Protein C and protein S deficiencies are associated with increased risk of deep vein thrombosis in pregnant women using oral contraceptives.

BACKGROUND: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE). OBJECTIVE: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT). MATERIALS AND METHODS: This case-control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives). The levels of PC, PS, and antithrombin were measured and compared between the two groups. The use of different types of oral contraceptives and their association with DVT and PC and PS were also analyzed. RESULTS: The study found that women with DVT had significantly lower levels of PC and PS compared with controls ( P  < 0.001). However, no significant difference was found in the levels of AT. Among the different types of oral contraceptives, first-generation progestin pills including Ethynodiol Diacetate, Norethindrone Acetate, Norethynodrel, and second-generation oral contraceptives (Lynestrenol, Levonorgestrel and Norgestrel) were not found to be associated with lower levels of PC and AT while Desogestrel, Norgestimate, and Gestodene (third-generation) were associated with lower levels of PS. CONCLUSION: This study suggests that the use of contraceptives, particularly those containing Desogestrel, Norgestimate, and Gestodene, may be associated with a higher risk of thrombosis because of the associated lower levels of PS. Monitoring anticoagulant levels is crucial in preventing DVT in this population.

Actinidia deliciosa Extract as a Promising Supplemental Agent for Hepatic and Renal Complication-Associated Type 2 Diabetes (In Vivo and In Silico-Based Studies).

Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as a promising approach for the treatment of diabetes and its complications. Kiwifruit is recognized for its substantial content of antioxidative phenolics. Therefore, this work aimed to examine the effect of Actinidia deliciosa (kiwi fruit) on hepatorenal damage in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2D in rats using in vivo and in silico analyses. An increase in hepatic and renal lipid peroxidation was observed in diabetic rats accompanied by a decrease in antioxidant status. Furthermore, it is important to highlight that there were observable inflammatory and apoptotic responses in the hepatic and renal organs of rats with diabetes, along with a dysregulation of the phosphorylation levels of mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K) signaling proteins. However, the administration of kiwi extract to diabetic rats alleviated hepatorenal dysfunction, inflammatory processes, oxidative injury, and apoptotic events with activation of the insulin signaling pathway. Furthermore, molecular docking and dynamic simulation studies revealed quercetin, chlorogenic acid, and melezitose as components of kiwi extract that docked well with potential as effective natural products for activating the silent information regulator 1(SIRT-1) pathway. Furthermore, phenolic acids in kiwi extract, especially syringic acid, P-coumaric acid, caffeic acid, and ferulic acid, have the ability to inhibit the phosphatase and tensin homolog (PTEN) active site. In conclusion, it can be argued that kiwi extract may present a potentially beneficial adjunctive therapy approach for the treatment of diabetic hepatorenal complications.

Diagnostic Performance of Anti-Müllerian Hormone, Luteinizing Hormone to Follicle-Stimulating Hormone Ratio, Testosterone, and Prolactin to Predict Polycystic Ovary Syndrome Among Sudanese Women.

Background: Polycystic ovary syndrome (PCOS) is one of the most important contributing factors to infertility. The diagnosis of PCOS is not an easy procedure, as the signs and symptoms are heterogeneous and of undefined etiology. There are only a few published studies that address the diagnostic performance of anti-Müllerian hormone in diagnosis of PCOS in sub-Saharan Africa including Sudan. Objective: This study aims to assess anti-Müllerian hormone (AMH), luteinizing to follicle-stimulating hormone ratio (LH: FSH), total testosterone (TT), and prolactin (PRL) levels among PCOS. In addition, we determine if AMH can be used as a predictor of PCOS among Sudanese women. Methods: There were 600 women enrolled in this observational cross-sectional study, 300 of whom had PCOS, and 300 of whom healthy women; PCOS was diagnosed using the Rotterdam criteria. On days 2-4 of the menstrual cycle, serum LH, FSH, AMH, TT, and PRL levels were measured for all participants. Diagnostic performance of these parameters for PCOS was determined by receiver operating characteristic (ROC) curve. Results: Significantly higher means among PCOS regarding their BMI, AMH; LH: FSH ratio; TT; PRL, whereas significantly inverse in FSH compared with normal ovulatory women. On ROC analysis, AMH had the largest operating characteristic curve at cut-off >3.95 ng/mL; AUC = 0.999 with Youden's index 0.99%, followed by LH: FSH ratio at cut-off 0.749; AUC=0.932; Youden's index 0.813%, TT cut-off 0.82 mIU/L, AUC=0.852 with Youden's index 0.58, while PRL showed the lowest AUC=0.627 with cut-off 15.3 ng/mL, Youden's index was 0.18%, P. value<0.001. Conclusions: Sudanese women with PCOS had higher serum AMH level, LH:FSH ratio, and TT level. Moreover, AMH level has better discriminative power and good diagnostic potency for the diagnosis of PCOS among Sudanese.

