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1.
Pediatr Res ; 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38575692

ABSTRACT

BACKGROUND: Beta-thalassemia major (ß-TM) patients are more likely to experience blood glucose intolerance and to date; the blood markers that could evaluate this are debatable. So, this study aimed to assess the roles of glycated hemoglobin A1c (HbA1c) and fructosamine in evaluating glucose intolerance in children with ß-TM and figuring out role of insulin resistance in these patients. METHODS: One hundred children diagnosed with ß-TM and 100 age and sex-matched controls were enrolled. Fasting plasma glucose (FPG), 2-h post-prandial blood glucose (2-h PG), HbA1c, fructosamine, fasting insulin level (FINS), insulin resistance index (HOMA-IR), and insulin sensitivity index (HOMA-IS) were evaluated. RESULTS: FPG and 2-h PG revealed glucose intolerance in 51 patients (51%), 19 of them had diabetes mellitus. HbA1c, fructosamine, FINS, and HOMA-IR showed a high statistically significant increase in patients compared to controls, (P < 0.001). Results revealed fructosamine was more specific in detecting prediabetes state and more sensitive in identifying diabetes mellitus in our patients when compared to HbA1c. CONCLUSIONS: Despite controversies on HbA1c in children with ß-TM, it is still valuable in glucose intolerance detection. Fructosamine showed more sensitivity and specificity. Furthermore, insulin resistance was prevalent in children with ß-TM highlighting the necessity of regular glycemic state evaluation. IMPACT: Glucose intolerance is a common complication in beta thalassemia patients. Conflicting data was reported about the role of HbA1c and fructosamine in evaluating glucose intolerance in thalassemic patients. Fructosamine does not yet have a threshold that may be used to distinguish between patients who have diabetes mellitus and those who do not. Fructosamine was more specific in detecting blood glucose intolerance compared to HbA1c and was more sensitive for diagnosing diabetes mellitus. Insulin resistance was common in patients with beta-thalassemia and often present before the onset of overt diabetes.

2.
Pediatr Res ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39048669

ABSTRACT

BACKGROUND: Despite a well-known dose-dependent association between the risk of cardiac dysfunction and anthracycline, the risk of cardiac dysfunction for any given anthracycline dose varies between patients. So, we assessed CELF4 (rs1786814) gene polymorphism on anthracycline-related cardiotoxicity in childhood cancer survivors (CCS). METHODS: This comparative cross-sectional study included 53 CCS who had regular follow-up visits at the Pediatric Oncology Unit, Menoufia University Hospital. CELF4 (rs1786814) gene polymorphism and conventional and speckle-tracking Echocardiography were done for all survivors. RESULTS: Regarding CELF4 (rs1786814) genotypes, significant differences existed between the studied groups with a predominance of GG homozygous mutation. For Echocardiographic findings, the ejection fraction and end-systolic diameter compared to the control group, were significantly lower in the survivors group. Speckle- tracking Echocardiography showed a significant difference regarding (GLPS-A4C) and (GLPS-LAX), with no significant difference regarding (GLPS-A2C), (GLPS-Avg) and left atrium between the studied groups. Multivariate logistic regression analysis illustrated a statistically significant relation between cumulative anthracycline dose >300 mg/m2 and CLEF4 (rs1786814) genotypes (GG and GA) and the risk of cardiotoxicity with more significance in GG mutation. CONCLUSION: Early detection of ventricular dysfunction in CCS with subclinical cardiotoxicity with regular follow-up is promising before the development of life-threatening complications. IMPACT: Early detection of anthracycline-related cardiotoxicity in childhood cancer survivors (CCS) after finishing chemotherapy. CLEF4 (rs1786814) GG variant is more significant in CCS exposed to high-dose anthracycline. GLPS holds promise as an early predictor of late left ventricular dysfunction and subclinical cardiotoxicity in CCS.

