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Original Article Open Access
Impact of Intermediate-term Oral Contraceptive Use on Oxidative Stress, Lipid Profile, and Liver Function in Iraqi Women: A Comprehensive Biochemical Assessment
Hayder Hatem Sultan, Amir Teimourpour, Ziba Majidi, Fariba Nabatchian
Published online January 25, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00035
Abstract
Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study [...] Read more.

Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study aimed to evaluate the impact of intermediate-term OCP use (Yasmin) on oxidative stress, lipid profile, and liver function, with particular emphasis on antioxidant markers, lipid metabolism, and hepatic enzyme activity, to better understand the potential metabolic and hepatic effects.

A case-control study was conducted in Maysan Governorate, Iraq, involving 150 women (100 OCP users and 50 non-users). Blood samples were collected from Al-Sadr Teaching Hospital and a specialized clinic between February and April 2023. Serum levels of antioxidants, lipids, and liver enzymes were measured using biochemical assays.

OCP users had significantly lower levels of glutathione peroxidase vitamin E and uric acid (p < 0.001) compared to non-users. Lipid profiles showed that OCP users had higher levels of triglyceride and low-density lipoprotein (p < 0.05), whereas total cholesterol was significantly higher in non-users (p < 0.05). Liver enzyme activity, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total serum bilirubin, did not show statistically significant differences (p > 0.05). Longer duration of OCP use was significantly negatively correlated with vitamin E levels (r = −0.67), glutathione peroxidase activity (r = −0.56), uric acid levels (r = −0.45) and high-density lipoprotein (r = −0.54). Positive correlations were found between the duration of OCP use and total cholesterol (r = 0.62), triglyceride (r = 0.58), low-density lipoprotein (r = 0.60), and liver enzymes alanine aminotransferase (r = 0.66) and aspartate aminotransferase (r = 0.64).

Intermediate-term OCP use was associated with changes in oxidative stress and lipid metabolism, potentially increasing cardiovascular and metabolic risks. Regular monitoring of these parameters is recommended for OCP users.

Full article
Case Series Open Access
Disseminated Carcinomatosis of Bone Marrow with or without an Unknown Primary Site: A Case Series
Kenji Miki, Masayoshi Yamanishi, Satoko Mibayashi, Shinsaku Imashuku
Published online May 14, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00064
Abstract
Disseminated carcinomatosis of bone marrow (DCBM) occurs mostly in stomach cancer patients; however, characterizing tumor cells morphologically and phenotypically in the bone marrow [...] Read more.

Disseminated carcinomatosis of bone marrow (DCBM) occurs mostly in stomach cancer patients; however, characterizing tumor cells morphologically and phenotypically in the bone marrow is not an easy task. In addition, among patients with DCBM, an unknown primary site (CUPS) is rarely noted despite standard clinical evaluation, imaging studies, and endoscopic findings. This study aimed to clarify the diagnosis/outcome of DCBM in elderly patients we have treated.

Here, we report eight DCBM cases. Once tumor clumps were noted in the bone marrow, we performed serum tumor markers, immunostaining of tumor cells in the bone marrow clot, or biopsy preparations. In addition, imaging studies (CT/MRI/ FDG PET-CT) were performed.

Of eight cases, two were diagnosed with DCBM/CUPS. Among the eight cases, six fatal cases had a median survival time of 2 months (ranging from <0.5 to 8 months) from DCBM detection to death or the time of this writing, while the CUPS cases were still alive at 2+ and 3+ months, respectively. The outcomes of DCBM and DCBM/CUPS, particularly in elderly patients, were dismal, and comprehensive genomic profiling could not be perform in these cases.

The use of conventional morphological/phenotypical characteristics to improve the prognosis of DCBM patients is limited. Consequently, the application of comprehensive genomic profiling is recommended to enhance diagnostic and therapeutic approaches.

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Short Communication Open Access
The Pharmacokinetics of Butylscopolamine in Camel Plasma after Intravenous Administration
Majed Saeed Nassar, Sayed Wajid, Nawal Alkatheeri, Ibrahim A. Wasfi
Published online August 20, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00013S
Abstract
Camels are commonly administered butylscopolamine (BSA), an antimuscarinic quaternary ammonium derivative, to reduce spasms in the smooth muscles of their urinary and gastrointestinal [...] Read more.