IL-10 rs1800896 Polymorphism: A Risk Factor for Adult Acute Lymphoblastic Leukemia.

Purpose: Single-nucleotide polymorphism (SNP) in the promoter region of the IL-10 gene can increase susceptibility to tumor development. The current study aimed to explore the genotypic frequency of interleukin-10 (IL-10) rs1800896 polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and validate whether this SNP is a risk factor for adult ALL. Patients and Methods: This case-control study was based on a subset of newly diagnosed 154 adult patients with ALL recruited from the Radiation and Isotope Center in Khartoum (RICK) and 154 healthy controls from the same geographical area. Genomic DNA was used for the genotyping of rs1800896 polymorphism through allele-specific polymerase chain reaction (PCR) assays. Results: The genotypic frequencies of rs1800896 showed a statistically significant association of AG and AA genotypes with adult ALL (p<0.001). Combined genotypes AG+GG vs AA also showed a positive association of rs1800896 with adult ALL (OR=4.89). The allelic frequencies of G and A did not show any significant difference in adult patients with ALL compared with the control group. AG rs1800896 genotype showed an increased risk of B and T ALL (OR=2.51 and 4.70, respectively). Age at diagnosis, gender, and immunophenotype (B vs T ALL) did not exhibit any association of rs1800896 with ALL in this patient group. Conclusion: rs1800896 polymorphism is associated with an increased risk of ALL in adult patients irrespective of the age at diagnosis, gender, and immunophenotype of ALL.

New insights into geraniol's antihemolytic, anti-inflammatory, antioxidant, and anticoagulant potentials using a combined biological and in silico screening strategy.

The study aims to assess the antihemolytic and antioxidant activities of geraniol versus 2, 2'-azobis, 2-amidinopropane dihydro-chloride- (AAPH-) induced oxidative damage and hemolysis to erythrocytes and its anti-inflammatory potential against lipopolysaccharide- (LPS-) induced inflammation in white blood cells (WBCs) with a focus on its integrated computational strategies against different targeted receptors participating in inflammation and coagulation. The rats' erythrocyte suspension was incubated with different geraniol concentrations. Molecular docking and simulation were used to explore the possible interaction patterns of geraniol against the potential targeted proteins for therapeutic screening. The results displayed that geraniol had a prolonged noteworthy effect on activated partial thromboplastin time and thromboplastin time. Geraniol displayed strong antioxidant effects via reduced malondialdehyde (MDA) formation and increased GSH level and SOD activity. We observed dose-dependent prevention of K+ ion leakage along with a remarkable decline of hemolysis in erythrocytes pretreated with geraniol. Geraniol 100 µg/mL and diclofenac 100 µM were nontoxic to WBCs. Geraniol significantly reduces the expression and release of cellular pro-inflammatory factors TNF-α, IL-1ß, IL-8, and nitric oxide, accompanied by a significant upregulation of gene expression of anti-inflammatory cytokine IL-10 in LPS-induced WBCs compared to nontreated cells. It demonstrates a much stronger inhibition potential than diclofenac in terms of inflammation inhibition. When comparing molecular docking and simulation data, current work showed that geraniol has a good affinity toward apoptosis signal-regulating kinase 1 (ASK1) and human P2Y12 receptors and could be developed as an antioxidant, anti-inflammatory, and anticoagulant medication in the future. Consequently, geraniol is recommended to have a defensive influence against oxidative stress, and hemolysis also could be developed as a promising anti-inflammatory, antioxidant, and anticoagulant medication.

Assessment of risk factors for deep vein thrombosis associated with natural anticoagulants and fibrinolytic regulatory proteins.