3.
Pediatr Res ; 94(2): 668-675, 2023 08.
Article in English | MEDLINE | ID: mdl-36755189

ABSTRACT

BACKGROUND: We assessed serum concentrations of pancreatic stone protein (PSP), copeptin, and apolipoprotein A-V (APOA5) biomarkers for the diagnosis and prognosis of pediatric sepsis, a condition associated with high mortality. METHODS: This prospective study included 180 children admitted to the Pediatric Intensive Care Unit and 100 healthy controls at Menoufia University Hospital. Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality-2 (PIM2), and Pediatric Sequential Organ Failure Assessment (pSOFA) scores were calculated. Serum PSP, copeptin and APOA5 were measured once within 24 h of admission. RESULTS: PSP, copeptin, and APOA5 were significantly higher in the patients than in the controls (p < 0.001). PSP and copeptin were increased among children who required mechanical ventilation (MV), had multiple organ dysfunctions, and were non-survivors, but APOA5 was decreased in those children. Logistic regression analyses showed that high pSOFA, high PSP and copeptin, low APOA5, and use of MV were associated with mortality. The receiver operating characteristic revealed that the area under the curve (AUC) for APOA5, copeptin, and PSP (0.965, 0.960, and 0.868, respectively) demonstrated high sensitivity (96%, 94%, and 80%) for sepsis diagnosis. The AUC values for PSP, copeptin, and APOA5 were 0.709, 0.705, and 0.571, respectively, with sensitivities of 74%, 58%, and 58% for mortality prediction. CONCLUSIONS: PSP, copeptin, and APOA5 are promising diagnostic biomarkers for pediatric sepsis but inadequate predictors of mortality. IMPACT: Apolipoprotein A-V (APOA5), copeptin, and pancreatic stone protein (PSP) are acute-phase proteins with diagnostic value in evaluating critically ill pediatric patients with sepsis and detecting sepsis severity. PSP and copeptin had the power to discriminate non-survivors from survivors. APOA5 was less powerful than the other biomarkers in discriminating between survivors and non-survivors.


Subject(s)
Lithostathine , Sepsis , Humans , Child , Apolipoprotein A-V , Prospective Studies , Prognosis , Biomarkers , Sepsis/diagnosis , ROC Curve
4.
Pediatr Res ; 93(7): 1922-1926, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36774398

ABSTRACT

BACKGROUND: The risk of neurological complications is increased in children with sickle cell disease (SCD), such as silent cerebral infarction (SCI) and stroke. Brain-Derived Neurotrophic Factor (BDNF) is a nerve growth factor associated with elevated transcranial Doppler (TCD) velocities and increased risk of stroke in SCD patients. So, we assessed the BDNF level in children with SCD and its relation to neurological complication as silent stroke. METHODS: A comparative cross-sectional study was conducted on 40 patients with SCD, recruited from the Hematology Unit, Pediatric Department, Menoufia University Hospital, and 40 healthy children as controls. Laboratory investigations including BDNF were done. TCD was done for all patients and Magnetic Resonance Imaging (MRI) was done on high-risk patients. RESULTS: BDNF levels were significantly higher in children with SCD than in controls with a significant relation to TCD findings. There was a statistically significant diagnostic ability of BDNF in the prediction of SCD complications as its sensitivity was 89.5%, specificity (95% CI) was 80% with a cut-off point >0.69, AUC = 0.702, and p = 0.004). CONCLUSION: Serum BDNF levels were higher in sickle disease patients who had abnormal transcranial Doppler. BDNF had a significant diagnostic ability in the detection of SCD complications. IMPACT: Silent stroke is a very serious complication in children with sickle cell disease, so regular follow up should be every six months. BDNF is considered a potential biomarker for stroke risk prediction in patients unable to receive TCD.


