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Introduction Chronic metabolic disorders such as diabetes mellitus (DM) are becoming a global health concern. According to recent studies, the pathophysiology of DM may involve factors other than traditional glycemic control, such as electrolyte balance and thiamin status. Therefore, this study evaluated the relationship between sodium and potassium and serum thiamin levels in patients with type 1 and type 2 DM. Methods This study was conducted in multiple diabetic outpatient clinics and centers in Karachi, Pakistan, using a non-probability convenience sampling method. The study lasted for approximately six months after the synopsis was approved. A total of 64 patients were selected, 32 of whom each had type 1 and type 2 DM. All patients who were between the ages of 25 and 46 years old and had either type 1 or type 2 DM were included in the study. A Mann-Whitney test and an independent t-test were used to compare the means between the two study groups. Pearson's correlation and chi-square tests were used to determine the variables, correlations, and associations with type 1 and type 2 DM. Results The study findings showed that the distribution of gender among diabetic patients revealed that among males, eight (25.0%) had type 1 DM, and 10 (31.2%) had type 2 DM. Among females, 24 (75.0%) had type 1 DM, and 22 (68.8%) had type 2 DM. Significant correlations were observed in the means of blood glucose levels, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), and serum thiamin levels, among patients with type 1 and type 2 DM (p < 0.001). The HbA1c, FBS, and serum thiamin levels were significantly higher in type 2 DM patients than in type 1 DM patients. Among patients with type 1 DM, sodium levels were not substantially correlated with thiamin levels (p = 0.570, r = 0.104), whereas potassium levels were significantly correlated with thiamin levels (p = 0.005, r = 0.263). Conclusion We conclude that the sodium level was not significantly correlated with serum thiamin status in type 1 and type 2 DM, whereas a low positive correlation was observed between potassium and serum thiamin levels in type 1 DM. However, there was no significant correlation concerning potassium levels in type 2 DM.
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Background Primary hypothyroidism is a common endocrine disorder resulting from inadequate production of thyroid hormones. Anemia is a common condition that can occur in hypothyroidism. Anemia may occur due to nutrient deficiency, such as iron or vitamin B12 deficiency due to chronic disease in hypothyroidism. Therefore, it is important to evaluate the cause of anemia in hypothyroidism. Objective The aim of this study was to determine the frequency of anemia and its types in patients with primary hypothyroidism. Methods This was a prospective cross-sectional observational study conducted at the Department of Medicine, Jinnah Postgraduate Medical Center, Karachi, Pakistan, using non-probability consecutive sampling. A total of 176 adults aged 18-65 years of either gender, newly diagnosed with primary hypothyroidism, or with any of its symptoms were included in the study. Patients already on anti-thyroid medication and with post-thyroidectomy hypothyroidism were excluded from the study. The duration of the study was 1.5 years, from January 2020 to July 2021. After ethical approval, written informed consent was obtained from each patient. Demographical data along with results of complete blood picture, including Hb and MCV for diagnosing anemia and its types were recorded on a pre-designed proforma. The chi-square test was applied keeping p < 0.05 as statistically significant. Results The mean age of the patients was 42.19 ± 8.43 years, with 59.66% (n = 105) females and 40.34% (n = 71) males. A total of 67% (n =118) patients were found to be anemic. Of these, 38.64% (n = 68) patients had normocytic anemia, 19.32% (n = 34) microcytic anemia, and 9.25% (n = 16) patients had macrocytic anemia; 56.34% (n = 40) males and 74.29% (n = 78) females were reported to be anemic (p = 0.01). Conclusion In our study, the frequency of anemia in patients with hypothyroidism was high, with normocytic anemia being the most common type. It is important to know the type of anemia in hypothyroidism, as normocytic anemia is due to the chronic disease process (anemia of chronic disease) and may not respond to nutrient supplementation. Conversely, microcytic anemia is commonly due to iron deficiency and macrocytic anemia is due to vitamin B12 deficiency and therefore, they require replacement therapy. In any case, it is important to identify and treat the underlying cause of anemia.