Camels are commonly administered butylscopolamine (BSA), an antimuscarinic quaternary ammonium derivative, to reduce spasms in the smooth muscles of their urinary and gastrointestinal tracts. However, its presence in body fluids after racing is prohibited by animal racing authorities. The current study aimed to conduct a pilot pharmacokinetic study of BSA in healthy camels. The goal was to obtain initial pharmacokinetic parameters and use these parameters to predict plasma concentrations from the dose and clearance. This will help advise on a withdrawal time for BSA administration before camel racing. The pharmacokinetics of BSA were evaluated in three healthy camels after a single intravenous dose of 0.2 mg/kg body weight. Sensitive liquid chromatography with tandem mass spectrometry was used for the quantification of BSA and the internal standard, ipratropium, in plasma. BSA concentration versus time data were best described by a two-compartment open model. The pharmacokinetic parameters (median and range) were as follows: terminal elimination half-life was 2.29 (1.48–2.46) h, plasma clearance was 1,018.5 (772.4–1,024.0) mL/h/kg, volume of distribution at steady state was 931.9 (700.0–1,068.7) mL/kg, Cmax was 443.9 (351.1–443.9) ng/mL, and Tmax was 0.5 (0.25–0.75) h. BSA’s irrelevant plasma concentration was estimated to be 20 ng/mL. Consequently, it can be concluded that plasma would not contain BSA at the screening level of 20 ng/mL at the usual dose of 0.2 mg/kg body weight 24 h before camel racing.

Full article
Letter to the Editor Open Access
Impact of Proteinuria on Liver Enzyme Levels
David Yardeni, Asif Hitawala, Lilian Howard, Theo Heller, Meryl Waldman
Published online July 19, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00169
Original Article Open Access
The Aquaporin-4 Inhibitor, N-(1,3,4-thiadiazol-2-yl)-3-pyridinecarboxamide, Inhibits the Glymphatic System: A Laboratory Study
Chuang Lian, Te Zhang, Peng Cheng, Longyun Li, Guoqing Zhao, Xuli Ren
Published online November 15, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00029
Abstract
Aquaporin-4 (AQP4) plays a crucial role in the glymphatic system and is vital for maintaining homeostasis in the central nervous system. This study aimed to investigate the effects [...] Read more.

Aquaporin-4 (AQP4) plays a crucial role in the glymphatic system and is vital for maintaining homeostasis in the central nervous system. This study aimed to investigate the effects of N-(1,3,4-thiadiazol-2-yl)-3-pyridinecarboxamide (TGN-020), a selective AQP4 inhibitor, on glymphatic function and to assess its impact on short-term behavior in mice.

In this laboratory study, mice were randomly assigned to TGN-020-treated and control groups. We evaluated glymphatic function by measuring the distribution of Evans blue dye in the brain following injection into the cisterna magna. Behavioral assessment of cognitive function was performed using open field and Morris water maze tests. AQP4 protein expression levels were analyzed via immunohistochemistry. Statistical comparisons were conducted using the one-way analysis of variance to evaluate the results among groups.

Our findings revealed that the areas of Evans blue dye in the dorsal (p < 0.001) and ventral (p < 0.001) surfaces of the brain were significantly reduced in the TGN-020 group compared to the control group, indicating impaired glymphatic function. However, behavioral tests demonstrated no significant short-term changes; the mean distance traveled in the open field was 4,345 cm in the control group and 4,049 cm in the TGN-020 group (p = 0.5625), while the mean speed was 2.649 cm/s for controls and 2.868 cm/s for the TGN-020 group (p = 0.6762). In the Morris water maze, latency was comparable (36.33 s for TGN-020 vs. 34.89 s for controls, p = 0.758). Additionally, no significant differences in AQP4 expression intensity were observed between the two groups.

Our study demonstrates that acute inhibition of AQP4 through a single dose of TGN-020 significantly impairs glymphatic function without inducing short-term behavioral abnormalities in mice. These findings contribute to understanding AQP4’s role in the glymphatic system and its potential implications for neurological function.

Full article
Case Report Open Access
Breast Cancer Metastasizing to the Lower Gastrointestinal Tract (the Small Bowel and Colon): A Case Presentation and Comprehensive Review of the Literature
Teresa Da Cunha, Simon Abi Saleh, Murali Dharan
Published online June 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00001
Abstract
Breast cancer metastases to the lower gastrointestinal tract (small bowel and colon) are rare, but there is a growing number of case reports in the literature. The overall incidence [...] Read more.