Subject(s)
Anemia, Sickle Cell , Stroke , Humans , Child , Brain-Derived Neurotrophic Factor , Cross-Sectional Studies , Anemia, Sickle Cell/complications , Stroke/etiology , Stroke/complications , Ultrasonography, Doppler, Transcranial/adverse effects , Ultrasonography, Doppler, Transcranial/methods
5.
Eur J Pediatr ; 182(10): 4583-4593, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37542670

ABSTRACT

Malnutrition has adverse impacts on under-five children with pneumonia. The purpose of this study was to address the prevalence and impact of malnutrition on under-five years children with pneumonia, admitted to a tertiary large children hospital in Upper Egypt. This study is a prospective case-control study. All under-five children diagnosed with pneumonia who were admitted to Assiut University Children's Hospital (AUCH) from January 1st to December 31st, 2021, were enrolled. Based on their nutritional assessment, the studied participants were classified into 2 groups: (1): Children with pneumonia and with nutritional deficiency considered as cases, and (2): Children with pneumonia and without nutritional deficiency considered as controls. Three hundred-fifty cases and 154 control subjects were enrolled, respectively. 93.4%, 31.1%, and 61.7% of the cases had underweight, stunting, and wasting, respectively. Among those cases, there were significant differences between survivors and non-survivors with regard to some clinicodemographic factors, laboratory parameters, and anthropometric parameters. Lack of compulsory vaccination, presence of sepsis, and blood transfusion (OR 2.874, 95% CI 0.048 - 2.988, p = 0.004, 2.627, 0.040 - 2.677, p = 0.009, and 4.108, 0.134 - 3.381, p < 0.001, respectively) were significant independent predictors for mortality among malnourished children with pneumonia.    Conclusion: Malnutrition has a high prevalence in under-five children with pneumonia in our locality. It has adverse effects on the outcomes and in-hospital mortality of those children. Lack of compulsory vaccination, presence of sepsis, and blood transfusion were significant independent predictors of mortality in malnourished children with pneumonia. Larger multicenter studies are warranted. What is Known: • Malnutrition has adverse impacts on under-five children with pneumonia. • Malnutrition could be a reason for in-hospital mortality among under-five children with pneumonia. What is New: • Malnutrition has a high prevalence in under-five children with pneumonia in Upper Egypt, with its adverse effects on the outcomes and mortality of those children. • Lack of vaccination, presence of sepsis, and blood transfusion are significant independent predictors of mortality in malnourished children with pneumonia in Upper Egypt.


Subject(s)
Malnutrition , Pneumonia , Sepsis , Humans , Child , Infant , Case-Control Studies , Prevalence , Egypt/epidemiology , Malnutrition/complications , Malnutrition/epidemiology , Pneumonia/complications , Pneumonia/epidemiology
6.
J Exerc Sci Fit ; 21(4): 395-404, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37954548

ABSTRACT

Background/objective: Comparison between different training volumes of high-intensity interval training (HIIT) is understudied in type 2 diabetes. This study aimed to compare the effects of low- and high-volume HIIT on glycemic control, blood lipids, blood pressure, anthropometric adiposity measures, cardiorespiratory fitness, and health-related quality of life (HRQoL) in women with type 2 diabetes. Methods: Seventy-two obese women with type 2 diabetes aged 36-55 were randomly assigned to a low-volume HIIT group (i.e., 2 × 4-min high-intensity treadmill exercise at 85%-90% of peak heart rate, with a 3-min active recovery interval in between), a high-volume HIIT group (i.e., 4 × 4-min high-intensity treadmill exercise at 85%-90% of peak heart rate, with three 3-min active recovery intervals in between), and a non-exercising control group. Patients in HIIT groups exercised three days a week for 12 weeks. All patients received oral hypoglycemic medications with no calorie restrictions. The outcome measures were glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), 2-hour postprandial blood glucose (2-hr PPBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio, time to maximal exhaustion determined from a maximal treadmill exercise test (i.e., a measure of cardiorespiratory fitness), and HRQoL assessed by the 12-item Short Form (SF-12) Health Survey. Results: The low- and high-volume HIIT groups showed significant improvements in all outcome measures compared to the baseline and the non-exercising group (P < 0.05), except for DBP in the low-volume HIIT group (p > 0.05). Also, both low- and high-volume HIIT groups showed similar improvements in TC, HDL, SBP, DBP, BMI, WC, waist-to-hip ratio, and the SF-12 scores, with no significant between-groups difference (p > 0.05). The high-volume HIIT group, however, showed more significant improvements in HbA1c, FBG, 2-hr PPBG, TG, LDL, and treadmill time to maximal exhaustion than the low-volume HIIT group (p < 0.05). The non-exercising group showed non-significant changes in all outcome measures (p > 0.05). Conclusion: Low-volume HIIT could be equally effective as high-volume HIIT for improving TC, HDL, blood pressure, anthropometric adiposity measures, and HRQoL in obese women with type 2 diabetes. Nevertheless, high-volume HIIT could have a greater impact on glycemic control, TG, LDL, and cardiorespiratory fitness in these patients. Trial registration: ClinicalTrials.gov, NCT05110404.

