Vitamin C is an important antioxidant and co-factor for many neuronal metabolic and epigenetic pathways, and a deficiency is associated with depression and cognitive disorders. Inadequate vitamin C blood levels that do not yet result in somatic symptoms may induce neuropsychiatric scurvy, which is associated with increased neuroinflammation and characterized by depression and cognitive impairment. Experimental studies show that vitamin C has multifactorial effects on metabolic pathways relevant to depression. Treatment of vitamin C deficiency, which is more common than appreciated, should be considered in the management of depressed patients. Further studies should investigate whether the pharmacological administration of vitamin C has additional effects beyond the correction of deficiency.

Genetic analysis of efficiency-related traits in Boer x Central Highland goats.

This study aimed to identify important non-genetic factors and estimate genetic parameters for efficiency-related traits in Boer x Central Highland goats. The genetic parameters were estimated using the Average Information Restricted Maximum Likelihood algorithm using the WOMBAT program fitting animal model. The least-squares means for growth efficiency from birth to 3 months (GE1), 3-6 months (GE2), 6-12 months (GE3), relative growth rate from birth to 3 months (RGR1), 3-6 months (RGR2) and 6-12 month (RGR3) were 294.0 ± 5.06, 36.6 ± 1.20, 44.9 ± 1.81, 1.46 ± 0.01, 0.32 ± 0.01 and 0.19 ± 0.01, respectively. Birth type, blood level, sex of the kid, and year of kidding had a sizable effect on efficiency-related traits. About 18, 3.0, 23, 20, and 12% of the phenotypic variation in GE2, GE3, RGR1, RGR2, and RGR3 was explained by the direct additive genetic effect. Except for RGR3, all investigated traits were under the influence of maternal genetic effect, and maternal heritability ranged from 0.09 to 0.17. The total heritability estimate depicts that slow genetic progress would be expected from selection. Nevertheless, even with this level of heritability, selection for efficiency-related traits would improve the efficiency of chevon production as these traits are economically important traits. Nearly six-months of age was when farmers sold Boer crossbred goats. Therefore, improving the growth efficiency till the marketing age (GE2) in such a scenario could increase the production efficiency.

Neurocognitive, Clinical and Reelin Activity in Rehabilitation Using Neurofeedback Therapy in Patients with Schizophrenia

Introduction: Reelin is a neuropeptide responsible for the migration and positioning of pyramidal neurons, interneurons, and Purkinje cells. In adulthood, it still supports neuroplasticity, especially dendritic spines formation and glutamatergic neurotransmission. Genetic studies have confirmed the involvement of reelin system failure in the etiopathogenesis of mental diseases, including schizophrenia. Given the role of reelin in brain cytoarchitectonics and the regularly observed reduction in its activity in prefrontal areas in cases of schizophrenia, dysfunction of the reelin pathway fits the neurodevelopmental hypothesis of schizophrenia, both as a biochemical predisposition and/or the ultimate trigger of psychosis and as a biosocial factor determining the clinical course, and finally, as a potential target for disease monitoring and treatment. Aim: The purpose of this study was to examine associations of the reelin blood level with clinical and neurocognitive parameters during an intensive, structured neurofeedback therapy of patients with schizophrenia. Methods: Thirty-seven male patients with paranoid schizophrenia were randomly divided into two groups: a group with 3-month neurofeedback as an add-on to ongoing antipsychotic treatment (NF, N18), and a control group with standard social support and antipsychotic treatment (CON, N19). The reelin serum concentration, clinical and neurocognitive tests were compared between the groups. Results: After 3-month trial (T2), the reelin serum level increased in the NF group vs. the CON group. The negative and general symptoms of PANSS (Positive and Negative Syndrome Scale) were reduced significantly more in the NF group at T2, and the d2 (d2 Sustained Attention Test) and BCIS (Beck Cognitive Insight Scale) scores improved only in the NF group. The AIS scores improved more dynamically in the NF group, but not enough to differentiate them from the CON group at T2. Conclusions: The clinical and neurocognitive improvement within the 3-month NF add-on therapy trial was associated with a significant increase of reelin serum level in schizophrenia patients.

