Rutin Promotes Wound Healing by Inhibiting Oxidative Stress and Inflammation in Metformin-Controlled Diabetes in Rats.

Diabetes mellitus (DM) is a metabolic disorder with a notable increase in global incidence in recent years. Individuals diagnosed with diabetes are at an elevated risk of morbidity and mortality compared with the general population. For several years, the potential of phytochemicals as anti-inflammatory agents to improve the healing of diabetic wounds has been under investigation. Rutin, a flavonoid, is a particularly promising candidate for use in wound healing. Our study aims to investigate the potential impact of a topical application of rutin nanoformulation on wound healing in streptozotocin (STZ)-induced hyperglycemic rats controlled with metformin, with a focus on its anti-inflammatory and antioxidant properties. Rats are randomized into 3 groups. GI: diabetic control group; wound untreated. GII: diabetes and rutin-NP-treated wound. GIII: diabetic + ß-sitosterol-treated wound. The findings suggest that topical application of rutin-NPs has the potential to enhance the wound-healing process by attenuating oxidative stress, as evidenced by restoring GSH, CAT, and SOD antioxidants, and decreasing MDA production mediated by Nrf2 activation. Also, inflammation is suppressed, as indicated by the decreased CRP, IL-1ß, IL-6, and TNF-α levels. Molecular docking data confirm the biological data of rutin, where rutin is docked into the catalytic site of the X-ray crystallographic structures of CRP, Keap-1, IL-1ß, IL-6, and TNF-α via grid-based ligand docking. The binding affinity and binding energy of ligand-protein interactions demonstrate the affinity and binding to the specifically selected proteins.

Oral Contraceptive Types in Relation to ABO Blood Groups Among Saudi Women of Different Reproductive Age Groups and Impact on Venous Thromboembolism.

Saudi women have recently started using oral contraceptives (OCs), which has led to risk of venous thromboembolism (VTE). The risk varies with the type of OC generations used, and with OC use the risk for VTE increases by 2- to 6-fold. This study evaluated the effect of OC types in relation to ABO blood group on the risk of VTE among Saudi women. Thrombin generation (TG) was measured in the plasma of the women in the presence and absence of platelet rich plasma, platelet poor plasma and thrombomodulin or activated protein C. OC usage increased TG parameters ETP and Peak height by 9.81% and 16.04%, respectively. An increased risk of VTE was seen among women on third generation OCs as compared to those on second generation products. Within OC generations, we found that for women using fourth generation OCs, their ETP increased by 36.18% as compared to those using second generation and by 6.07% in those using third generation compared to those using second generation. There was significant difference with respect to ABO blood groups and OC generation types, but larger sample size is required. Women who are 40 years and older and using third generation OC had a higher risk of having thrombosis (11.84%), as compared to those using second generation OC (8.79%) and to those using fourth generation OC (5.03%). An association between different OC groups and non-O blood group in thrombosis generation was noted. TG parameters were significantly increased in relation to BMI when comparing to OC users versus non-users. In addition, inhibition of TG parameters in the presence of recombinant human thrombomodulin (TM) and activated protein C (APC) were significantly increased.

The effects of oral contraceptive usage on thrombin generation and activated protein C resistance in Saudi women, with a possible impact of the body mass index.

BACKGROUND AND OBJECTIVES: The effect of oral contraceptive (OC) usage on coagulation has been studied worldwide. However, no such studies have been conducted in Saudi Arabia on Saudi women using OCs. The aim of this study was to investigate the effects of OC-induced changes of thrombin generation (TG) in the absence and presence of activated protein C (APC) or thrombomodulin (TM) in Saudi women. METHODS: A total of 115 adult women, 47 on oral contraception (OC users) and 68 controls (not using OCs) were recruited from the obstetrics-gynecology outpatient clinic in Saudi Arabia. OCs that were used in this study include the following: Marvelon, Gynera, Cerrazetem, Yasmine, Microlut, Gracial and Diane. The plasma calibrated automated thrombinography (CAT) was used to determine TG which was expressed as endogenous thrombin potential (ETP; nM/min), lag time (min), peak (nM) and time-to-peak (ttpeak; min). In the presence of TM or APC, TG parameters were expressed relative to the parameters in the absence of TM or APC. RESULTS AND CONCLUSION: As in other populations, our study demonstrated that OC usage induced prothrombotic changes in plasma of Saudi women, including resistance to the inhibitory actions of TM and APC. More specifically, OC usage in our population predominantly influenced TG and APC/TM sensitivity in overweight and obese individuals, a finding that needs confirmation in large cohort studies. The effects of APC and TM on TG parameters showed a positive association, and the correlation coefficients were higher in OC users for both ETP and peak values.

Thrombin Generating Capacity and Phenotypic Association in ABO Blood Groups.

Individuals with blood group O have a higher bleeding risk than non-O blood groups. This could be explained by the lower levels of FVIII and von Willebrand Factor (VWF) levels in O individuals. We investigated the relationship between blood groups, thrombin generation (TG), prothrombin activation and thrombin inactivation. Plasma levels of VWF, FVIII, antithrombin, fibrinogen, prothrombin and α2Macroglobulin (α2M) levels were determined. TG was measured in platelet rich (PRP) and platelet poor plasma (PPP) of 217 healthy donors and prothrombin conversion and thrombin inactivation were calculated. VWF and FVIII levels were lower (75% and 78%) and α2M levels were higher (125%) in the O group. TG is 10% lower in the O group in PPP and PRP. Less prothrombin was converted in the O group (86%) and the thrombin decay capacity was lower as well. In the O group, α2M plays a significantly larger role in the inhibition of thrombin (126%). In conclusion, TG is lower in the O group due to lower prothrombin conversion, and a larger contribution of α2M to thrombin inactivation. The former is unrelated to platelet function because it is similar in PRP and PPP, but can be explained by the lower levels of FVIII.