7.
Pediatr Res ; 92(6): 1606-1612, 2022 12.
Article in English | MEDLINE | ID: mdl-35688962

ABSTRACT

BACKGROUND: Epilepsy is a neurological disease that requires long-term antiepileptic drugs (AEDs). The old generation of AEDs may affect serum homocysteine and asymmetric dimethylarginine (ADMA) and disturb lipid levels. The aim of the study was to evaluate serum ADMA, homocysteine, lipid profile, and carotid intima-media thickness (CIMT) in epileptic children. METHODS: This study was implemented on 159 epileptic children who were subdivided into 3 subgroups, with 53 receiving sodium valproate, 53 receiving levetiracetam, and 53 receiving polytherapy, for over 6 months and 53 healthy children. RESULTS: Low-density lipoprotein, triglycerides, and cholesterol levels were increased in epileptic children (p < 0.001), which were higher in those receiving multidrug followed by a valproate receiver. While high-density lipoprotein was lower in those receiving multidrug more than those receiving valproate. ADMA and homocysteine levels increased in epileptic patients than in controls (p < 0.001). Higher ADMA was also observed in the multidrug receiver (5.78 ± 0.62), followed by the levetiracetam group (5.56 ± 0.61). Homocysteine levels were significantly higher in multidrug and valproate-treated children than those treated with levetiracetam. CIMT was significantly higher in multidrug and valproate-treated patients (p < 0.001). CONCLUSIONS: Long-term use of AEDs, especially old-generation polytherapy, can elevate lipid profiles, homocysteine, ADMA levels, and carotid intima-media thickness compared to the minimal effect of new AEDs. IMPACT: The long-term use of antiepileptic drugs, especially old-generation polytherapy, can increase lipid profiles, homocysteine levels, ADMA, and carotid intima thickness compared to the minimal effect of new antiepileptic generation. A routine follow-up of these markers and a lifestyle modification are recommended to avoid cerebrovascular events as much as possible.


Subject(s)
Anticonvulsants , Epilepsy , Humans , Child , Anticonvulsants/adverse effects , Valproic Acid/adverse effects , Levetiracetam/therapeutic use , Carotid Intima-Media Thickness , Epilepsy/drug therapy , Arginine , Homocysteine
8.
Pediatr Res ; 92(6): 1689-1694, 2022 12.
Article in English | MEDLINE | ID: mdl-35338352

ABSTRACT

BACKGROUND: The major increase in the survival rate among children with cancer is due to improvement in the diagnosis and treatment. Despite this increase, childhood cancer survivors (CCS) are at high risk of developing late complications such as nephrotoxicity due to chemotherapy. So, we aimed to detect early subclinical kidney dysfunction among CCS. METHODS: This cross-sectional study was implemented on 52 survivors of childhood cancer recruited from Pediatric Oncology Unit, Menoufia University. Laboratory evaluations for each participant, including complete blood count, serum urea, creatinine, urinary protein, urinary calcium, uric acid, and serum cystatin C and urinary Neutrophil Gelatinase Associated Lipocalin (UrNGAL) by ELISA were obtained. RESULTS: Estimated GFR was decreased in 23.1% of cases, with elevated serum cystatin C, UrNGAL and UrNGAL/Cr. There was a significant increase of Uprotein/Cr, UCa/Cr, UACR (p = 0.02), UrNGAL and UrNGAL/Cr (P < 0.001) in patients with tubular dysfunction compared without tubular dysfunction. There was a significant difference between two groups regarding cisplatin (P = 0.03) and high-dose methotrexate chemotherapy (p = 0.04). The AUCs for detecting kidney tubular dysfunction by UrNGAL and UrNGAL/Cr were 0.807 and 0.747. CONCLUSION: A significant tubular dysfunction among childhood cancer survivors receiving chemotherapy as cisplatin and high-dose methotrexate. IMPACT: Detection of kidney dysfunction mainly tubular in childhood cancer survivors after finishing chemotherapy. Urinary NGAL is a good predictor for detection of tubular dysfunction in childhood cancer survivors after finishing chemotherapy.