Breast cancer metastases to the lower gastrointestinal tract (small bowel and colon) are rare, but there is a growing number of case reports in the literature. The overall incidence of this condition is not well established, and there might be underdiagnosis. The clinical presentation and endoscopic findings are often nonspecific and variable, potentially leading to misdiagnosis or underdiagnosis. Moreover, there are currently no guidelines for gastrointestinal surveillance of these patients. Given the potential diagnostic challenges, a high level of clinical suspicion is necessary. We present a clinical case to highlight subtle endoscopic findings of breast cancer metastasis to the colon, followed by a review summarizing the available literature on breast cancer metastases to the duodenum, jejunum, ileum, colon, rectum, and anus focusing on the clinical presentation, endoscopic features, imaging modalities, treatment, and outcome.

Full article
Review Article Open Access
Mutation Detection of Phosphatidylinositol-4,5-bisphosphate 3-Kinase Catalytic Subunit Alpha for Treatment Guidance in Breast Cancer
Willy Sandhika, Lina Patricia Gutjahr, Lusiani Tjandra
Published online June 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00013
Abstract
Molecular analysis of breast cancer tissue has revealed that breast cancer is not a uniform disease. Each breast cancer patient has several molecular signatures that differ from [...] Read more.

Molecular analysis of breast cancer tissue has revealed that breast cancer is not a uniform disease. Each breast cancer patient has several molecular signatures that differ from those of others. Therefore, breast cancer therapy should be personalized, depending on its molecular signatures. Breast cancer with hormonal receptors can be treated with a selective estrogen receptor modulator or selective estrogen receptor degrader therapy, while breast cancer with overexpression of human epidermal growth factor receptor 2 (HER2)-neu gene responds excellently to anti-HER2-neu therapy. For patients with advanced breast cancer that already has distant metastasis and a poor prognosis, a new agent has been discovered. The phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) inhibitor has been proven effective in treating advanced breast cancer with a PIK3CA gene mutation. This therapy can be administered to HER2-negative breast cancer patients and in combination with selective estrogen receptor degrader therapy for post-menopausal patients with positive hormonal receptors. Although this treatment is effective, it cannot be given to every advanced breast cancer patient. Before administering the treatment, a PIK3CA mutation test is compulsory. PIK3CA mutation detection in breast cancer can predict the cancer’s response to the PIK3CA inhibitor, providing information on which patients will benefit from the treatment.

Full article
Original Article Open Access
Prevalence of Hepatitis D Virus Antibody Positivity in Chinese Patients with Chronic Hepatitis B Virus Infection
Xieer Liang, Qiaoqiao Chen, Hong Tang, Yujuan Guan, Minfeng Liang, Peng Hu, Wen Xie, Huiying Rao, Junqi Niu, Liang Chen, Li Yan, Xiaowei Chen, Xiaohe Li, Yulin Zhao, Oliver Lenz, Michael Biermer, Jinlin Hou
Published online February 24, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00313
Abstract
Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate [...] Read more.

Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate the current epidemiology of HDV.

Patients with chronic HBV infection, with documented serum hepatitis B surface antigen (HBsAg) positivity for more than six months, were enrolled across China. Blood samples were collected at baseline for central evaluations of HDV antibody and HBsAg quantification. Assessments for antibodies of hepatitis A virus, hepatitis C virus, hepatitis E virus, and human immunodeficiency virus, as well as HDV RNA quantification, were performed in patients who tested positive for HDV antibodies.

Of the 5,044 enrolled patients between September 24, 2021, and December 28, 2022, 4,936 patients were included in the analysis. The mean age (±standard deviation) was 42.9 ± 9.9 years, and 69.8% of patients were male. The mean alanine aminotransferase level was 34 ± 58 U/L, and 1,509 (30.6%) patients were hepatitis B e antigen-positive. The mean (standard deviation) HBsAg level at baseline was 3,535 ± 11,292 IU/mL among 4,842 patients who were HBsAg positive. The rate of HBV infection and HDV antibody positivity was 0.24% (95% confidence interval: 0.1–0.4%), and only one patient was HDV RNA positive.