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Introduction Serum urea and creatinine levels are the most commonly recognized parameters for evaluating renal impairment in patients with diabetes mellitus (DM). Therefore, this study evaluated the correlation between urea and creatinine levels and thiamin levels in patients with type 1 DM (T1DM) and type 2 DM (T2DM). Methods This multi-center, cross-sectional study was conducted at diabetic outpatient clinics in Karachi. The duration of the study was six months, from 1st January 2023 to 30th June 2023. A total of 60 patients were enrolled and divided into two groups, i.e., T1DM and T2DM, each containing 30 patients of both genders between the ages of 24 and 42 years. Demographic data and biochemical variables, such as urea, creatinine, random blood sugar, fasting blood sugar, hemoglobin A1c, and serum thiamin levels, were assessed. The Mann-Whitney U test and independent t-test were used to associate the means between the two study groups. The chi-square test and Spearman's correlation coefficient were used to determine the associations between the variables and T1DM and T2DM. Results The study results revealed that patients with T2DM had a significantly higher frequency of hypertension (p = 0.039), neuropathy (p = 0.038), and coronary artery disease (p = 0.010) than those with T1DM, in both genders. The level of serum thiamin was found to be significantly higher (p < 0.001) in T2DM (14.8 ± 4.82) than in T1DM patients (7.34 ± 1.90). Similarly, serum creatinine was higher in T2DM than in T1DM patients (0.83 ± 0.12 vs. 0.76 ± 0.17, p = 0.025). Moreover, the correlation of urea and creatinine with thiamin levels in T1DM and T2DM patients revealed that in T1DM and T2DM patients, urea and creatinine showed an insignificant positive correlation with thiamin levels. Conclusion We found a significantly higher level of serum creatinine and thiamin levels in T2DM patients than in T1DM; however, there was no significant correlation between urea and creatinine levels and thiamin status in T1DM and T2DM patients. Therefore, we conclude that although serum urea, creatinine, and serum thiamin are important disease biomarkers in diabetic patients, there is no correlation between them.
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Preterm prelabor rupture of the membranes (pPROM) may lead to preterm births (PTBs). We investigated premature senescence of fetal membranes in women with pPROM and spontaneous PTB with intact membranes (<34 weeks) and the inducibility fetal membrane senescence phenotype by oxidative stress in vitro. IHC was performed for p53, p21, and phospho (p)-p38 mitogen-activated protein kinase (MAPK) as markers of senescence phenotype in pPROM, PTBs, and term births. Term fetal membranes were exposed to cigarette smoke extract to induce oxidative stress. Western blots documented p-p53 and p-p38 MAPK. Transmission electron microscopy assessed cellular morphologic features in clinical and cigarette smoke extract-treated membranes. A total of 80% of pPROM cells and >60% of term cells were positive for all three senescence phenotype markers, and concentrations were higher than in PTBs (P < 0.05). p53 staining was comparable in membranes from PTB and term birth pregnancies, whereas only <30% and <45% of cells were positive for p21 and p38 MAPK, respectively. In vitro cigarette smoke extract exposure increased p-p38 MAPK without any detectable change in p-p53 MAPK. Enlargement of organelles consistent with senescence phenotype was evident in pPROM and term membranes in vivo and after cigarette smoke extract treatment in vitro but was less apparent in PTBs. Histologic and biochemical resemblance of pPROM and term membranes suggests premature senescence of the membranes is a mechanistic feature in pPROM, and this can be phenocopied in an in vitro model.
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Membranas Extraembrionárias/metabolismo , Ruptura Prematura de Membranas Fetais/metabolismo , Estresse Oxidativo , Nascimento Prematuro/metabolismo , Biomarcadores/metabolismo , Senescência Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Membranas Extraembrionárias/patologia , Feminino , Ruptura Prematura de Membranas Fetais/patologia , Humanos , Gravidez , Nascimento Prematuro/patologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
PROBLEM: The most common DNA lesion generated by oxidative stress (OS) is 7, 8-dihydro-8-oxoguanine (8-oxoG) whose excision repair is performed by 8-oxoguanine glycosylase (OGG1). We investigated OGG1 expression changes in fetal membranes from spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) and its changes in vitro in normal fetal membranes exposed to OS inducer water-soluble cigarette smoke extract (CSE). METHOD OF STUDY: DNA damage was determined in amnion cells treated with CSE by comet and FLARE assays. OGG1 mRNA expression and localization in fetal membranes from clinical specimens and in normal term membranes exposed to CSE were examined by QRT-PCR and by immunohistochemistry. RESULTS: DNA strand and base damage was seen in amnion cells exposed to CSE. OGG1 expression was 2.5-fold higher in PTB samples compared with pPROM (P = 0.045). No significant difference was seen between term and pPROM or PTB and term. CSE treatment showed a nonsignificant decrease in OGG1. OGG1 was localized to both amnion and chorion with less intense staining in pPROM and CSE-treated membranes. CONCLUSION: Increased OS-induced DNA damage predominated by 8-oxoG is likely to persist in fetal cells due to reduced availability of base excision repair enzyme OGG1. This can likely lead to fetal cell senescence associated with some adverse pregnancy outcome.