Subject(s)
Acute Kidney Injury , Cancer Survivors , Neoplasms , Renal Insufficiency , Humans , Child , Cisplatin , Cystatin C , Methotrexate , Cross-Sectional Studies , Neoplasms/complications , Neoplasms/drug therapy , Lipocalin-2/urine , Kidney , Biomarkers , Acute Kidney Injury/diagnosis , Creatinine
9.
Pediatr Res ; 91(3): 665-671, 2022 02.
Article in English | MEDLINE | ID: mdl-33790414

ABSTRACT

BACKGROUND: Surfactant protein D (SP-D) is a promising biomarker proposed for the prediction of community-acquired pneumonia (CAP) severity. Therefore, we aimed to assess the role of SP-D in the prediction of CAP severity in pediatric patients. METHODS: A prospective cohort study was carried out at the Pediatric Intensive Care Unit (PICU) and wards of Menoufia University Hospital. We recruited 112 children admitted into wards with pneumonia (simple pneumonia) and 68 children admitted into PICU with severe pneumonia (PICU admitted). World Health Organization (WHO) classification and mortality predictive scores were calculated to determine the severity of pneumonia for the two groups, including the Pediatric Respiratory Severity Score (PRESS) and the Predisposition, Insult, Response, and Organ dysfunction modified Score (PIROm). SP-D was measured at admission. RESULTS: The SP-D level was significantly lower in patients with simple pneumonia than in patients with severe pneumonia (P < 0.001). SP-D was significantly higher among children with severe pneumonia, as determined by WHO, PRESS, and PIROm (P = 0.001). SP-D was significantly higher among children with mechanical ventilation, shock, hypoxia, sepsis, and mortality. Receiver operating characteristic curve analysis for SP-D showed that the area under the curve was 0.741 (P value < 0.001), with a sensitivity of 85.3% and a specificity of 44.6%. CONCLUSIONS: Serum SP-D level has a predictive value for the detection of community-acquired pneumonia severity in children. IMPACT: SP-D is a good predictor for the detection of CAP severity in hospitalized children. SP-D was correlated with severity scores and was associated with indicators of CAP severity, including mechanical ventilation, shock, hypoxia, sepsis, and mortality.


Subject(s)
Community-Acquired Infections , Pneumonia , Sepsis , Child , Community-Acquired Infections/diagnosis , Humans , Hypoxia , Pneumonia/diagnosis , Prospective Studies , Pulmonary Surfactant-Associated Protein D , Severity of Illness Index
10.
Angew Chem Int Ed Engl ; 61(11): e202115342, 2022 03 07.
Article in English | MEDLINE | ID: mdl-34935243

ABSTRACT

Streptococcus pyogenes is a primary infective agent that causes approximately 700 million human infections each year, resulting in more than 500 000 deaths. Carbohydrate-based vaccines are proven to be one of the most promising subunit vaccine candidates, as the bacterial glycan pattern(s) are different from mammalian cells and show increased pathogen serotype conservancy than the protein components. In this Review we highlight reverse vaccinology for use in the development of subunit vaccines against S. pyogenes, and report reproducible methods of carbohydrate antigen production, in addition to the structure-immunogenicity correlation between group A carbohydrate epitopes and alternative vaccine antigen carrier systems. We also report recent advances used to overcome hurdles in carbohydrate-based vaccine development.