Effect of early post-hematopoietic stem cell transplant tacrolimus concentration on transplant outcomes in pediatric recipients: One facility’s ten-year experience of immunosuppression with tacrolimus

Acute graft-versus-host disease (GVHD) is a common life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), ranking as the second leading cause of death among recipients, surpassed only by disease relapse. Tacrolimus is commonly used for GVHD prophylaxis, but achieving therapeutic blood levels is challenging, particularly in pediatrics, due to the narrow therapeutic window and the high interindividual variability. The retrospective study conducted at IRCCS “Burlo Garofolo” in Italy aimed to assess the impact of early post-HSCT tacrolimus levels on transplant-related outcomes in pediatric recipients. The population pharmacokinetic model (POP/PK) was set up to describe tacrolimus pharmacokinetics. Elevated tacrolimus (>12–15 ng/ml) levels within the initial weeks post-HSCT are associated with reduced post-transplant infections (p < 0.0001) and decreased incidence of early transplant-related events (p < 0.01), including a lower incidence of acute GVHD (p < 0.05 on day 0). High tacrolimus exposure can lead to an increased risk of chronic GVHD (p < 0.0001) and reduced overall survival (p < 0.01). Personalized dosing and therapeutic monitoring of tacrolimus are crucial to ensure optimal outcomes. POP/PK could help achieve this goal, giving us a model by which we can balance immunosuppression while looking at the patient’s general well-being and providing the necessary treatment.

Safety, Pharmacokinetics, and Pharmacodynamics of the New Aldose Reductase Inhibitor Govorestat (AT-007) After a Single and Multiple Doses in Participants in a Phase 1/2 Study.

In classic galactosemia (CG) patients, aldose reductase (AR) converts galactose to galactitol. In a phase 1/2, placebo-controlled study (NCT04117711), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of govorestat were evaluated after single and multiple ascending doses (0.5-40 mg/kg) in healthy adults (n = 81) and CG patients (n = 14). Levels of govorestat in plasma and cerebrospinal fluid (CSF) and blood levels of galactitol, galactose, and galactose-1-phosphate (Gal-1p) were measured for population PK and PK/PD analyses. Govorestat was well tolerated. Adverse event frequency was comparable between placebo and govorestat. Govorestat PK displayed a 2-compartment model with sequential zero- and first-order absorption, and no effect of demographic factors. Multiple-dose PK of govorestat was linear in the 0.5-40 mg/kg range, and CSF levels increased dose dependently. Elimination half-life was ∼10 h. PK/PD modeling supported once-daily dosing. Change from baseline in galactitol was -15% ± 9% with placebo and -19% ± 10%, -46% ± 4%, and -51% ± 5% with govorestat 5, 20, and 40 mg/kg, respectively, thus was similar for 20 and 40 mg/kg. Govorestat did not affect galactose or Gal-1p levels. In conclusion, govorestat displayed a favorable safety, PK, and PD profile in humans, and reduced galactitol levels in the same magnitude (∼50%) as in a rat model of CG that demonstrated an efficacy benefit on neurological, behavioral, and ocular outcomes.

Andrographis paniculata Ethanolic Extract Improved Doxorubicin-induced Cardiac Inflammation, Alterations in Liver Function Parameters and Anemia

Background: Doxorubicin (DOX), an efficacious chemotherapy drug is compromised by cardiotoxicity, myelosuppression, and hepatotoxicity. Due to the limited success of current treatments for DOX toxicity, there is a pressing need to explore alternative medical interventions, particularly from plant sources. This study was conducted to investigate the potential protective effect of ethanolic extract of Andrographis paniculata leaves (EEAP) against DOX-induced cardiac inflammation, liver toxicity, and anemia.Materials and methods: Sprague-Dawley rats were intraperitoneally injected with DOX at a total dose of 16 mg/kgBW. EEAP was administered orally for 4 weeks at doses of 125, 250, and 500 mg/kgBW/day according to the assigned treatment groups. The mRNA expression levels of interleukin-1β (IL-1β) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) in the heart tissue, along with the concentrations of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and calcium level were examined. Additionally, the hematological parameters (including hematocrit, hemoglobin and red blood cells (RBCs)), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels in blood were also analyzed.Results: EEAP dose-dependently decreased the mRNA expressions of IL-1β (p&lt;0.05), tended to decrease mRNA expression of NLRP3 and the concentrations of NFκB and calcium in heart tissue compared with the DOX-only group. Additionally, EEAP dose-dependently decreased ALP values (p&lt;0.0001) and tended to improve hematological parameters, as well as AST and MDA levels in serum.Conclusion: This extract may prevent DOX-induced cardiac inflammation, anemia, and hepatotoxicity. However, further studies are needed to confirm these findings, including the efficacy profile of the extract in cancer rats treated with DOX.Keywords: doxorubicin, Andrographis paniculata, inflammation, anemia, hepatotoxicity, herbal medicine