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Dano ao DNA/fisiologia , DNA Glicosilases/biossíntese , Membranas Extraembrionárias/enzimologia , Oxidantes/toxicidade , Adulto , Células Cultivadas , Ensaio Cometa , Feminino , Ruptura Prematura de Membranas Fetais/enzimologia , Feto , Humanos , Imuno-Histoquímica , Estresse Oxidativo/fisiologia , Gravidez , Nascimento Prematuro/enzimologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fumaça/efeitos adversos , Nicotiana/toxicidadeRESUMO
Spontaneous preterm birth (PTB, <37 weeks gestation) is a major public health concern, and children born preterm have a higher risk of morbidity and mortality throughout their lives. Recent studies suggest that fetal DNA methylation of several genes varies across a range of gestational ages (GA), but it is not yet clear if fetal epigenetic changes associate with PTB. The objective of this study is to interrogate methylation patterns across the genome in fetal leukocyte DNA from African Americans with early PTB (24(1/7)-34(0/7) weeks; Nâ=â22) or term births (39(0/7)-40(6/7)weeks; Nâ=â28) and to evaluate the association of each CpG site with PTB and GA. DNA methylation was assessed across the genome with the HumanMethylation450 BeadChip. For each individual sample and CpG site, the proportion of DNA methylation was estimated. The associations between methylation and PTB or GA were evaluated by fitting a separate linear model for each CpG site, adjusting for relevant covariates. Overall, 29 CpG sites associated with PTB (FDR<.05; 5.7×10(-10)
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Metilação de DNA , Feto/metabolismo , Idade Gestacional , Nascimento Prematuro/genética , Estudos de Coortes , Ilhas de CpG , Epigênese Genética , Feminino , Humanos , Recém-Nascido , Masculino , GravidezRESUMO
OBJECTIVE: Oxidative stress is a postulated etiology of spontaneous preterm birth (PTB) and preterm prelabor rupture of the membranes (pPROM); however, the precise mechanistic role of reactive oxygen species (ROS) in these complications is unclear. The objective of this study is to examine impact of a water soluble cigarette smoke extract (wsCSE), a predicted cause of pregnancy complications, on human amnion epithelial cells. METHODS: Amnion cells isolated from fetal membranes were exposed to wsCSE prepared in cell culture medium and changes in ROS levels, DNA base and strand damage was determined by using 2'7'-dichlorodihydro-fluorescein and comet assays as well as Fragment Length Analysis using Repair Enzymes (FLARE) assays, respectively. Western blot analyses were used to determine the changes in mass and post-translational modification of apoptosis signal-regulating kinase (ASK1), phospho-p38 (P-p38 MAPK), and p19(arf). Expression of senescence-associated ß-galectosidase (SAß-gal) was used to confirm cell ageing in situ. RESULTS: ROS levels in wsCSE-exposed amnion cells increased rapidly (within 2 min) and significantly (p<0.01) at all-time points, and DNA strand and base damage was evidenced by comet and FLARE assays. Activation of ASK1, P-p38 MAPK and p19(Arf) correlated with percentage of SAß-gal expressing cells after wsCSE treatment. The antioxidant N-acetyl-L-cysteine (NAC) prevented ROS-induced DNA damage and phosphorylation of p38 MAPK, whereas activation of ASK1 and increased expression of p19(Arf) were not significantly affected by NAC. CONCLUSIONS: The findings support the hypothesis that compounds in wsCSE induces amnion cell senescence via a mechanism involving ROS and DNA damage. Both pathways may contribute to PTB and pPROM. Our results imply that antioxidant interventions that control ROS may interrupt pathways leading to pPROM and other causes of PTB.
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Âmnio/metabolismo , Senescência Celular/genética , Dano ao DNA , Células Epiteliais/metabolismo , Estresse Oxidativo , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , MAP Quinase Quinase Quinase 5/metabolismo , Fosforilação , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Nicotiana/química , beta-Galactosidase/metabolismo , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
PROBLEM: Intra-amniotic pathogens and by-products activate innate immune responses encompassing multitudes of signaling molecules and pathways that can result in spontaneous preterm birth (PTB). This study investigates fetal membrane response to bacterial stimulation using a bioinformatics approach. METHOD OF STUDY: Dysregulated biomarker (IL1-ß, IL-2, IL-8, IL-10, and TNF-α) data from fetal membranes at term stimulated with Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, E. coli, Group B Streptococci, Polyporhans gingivalis, or Gardnerella vaginalis with 50% (v/v) amniotic fluid (AF) were analyzed by Ingenuity Pathway Analysis. RESULTS: In racially stratified analysis, networks representing late-stage immune inflammation were seen in African-Americans in AF absence. Inflammation was dominant in AF presence as well. In Caucasians, late-stage immune response was dominant with AF, but not in its absence. CONCLUSIONS: Fetal membrane biofunctions in response to bacteria reflect early- and late-stage innate immune defenses that vary based on the presence of AF and subject race.