Subject(s)
Bacterial Vaccines/immunology , Polysaccharides, Bacterial/immunology , Streptococcus pyogenes/immunology , Antibodies, Bacterial/immunology , Bacterial Vaccines/chemical synthesis , Bacterial Vaccines/chemistry , Polysaccharides, Bacterial/chemical synthesis , Polysaccharides, Bacterial/chemistry
11.
BMC Pediatr ; 21(1): 144, 2021 03 25.
Article in English | MEDLINE | ID: mdl-33765980

ABSTRACT

BACKGROUND: Emergence of 2019-nCoV attracted global attention and WHO declared COVID-19 a public health emergency of international concern. Therefore we aimed to explore the severity and atypical manifestations of COVID-19 among children. METHODS: This is an observational cohort study conducted on 398 children with confirmed COVID-19 by using real-time reverse transcriptase polymerase chain reaction assay for detection of 2019-nCoV nucleic acid during the period from March to November 2020. Patients were subdivided regarding the severity of COVID-19 presentation into Group I (Non-severe COVID-19) was admitted into wards and Group II (Severe COVID-19) admitted into the PICU. RESULTS: Non- severe cases were 295cases (74.1%) and 103cases (25.9%) of severe cases. There was a significant difference between age groups of the affected children (P < 0.001) with a median (0-15 years). Boys (52%) are more affected than girls (48%) with significant differences (P < 0.001). 68.6%of confirmed cases had contact history to family members infected with COVID-19. 41.7% of severe patients needed mechanical ventilation. Death of 20.4% of severe cases. In COVID-19 patients, fever, headache, fatigue and shock were the most prominent presentations (95, 60.3, 57.8, and 21.8% respectively). 3.5% of children were manifested with atypical presentations; 1.25% manifested by pictures of acute pancreatitis, 1.25% presented by manifestations of deep venous thrombosis and 1.0% had multisystem inflammatory syndrome (MIS-C). Multivariate regression analysis showed that COVID-19 severity in children was significantly higher among children with higher levels of D-dimer, hypoxia, shock and mechanical ventilation. CONCLUSION: Most children had a non-severe type of COVID-19 and children with severe type had higher levels of D-dimer, hypoxia, shock and mechanical ventilation.


Subject(s)
COVID-19/complications , Pancreatitis/complications , Pediatrics , Systemic Inflammatory Response Syndrome/complications , Acute Disease , Adolescent , COVID-19/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Pancreatitis/diagnosis , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis
12.
Biomarkers ; 24(5): 469-477, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31018714

ABSTRACT

Introduction: Smoking contributes to the death of a million people worldwide each year. Smokers experience an alteration in tumour necrosis factor-alpha (TNF-α), and the risk of expected lung cancer. The study aimed at investigating the expression levels of mir-126 and mir-124, as well as TNF-α as possible biomarkers of expected smoking-related diseases. Methods: Twenty-five male smokers' age and sex-matched with 25 non-smokers were recruited for the present study. Plasma expression levels of mir-126 and mir-124 were evaluated using quantitative real-time PCR. Lipid profile, TNF-α, interleukin-6 and C-reactive protein were assessed in plasma of each participant. Results: Plasma miR-126 was statistically down-regulated in smokers relative to non-smokers; however, mir-124 did not show any significant changes between groups. Among the measured parameters, mir-126 and tumour necrosis factor alpha (TNF-α) displayed a good discrimination and sensitivity between smokers and non-smokers (AUC = 0.809 (95% CI: 0.668-0.95; p < 0.001) and 0.742(95% CI: 0.584-0.9; p < 0.01), respectively. Also, the combined evaluation of miR-126 and TNF-α levels showed high discrimination (AUC= 0.889 (95% CI: 0.779-1.00; p < 0.0001), sensitivity = 85%, and specificity = 80% in the diagnosis of smokers with non-smokers. Conclusions: MiR-126 and TNF-α are potential biomarkers of smoking-related diseases and are important in assessing the expected tobacco-related harm.