Deep vein thrombosis (DVT) is a critical condition and a potential cause of mortality and morbidity in Africa and worldwide with a high recurrence rate. The study was designed to assess the roles of natural anticoagulants and fibrinolytic regulatory factors in the development of DVT in Sudanese patients. A case-control study was conducted in Omdurman Teaching Hospital, Khartoum State over a period of 1 year. The study enrolled 200 patients diagnosed with DVT and 200 age-matched and gender-matched controls. Demographic data and data on acquired risk factors were collected using a semi-structured questionnaire. Protein C (PC), protein S (PS), antithrombin III (AT-III), thrombin-activable fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor-1 (PAI-1) were measured in patients and controls. Among the patients with DVT, 5.5% had PC deficiency, 8.5% had PS deficiency, and 3% had AT-III deficiency. Elevated TAFI and PAI-1 levels were demonstrated in 1.5 and 0.5% of patients, respectively. Risk factors for DVT (overweight, surgical history, and family history of DVT) were remarkably higher in patients than in controls. Among the female participants, pregnancy and usage of oral contraceptive pills were the highest associated risk factors for DVT. The findings concluded that the early assessment of risk factors, including the measurements of natural inhibitors, can predict the occurrence of DVT before it is actually detected in patients.

Age- and Gender-Independent Association of XRCC1 Arg399Gln Polymorphism with Chronic Myeloid Leukemia.

PURPOSE: DNA damage to hematopoietic progenitor cells is an essential factor for leukemia development as a failure of the host DNA repair system to fix errors in DNA. This study aimed to assess the association of XRCC1 gene polymorphisms including Arg194Trp, Arg399Gln, and Arg280His with the risk of development of CML in Sudanese population. PATIENTS AND METHODS: The present study was conducted on 186 newly diagnosed patients with CML, aged 19-70 years (118 males and 68 females; mean age of 46.15±13.91 years) and 186 normal healthy controls (123 males and 63 females; mean age of 44.94±8.97 years). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the XRCC1 (Arg194Trp, Arg399Gln, and Arg280His) gene polymorphisms. RESULTS: The genotypic frequencies of Arg399Gln polymorphism in cases were 131 (70.4%) homozygous Arg/Arg, 46 (24.7%) homozygous Gln/Gln, and 9 (4.8%) heterozygous Arg/Gln as compared to the controls ie, 153 (82.3%), 73 (14.5%), and 6 (3.2%), respectively. The Arg399Gln variant genotypic frequencies significantly differed between the cases and controls (χ 2 = 7.249, P = 0.027). By comparison, no statistically significant difference was observed in the variant genotype frequencies between the cases and controls in terms of Arg194Trp and Arg280His polymorphisms. CONCLUSION: XRCC1 Arg399Gln gene polymorphism might have an important role in increasing the risk of chronic myeloid leukemia among Sudanese patients. Furthermore, all tested three polymorphisms showed no association of risk of the development of CML with age and gender.

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia.

PURPOSE: Glutathione S-transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML. PATIENTS AND METHODS: This case-control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers. RESULTS: GSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys. CONCLUSION: In conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.

Cost effectiveness of adopted quality requirements in hospital laboratories.

BACKGROUND: The present study was designed in quasi-experiment to assess adoption of the essential clauses of particular clinical laboratory quality management requirements based on international organization for standardization (ISO 15189) in hospital laboratories and to evaluate the cost effectiveness of compliance to ISO 15189. METHODS: The quality management intervention based on ISO 15189 was conceded through three phases; pre - intervention phase, Intervention phase and Post-intervention phase. RESULTS: In pre-intervention phase the compliance to ISO 15189 was 49% for study group vs. 47% for control group with P value 0.48, while the post intervention results displayed 54% vs. 79% for study group and control group respectively in compliance to ISO 15189 and statistically significant difference (P value 0.00) with effect size (Cohen's d) of (0.00) in pre-intervention phase and (0.99) in post - intervention phase. The annual average cost per-test for the study group and control group was 1.80 ± 0.25 vs. 1.97 ± 0.39, respectively with P value 0.39 whereas the post-intervention results showed that the annual average total costs per-test for study group and control group was 1.57 ± 0.23 vs 2.08 ± 0.38, P value 0.019 respectively, with cost-effectiveness ratio of (0.88) in pre -intervention phase and (0.52) in post-intervention phase. CONCLUSION: The planned adoption of quality management requirements (QMS) in clinical laboratories had great effect to increase the compliance percent with quality management system requirement, raise the average total cost effectiveness, and improve the analytical process capability of the testing procedure.