The prevalence of HDV antibody positivity was 0.24% in Chinese patients with chronic HBV infection, and only one patient with both anti-HDV antibody and HDV RNA positivity was observed in this study.

Full article
Review Article Open Access
Antioxidant-enzyme Interaction in Non-communicable Diseases
Benjamin O. Ezema, Chijioke Nwoye Eze, Thecla Okeahunwa Ayoka, Charles Okeke Nnadi
Published online December 25, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00020
Abstract
Free radicals are produced in the body during normal cellular metabolic activities, and their excessive accumulation can overwhelm the natural antioxidant mechanisms. This leads [...] Read more.

Free radicals are produced in the body during normal cellular metabolic activities, and their excessive accumulation can overwhelm the natural antioxidant mechanisms. This leads to oxidative stress, which is associated with the development and progression of non-communicable diseases (NCDs) such as liver and kidney diseases, cardiovascular diseases, neurodegenerative diseases, cancer, and diabetes. Enzymes play a significant role in maintaining a balance between antioxidants and free radicals by either enhancing the production of antioxidants or slowing down the generation of free radicals in the body. There is no up-to-date review on how antioxidant-enzyme interactions modulate the development and progression of NCDs. This review, therefore, discusses the mechanisms of antioxidant-enzyme interactions in the control of oxidative stress, as well as the implications and prospects of these interactions in the management of NCDs. Therapeutic strategies targeting antioxidant-enzyme interactions in the natural defense mechanisms of the body against oxidative stress can provide targeted benefits in the management of various NCDs. The mechanisms of interaction of some antioxidants with catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione S-transferases, thioredoxin protein, and thioredoxin reductase suggest their strong involvement in mitigating the development and progression of NCDs. Moreover, understanding the specific interactions and signaling pathways involved in antioxidant-enzyme interactions could facilitate the emergence of novel and effective therapeutic strategies for the management of NCDs and should be considered a primary goal of future studies. This study provides the necessary template, encourages discussion, and creates more opportunities for the next stage in the development of antioxidant therapies.

Full article
Original Article Open Access
Relationship between Concentrations of Oxygen and Levels of Oxidative Stress in Patients Receiving Oxygen Therapy for Severe COVID-19 Pneumonia
Salih Özenç, Pınar Yıldız Gülhan, Merve Alpay, Şule Yıldız, Nevra Ezgi Yaşlı, Peri Meram Arbak
Published online November 14, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00015
Abstract
Severe COVID-19 pneumonia often requires high concentrations of oxygen, which can potentially lead to oxidative stress and lung injury. This study aimed to investigate the impact [...] Read more.

Severe COVID-19 pneumonia often requires high concentrations of oxygen, which can potentially lead to oxidative stress and lung injury. This study aimed to investigate the impact of different oxygen therapy modalities on oxidative stress by comparing malondialdehyde (MDA) levels, an oxidative stress marker, and glutathione (GSH), an antioxidant marker, in patients with severe COVID-19 pneumonia.

This study included 50 patients with COVID-19 pneumonia who received oxygen therapy using a reservoir mask at ≥15 L/m, high-flow oxygen therapy at 60 L/m, or oxygen therapy with noninvasive mechanical ventilation at fraction of inspired O2 (FiO2) levels of ≥60%. GSH and MDA levels were measured 48 h after starting oxygen therapy at FiO2 ≥ 60% and 48 h after switching to nasal cannula oxygen therapy at 2–4 L/m.

Overall, 60% (n = 30) of the patients were men, and 40% (n = 20) were women. In patients with accompanying hypertension, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.046). A significant difference in MDA was not found after switching to lower oxygen flow (p = 0.064) in patients with underlying diabetes mellitus. GSH levels in patients with underlying diabetes mellitus were higher during oxygen therapy at FiO2 ≥ 60% and decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.021).

This study compared MDA and GSH levels among patients receiving oxygen therapy at high and low concentrations for severe COVID-19 pneumonia. The results revealed that patients who died of COVID-19 pneumonia had significantly higher mean MDA levels than those who survived. In patients with underlying HT, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased during nasal oxygen therapy at 2–4 L/m; this difference was significant. The increase in serum MDA levels during high-flow oxygen therapy and the decrease during low-flow therapy in patients with COVID-19 pneumonia accompanied by hypertension suggest that oxidative stress due to hyperoxia should be taken into consideration.

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