Subject(s)
Biomarkers/blood , MicroRNAs/blood , Smokers , Tumor Necrosis Factor-alpha/blood , C-Reactive Protein , Healthy Volunteers , Humans , Interleukin-6/blood , Lung Neoplasms/etiology , Lung Neoplasms/prevention & control , Male , Risk Factors
13.
Pediatr Res ; 93(7): 1794, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36879080
14.
Ultrastruct Pathol ; 42(4): 333-343, 2018.
Article in English | MEDLINE | ID: mdl-29932802

ABSTRACT

Dehydroepiandrosterone (DHEA) is a widespread nutritional "anti-aging" supplement. Exogenous supplementation of DHEA is now being commonly used to augment ovarian stimulation in perimenopausal women with diminished ovarian reserve. Whether DHEA causes side effects in such age is, however, unknown. Thus, this study investigates the effects of pharmacological doses of DHEA supplementation on the liver of perimenopausal rats. DHEA supplementation to perimenopausal rats resulted in slight hepatomegaly and steatosis, hepatocytic hypertrophy, mitochondrial swelling, elevation in serum alanine aminotransaminase levels, in addition to the accumulation of lipid droplets and lipolysosomes in a dose-dependent manner. In conclusion, long-term administration of high doses of DHEA causes ultrastructural alterations and changes in the levels of cholesterol and triglyceride in hepatocytes of perimenopausal rats. DHEA at a dose of 50 mg/kg improves health and decreases the body weight, with the least side effects on the liver of perimenopausal rats.


Subject(s)
Dehydroepiandrosterone/pharmacology , Endoplasmic Reticulum/ultrastructure , Liver/drug effects , Liver/pathology , Perimenopause/drug effects , Animals , Body Weight/drug effects , Cholesterol/metabolism , Liver/ultrastructure , Perimenopause/metabolism , Rats
15.
Pediatr Res ; 92(6): 1504, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36195628
16.
Chin J Cancer ; 33(7): 356-64, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24636230

ABSTRACT

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.


Subject(s)
Acetaminophen/therapeutic use , Disease Progression , Lung Neoplasms/secondary , Melanoma/drug therapy , Pleural Neoplasms/secondary , Prognosis , Pyruvates/therapeutic use , Treatment Outcome , Adult , Carcinoma, Hepatocellular , Drug Therapy, Combination , Enzyme Inhibitors , Glutathione , Glycolysis , Hexokinase , Humans , L-Lactate Dehydrogenase , Lactic Acid , Male , Necrosis , Neovascularization, Pathologic , Pyruvates/adverse effects
17.
Eur J Gastroenterol Hepatol ; 36(8): 1022-1028, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38973543

ABSTRACT

BACKGROUND: Vasodilatation and bacterial dislocation are the main contributors to the catastrophic events in patients with decompensated liver cirrhosis (DLC). AIM: The aim of this study was to evaluate the impacts of adding midodrine and rifaximin on morbidity, mortality, and quality of life in patients with DLC. METHODS: This interventional clinical study included 100 consecutively enrolled DLC patients randomized 1 : 1 into two groups. Group A received oral midodrine (5 mg/8 h) and rifaximin (550 mg/12 h) with standard diuretic therapy, while group B received only standard diuretic therapy. Clinical and laboratory data, including the McGill Quality of Life Questionnaire, were evaluated over a 3-month treatment period. RESULTS: In the study group, there was a significant reduction in Child-Pugh and Model for End-Stage Liver Disease scores, international normalized ratio, and mean arterial blood pressure at 2, 6, and 12 weeks (P < 0.05). Ascites, spontaneous bacterial peritonitis incidence, hematemesis, paracentesis need, and hepatic encephalopathy showed improvement after 12 weeks compared with the control group. McGill Quality of Life Questionnaire significantly improved after 6 and 12 weeks (P < 0.05). Survival rates demonstrated a noteworthy improvement (P = 0.014), substantiated by evidence in both univariate and multivariate regression analyses. CONCLUSION: Combined midodrine with rifaximin represents an endowment to patients with DLC with spectacular improvements in synthetic liver functions, along with improved quality of life, and survival.