A Novel Method for the Early Detection of Single Circulating, Metastatic and Self-Seeding Cancer Cells in Orthotopic Breast Cancer Mouse Models

Background: Metastasis is the main cause of cancer-related deaths, but efficient targeted therapies against metastasis are still missing. Major gaps exist in our understanding of the metastatic cascade, as existing methods cannot combine sensitivity, robustness, and practicality to dissect cancer progression. Addressing this issue requires improved strategies to distinguish early metastatic colonization from metastatic outgrowth. Methods: Luciferase-labelled MDA-MB-231, MCF7, and 4T1 breast cancer cells were spiked into samples from tumour-naïve mice to establish the limit of detection for disseminated tumour cells. Luciferase-labelled breast cancer cells (±unlabelled cancer-associated fibroblasts; CAFs) were orthotopically implanted in immunocompromised mice. An ex vivo luciferase assay was used to quantify tumour cell dissemination. Results: In vitro luciferase assay confirmed a linear and positive correlation between cancer cell numbers and the bioluminescence detected at single cell level in blood, brain, lung, liver, and mammary fat pad samples. Remarkably, single luciferase-labelled cancer cells were detectable in all of these sites, as the bioluminescence quantified in the analysed samples was substantially higher than background levels. Ex vivo, circulating tumour cells, metastasis, and tumour self-seeding were detected in all samples from animals implanted with highly metastatic luciferase-labelled MDA-MB-231 cells. In turn, detection of poorly metastatic luciferase-labelled MCF7 cells was scarce but significantly enhanced upon co-implantation with CAFs as early as 20 days after the experiment was initiated. Conclusions: These results demonstrate the feasibility of using an ultrasensitive luciferase-based method to dissect the mechanisms of early metastatic colonization to improving the development of antimetastatic therapies.

Testosterone and neurobehavioral outcomes in special operations forces military with multiple mild traumatic brain injury.

U.S. Special Operations Forces (SOF) are at increased risk of multiple mild traumatic brain injury (mmTBI). Testosterone was prescribed for several participants in a VA program designed to address sequelae of mmTBI for SOF. To determine testosterone prevalence in the Palo Alto VA Intensive Evaluation and Treatment Program (IETP) and observe for association between testosterone and neurobehavioral outcomes. A retrospective cohort study included patients in the Palo Alto VA IETP. Sociodemographic data, testosterone blood levels, and neurobehavioral outcomes were collected from medical records. 55 IETP participants were included: six were testosterone users; the rest were classified as non-users. Testosterone use in this population is 11%, higher than reported national averages in the U.S. Of the 6 testosterone users, 2 (33%) had a formal diagnosis of hypogonadism prior to initiation of testosterone. Neurobehavioral outcome scores between testosterone users and non-users failed to show statistically significant differences, except for the PROMIS pain score, which was higher in the testosterone user population. The current study did not find an association between mmTBI, testosterone use, or testosterone level and neurobehavioral outcomes. This study highlights a need to further examine the relationship between hypogonadism, mmTBI, SOF culture around testosterone, and the effects of testosterone use in this population.

Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85–80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p &lt; 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p &lt; 0.001, ηp2 = 0.581) and plasma (p &lt; 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85–80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p &lt; 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p &lt; 0.001, ηp2 = 0.581) and plasma (p &lt; 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Lead in umbilical cord blood and associated factors in Casablanca Morocco: A preliminary results

BackgroundLead is the most common toxic metal to which Moroccans are exposed. Given the susceptibility of the fetus to lead, it is crucial to assess prenatal lead exposure. However, in Morocco, no study has assessed prenatal exposure to lead. The main goals of the present study are to determine lead concentration in umbilical cord blood and identify risk factors for prenatal lead exposure in Casablanca, Morocco. MethodsTo achieve these purposes, 87 cord blood lead samples were collected from mothers-baby pairs from January to December 2019. Indeed, a structured questionnaire was used to collect socio-demographic characteristics, obstetric data, leisure, cultural habits, and environmental information. Cord blood lead level was analyzed by inductively coupled plasma-mass spectrometry. ResultsThe median lead concentration was 4.902 µg/dl with a minimum and maximum of 0.833 µg/dl and 23.593 µg/dl, respectively. A high proportion of the newborns (65.52 %) had cord blood lead levels above the Centers for Disease Control (CDC) allowable threshold limit (3.5 µg/dl). Statistical analysis was performed to assess the association between blood levels and the above factors. Lead levels in cord blood were significantly associated with the maternal educational level, anemia history, delivery mode, passive smoking during pregnancy as well as with the frequency of consumption of tea. ConclusionThis study provides the first data on lead levels in newborns. Cord blood lead levels were high in the majority of the participants, these results reinforce the need to establish health surveillance programs in Morocco.