Subject(s)
Liver Cirrhosis , Midodrine , Quality of Life , Rifamycins , Rifaximin , Humans , Rifaximin/therapeutic use , Female , Midodrine/therapeutic use , Midodrine/adverse effects , Male , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Liver Cirrhosis/drug therapy , Middle Aged , Rifamycins/therapeutic use , Rifamycins/adverse effects , Treatment Outcome , Drug Therapy, Combination , Adult , Ascites/etiology , Ascites/drug therapy , Ascites/mortality , Hepatic Encephalopathy/drug therapy , Hepatic Encephalopathy/etiology , Aged , Surveys and Questionnaires , Peritonitis/mortality , Time Factors
18.
Vet Immunol Immunopathol ; 270: 110730, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38422854

ABSTRACT

Details on the origin and function of the immune system are beginning to emerge from genomic studies tracing the origin of B and T cells and the major histocompatibility complex. This is being accomplished through identification of DNA sequences of ancestral genes present in the genomes of lineages of vertebrates that have evolved from a common primordial ancestor. Information on the evolution of the composition and function of the immune system is being obtained through development of monoclonal antibodies (mAbs) specific for the MHC class I and II molecules and differentially expressed on leukocytes differentiation molecules (LDM). The mAbs have provided the tools needed to compare the similarities and differences in the phenotype and function of immune systems that have evolved during speciation. The majority of information currently available on evolution of the composition and function of the immune system is derived from study of the immune systems in humans and mice. As described in the present review, further information is beginning to emerge from comparative studies of the immune systems in the extant lineages of species present in the two orders of ungulates, Perissodactyla and Artiodactyla. Methods have been developed to facilitate comparative research across species on pathogens affecting animal and human health.


Subject(s)
Antibodies, Monoclonal , Mammals , Humans , Animals , Mice , Antibodies, Monoclonal/genetics , Major Histocompatibility Complex , Genes, MHC Class I , T-Lymphocytes
19.
J Surg Case Rep ; 2024(2): rjae052, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38357384

ABSTRACT

Motor vehicle accidents are a significant cause of morbidity and mortality worldwide. Airbags aim to reduce the severity of motor vehicle accidents, but their deployment is not without risks. This study presents five cases presenting with diverse forms of upper extremity injuries following airbag deployment. The presented cases highlight the variety of clinical presentations, the differences in diagnostics in terms of imaging modalities, as well as the spectrum of possible outcomes from complete healing to decreased range of motion to persistent neurological symptoms. Understanding the mechanisms and presentations of such injuries can only help in improving and creating new strategies for the prevention of such injuries, as well as their management.

20.
Diseases ; 12(3)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38534974

ABSTRACT

Post-marketing hepatotoxicity findings are more common or occur much later. NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen are consumed in large quantities around the world. NSAIDs have a low incidence of hepatotoxicity but their wide use makes them a major contributor to drug-induced liver injury. Hepatitis is linked to systemic oxidative stress which results in cellular necrosis and fibrosis, as well as tissue lipoprotein peroxidation and glutathione depletion. Given the lack of safe and effective anti-hepatitis drugs in medicine today, natural substances appear to be a promising and safe alternative. Propolis and chitosan are considered natural substances that have a protective effect on the hepatocytes. The purpose of this study was to validate the protective effect of propolis/chitosan nanoparticle extracts on ibuprofen-induced hepatotoxicity. Thirty (30) albino rats were used for the experiment. Animals were exposed to ibuprofen (400 mg/kg body weight/day) for 4 weeks (7 days/week) followed by treatment with propolis (200 mg/kg body weight/day) and chitosan extract (200 mg/kg body weight/day) separately and also in combination for consecutive 4 weeks. This study revealed a significant increase in serum transaminases, alkaline phosphatase, albumin, and total bilirubin in serum, as well as an increase in lipid peroxidation (MDA) and nitric oxide (NO). Furthermore, GSH, GST, and SOD decreased significantly in the group that was exposed to ibuprofen. Furthermore, there was a significant increase in pro-inflammatory parameters such as IL-1ß and NF-ĸB, as well as low levels of anti-inflammatory parameters such as IL-6 and BCl-2. These alterations were improved by propolis and chitosan extracts, which was further confirmed in experimental animals. This study demonstrated that propolis and chitosan nanoparticle extracts have the potential to protect against hepatotoxicity induced by ibuprofen, due to their ability to regulate anti-inflammatory and anti-oxidative defense activities.

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