Case Report: The Effect of Ajwa Date Consumption on Total Cholesterol Levels in Perimenopausal Women

Based on the 2016 Riskesdas, the prevalence of high cholesterol in Indonesia among women aged 35-59 years was 52.9%, and among those aged ≥60 years, it was 58.7%. According to provincial data, the highest percentage of patients with high cholesterol levels at Posbindu and FKTP in Indonesia was in West Papua Province, reaching up to 70%. The concentration of cholesterol levels in women's blood tends to increase with age, particularly for those over 40 years old, due to hormonal factors, especially the decrease in estrogen production and function. The decline in estrogen levels leads to an increase in lipids or total cholesterol, resulting in changes in body fat composition associated with hypercholesterolemia. This case report aims to investigate the impact of consuming Ajwa dates on the total cholesterol levels of perimenopausal women. Results: Ajwa dates contain higher polyphenol concentrations with an impressive nutritional profile that enhances blood lipoproteins. Additionally, dates can increase estrogen levels due to the estradiol and estrone present in their pollen. Several experimental studies have shown a significant difference in total cholesterol levels in subjects before and after consuming Ajwa dates. Conclusion: There is a notable difference in total cholesterol levels before and after the administration of Ajwa dates.

Atherogenic Effect of Homocysteine, a Biomarker of Inflammation and Its Treatment

AbstractHyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B6 and vitamin B12 folic acid (vitamin B9). Causes of HHcy include deficiency of vitamins B6, B9, and B12, genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1β, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-β), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B6, and vitamin B12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B6, vitamin B12, omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.

Effect of concomitant use of yokukansan on steady-state blood concentrations of donepezil and risperidone in real-world clinical practice.

Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting. A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co-treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high-performance liquid chromatography-tandem mass spectrometry and compared before and after the 8-week administration of yokukansan. The plasma concentrations of donepezil and its metabolites (6-O-desmethyl-donepezil, 5-O-desmethyl-donepezil, and donepezil-N-oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8-week treatment with yokukansan. The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady-state blood levels of donepezil and risperidone in patients with dementia or schizophrenia.

Hyperosmolarity in children with hyperammonemia: a risk of brain herniation at the start of renal replacement therapy.

Renal replacement therapy (RRT) is used in hyperammonemia to reduce the concentration of ammonia in the blood. In the case of plasma hyperosmolarity, RRT can also rapidly decrease plasma osmolarity, which may increase cerebral edema in these patients and favor the occurrence of brain herniation. We conducted a retrospective clinical study in a tertiary care university-affiliated hospital. All patients admitted in a Pediatric Intensive Care Unit (PICU), less than 18 years old with ammonemia >150 µmol/L and who underwent RRT between January 2015 and June 2023 were included. We collected data on plasma osmolarity levels, osmolar gap and blood ammonia levels before and during RRT. Eleven patients were included (10 with acute liver failure and 1 with a urea cycle disorders). Their mean age was 36.2 months. Before RRT, the median highest measured osmolarity was 320 (305-324) mOsm/L, whereas the median calculated osmolarity was 303 (293-314) mOsm/L, corresponding to an osmolar gap of 14 mOsm/L. Ammonia blood level over 400 µmol/L are significantly associated with higher plasma osmolarity (P-Value <0.001). In one case, a patient had a brain herniation episode after a quick osmolar drop. This episode was reversed by the administration of hyperosmolar agents and the temporary suspension of RRT. This study highlights the hyperosmolarity and high osmolar gap that occur in children with hyperammonemia. A careful monitoring and control of plasma osmolarity evolution may alert clinician on the risk of occurrence of neurological complication such as brain herniation.

Atherogenic Effect of Homocysteine, a Biomarker of Inflammation and Its Treatment

AbstractHyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B6 and vitamin B12 folic acid (vitamin B9). Causes of HHcy include deficiency of vitamins B6, B9, and B12, genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1β, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-β), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B6, and vitamin B12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B6, vitamin B12, omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.

Frequency of ABO and RhD Blood Groups in Patients with Celiac Disease

Celiac disease (CD) is a popular autoimmune disorder induced by gluten-containing foods and other environmental, and genetic factors. Every individual's red blood cell expresses over two million ABO blood-type antigens. Furthermore, the stomach and small intestine are major expression sites for the ABH antigens. This study was intended to assess the distribution of ABO and Rh blood types in Libyan patients with celiac disease as well as compare between CD and healthy control groups regarding complete blood count parameters. Samples from 250 CD patients and 45 healthy control groups represented by 80 males (27.1%) and 215 females (72.9%) were enrolled in the study. The samples of CD were collected from patients who attended the gastroenterology outpatient clinic at Tripoli University Hospital (TUH) for follow-up. Two hundred and fifty blood samples were serologically screened for ABO, and Rh antigens using a tube agglutination test. Another group of healthy subjects (n = 45) and CD patients (n = 45) were analyzed for CBC test. The findings showed that the most observed ABO blood group among celiac patients was blood group O 129 (51.6%), followed by blood group A 80 (32%), and Rh-positive 222 (88.8%). Furthermore, the heritable proportion was 33%, with 21% classified as first-degree and 12% as second-degree hereditary. Additionally, the result of the independent Sample (T) test to compare RBCs, HGB, HCT, and NUT levels in blood between CD patients and healthy control showed that there were significant differences in the RBCs, HGB, and HCT counts with p-value = 0.034, &lt;0.001, and &lt;0.001 respectively. In contrast, Mann-Whitney U test results revealed significant differences in the PLT, MCV, MCH, and MCHC counts with p-value = &lt;0.001, and for LYM with p-value = 0.003. Future studies on these simple inflammatory markers can guide us in predicting the diagnosis and prognosis.

Frequency of ABO and RhD Blood Groups in Patients with Celiac Disease

Celiac disease (CD) is a popular autoimmune disorder induced by gluten-containing foods and other environmental, and genetic factors. Every individual's red blood cell expresses over two million ABO blood-type antigens. Furthermore, the stomach and small intestine are major expression sites for the ABH antigens. This study was intended to assess the distribution of ABO and Rh blood types in Libyan patients with celiac disease as well as compare between CD and healthy control groups regarding complete blood count parameters. Samples from 250 CD patients and 45 healthy control groups represented by 80 males (27.1%) and 215 females (72.9%) were enrolled in the study. The samples of CD were collected from patients who attended the gastroenterology outpatient clinic at Tripoli University Hospital (TUH) for follow-up. Two hundred and fifty blood samples were serologically screened for ABO, and Rh antigens using a tube agglutination test. Another group of healthy subjects (n = 45) and CD patients (n = 45) were analyzed for CBC test. The findings showed that the most observed ABO blood group among celiac patients was blood group O 129 (51.6%), followed by blood group A 80 (32%), and Rh-positive 222 (88.8%). Furthermore, the heritable proportion was 33%, with 21% classified as first-degree and 12% as second-degree hereditary. Additionally, the result of the independent Sample (T) test to compare RBCs, HGB, HCT, and NUT levels in blood between CD patients and healthy control showed that there were significant differences in the RBCs, HGB, and HCT counts with p-value = 0.034, &lt;0.001, and &lt;0.001 respectively. In contrast, Mann-Whitney U test results revealed significant differences in the PLT, MCV, MCH, and MCHC counts with p-value = &lt;0.001, and for LYM with p-value = 0.003. Future studies on these simple inflammatory markers can guide us in predicting the diagnosis and prognosis.

[Translated article] Survival Analysis and Prognostic Factors in a Case Series of 148 Cutaneous T-Cell Lymphomas

Background and ObjectiveCutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS) are rare lymphomas with varying prognoses. The aim of the study was to describe the survival of a cohort of patients with MF/SS and evaluate the prognostic factors impacting disease survival. Materials and MethodsAll cases of MF/SS diagnosed from 2008 through 2022 were retrospectively analyzed. The demographic variables, histological parameters, and analytical data were analyzed too. Progression-free survival (PFS) and disease-specific survival (DSS) were calculated. ResultsA total of 148 cases were included. A total of 121 (82%) and 27 cases were diagnosed with MF, and SS, respectively. A total of 37 patients (25%) experienced progression at some point disease progression. The median PFS and median DSS were 127 and 135 months, respectively. Age >60 years, diagnosis of SS, the presence of large cell transformation (LCT) at diagnosis, folliculotropism in early stages, high Ki-67 expression, the presence of the clonal T-cell receptor (TCR) in blood, elevated LDH and B2M levels, and advanced stages (IIB, IVA, T3, T4, N3/Nx) were associated with worse prognosis across the entire cohort. ConclusionsStage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis. LCT was the variable that most significantly impacted the patients’ survival and was closely associated with tumor skin involvement and stage IIB.