Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF-ß1/Smad2/3 pathways.

This study aimed to investigate the potential anti-fibrotic activity of vinpocetine in an experimental model of pulmonary fibrosis by bleomycin and in the MRC-5 cell line. Pulmonary fibrosis was induced in BALB/c mice by oropharyngeal aspiration of a single dose of bleomycin (5 mg/kg). The remaining induced animals received a daily dose of pirfenidone (as a standard anti-fibrotic drug) (300 mg/kg/PO) and vinpocetine (20 mg/kg/PO) on day 7 of the induction till the end of the experiment (day 21). The results of the experiment revealed that vinpocetine managed to alleviate the fibrotic endpoints by statistically improving (P ≤ 0.05) the weight index, histopathological score, reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. It also alleviated tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators significantly elevated in bleomycin-only induced animals (P ≤ 0.05). Vinpocetine managed to express a remarkable attenuating effect in pulmonary fibrosis both in vivo and in vitro either directly by interfering with the classical TGF-ß1/Smad2/3 signaling pathway or indirectly by upregulating the expression of Nrf2 enhancing the antioxidant system, activating PPAR-γ and downregulating the NLRP3/NF-κB pathway making it a candidate for further clinical investigation in cases of pulmonary fibrosis.

The impact of empagliflozin and metformin on cardiac parameters in patients with mid-range ejection fraction heart failure without diabetes.

Heart failure (HF) remains a significant problem for healthcare systems, requiring the use of intervention and multimodal management strategies. We aimed to assess the short-term effect of empagliflozin (EMPA) and metformin on cardiac function parameters, including ventricular dimension-hypertrophy, septal thickness, ejection fraction (EF), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with HF and mildly reduced EF. A case-control study included 60 newly diagnosed patients with HF. Patients were divided into two groups: Group E received standard HF treatment (carvedilol, bumetanide, sacubitril-valsartan, spironolactone) plus EMPA 10 mg daily, and Group M received standard HF treatment plus metformin 500 mg daily. After three months of treatment, Group E had a significantly higher EF than Group M compared to initial measurements (a change of 9.2% versus 6.1%, respectively). We found similar results in the left ventricular end-systolic dimension (LVESD), with mean reductions of 0.72 mm for Group E and 0.23 mm for Group M. Regarding cardiac indicators, the level of NT-proBNP was considerably decreased in both groups. However, the reduction was significantly greater in group E than in group M compared to the initial level (mean reduction: 719.9 vs. 973.6, respectively). When combined with quadruple anti-heart failure therapy, metformin enhanced several echocardiographic parameters, showing effects similar to those of EMPA when used in the same treatment regimen. However, the benefits of EMPA were more pronounced, particularly regarding improvements in EF and LVESD.

The mitigating effect of para-hydroxycinnamic acid in bleomycin-induced pulmonary fibrosis in mice through targeting oxidative, inflammatory and fibrotic pathways.

This study investigated the therapeutic benefits of para-hydroxycinnamic acid in mice with bleomycin-induced lung fibrosis. Forty male BALB/c mice were randomly assigned to four groups: normal, which received 0.9% normal saline; induced, which received a single dose of bleomycin (5 mg/kg) by oropharyngeal challenge; pirfenidone-treated; and para-hydroxycinnamic acid-treated, which challenged with bleomycin and received a daily oral dose of 300 and 50 mg/kg, respectively, from day 7 to day 21. Tissue pro-fibrotic and inflammatory cytokines, oxidative indicators, pulmonary histopathology, immunohistochemistry of fibrotic proteins and the assessment of gene expression by RT-qPCR were evaluated on day 22 after euthanizing animals. Pirfenidone and para-hydroxycinnamic acid managed to alleviate the fibrotic endpoints by statistically improving the weight index, histopathological score and reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. They also managed to alleviate tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators. para-Hydroxycinnamic acid enhanced the expression of crucial genes associated with oxidative stress, inflammation and fibrosis in vivo. para-Hydroxycinnamic acid has demonstrated similar effectiveness to pirfenidone, suggesting it could be a promising treatment for fibrotic lung conditions by inhibiting the TGF-ß1/Smad3 pathway or through its anti-inflammatory and antioxidant properties.

Metformin effects on cardiac parameters in non-diabetic Iraqi patients with heart failure and mid-range ejection fraction - a comparative two-arm parallel clinical study.

Heart failure (HF) remains a difficult challenge to the healthcare system, necessitating promoting interventions and multidrug management. Metformin, typically used to manage diabetes, has emerged as a promising intervention in the treatment of HF. This study aimed to assess the effect of adding metformin to the standard treatment of HF on cardiac parameters. This clinical study comprised 60 newly diagnosed HF patients randomly assigned to two groups: Group C received standard HF treatment, while Group M received standard HF treatment in addition to daily metformin (500 mg). After 3 months of treatment, group M showed a significantly higher ejection fraction (EF) compared to Group C (6.1% and 3.2%, respectively; p-value=0.023) and a reduction in the left ventricular end-diastolic pressure (LVEDD) (0.28, and 0.21 mm respectively; p-value=0.029). No significant differences were observed in the interventricular septal thickness (IVST) or left ventricular end-systolic pressure (LVESD). For cardiac markers, N-Terminal pro-BNP (NT-proBNP) showed the highest reduction in Group M compared to Group C (719.9 pg/ml and 271.9 pg/ml respectively; p-value=0.009). No significant changes were reported for soluble ST2. Metformin demonstrated cardiac protective effects by increasing EF and reducing NT-proBNP. Given its affordability and accessibility, metformin offers a valuable addition to the current HF treatment options. This positive effect may be attributed to mechanisms that enhance the impact of conventional HF treatments or vice versa.

Effects of combined metformin and cabergoline versus metformin alone on ovarian and hormonal activities in Iraqi patients with PCOS and hyperprolactinemia: a randomized clinical trial.

Polycystic ovary syndrome (PCOS) is one of the most prevalent metabolic diseases during female reproductive life, often associated with insulin resistance and hyperprolactinemia. The efficacy of metformin and cabergoline for managing PCOS remains debated in the literature. This three-arm interventional study in Iraq assessed the effects of these drugs on body mass index (BMI), hormonal balance, and uterine artery blood flow in 75 women with PCOS and hyperprolactinemia. Participants were randomized into three groups: metformin (500 mg twice daily), cabergoline (0.5 mg weekly), and a combination of both, with 25 patients in each group. Baseline and 90-day follow-up characteristics included BMI, serum hormonal levels, and ultrasound features. Metformin resulted in significant weight reduction (p=0.038); however, the addition of cabergoline caused a more significant reduction in body mass index (p=0.001). The combined treatment significantly lowered testosterone levels (p=0.008). In addition, this combination significantly reduced the level of LH (p=0.043) and increased the level of FSH (p=0.047). The results suggest that metformin and cabergoline when used together, act synergistically and safely to reduce BMI, testosterone, and LH levels while increasing FSH levels. Furthermore, this combination improved endometrial blood flow and ovulation in women with PCOS.

Assessment of adherence level for neonatal hyperbilirubinemia management by various physicians in Iraq: a multi-clinic study.

Background: Neonatal jaundice is a physiological process that occurs normally for every infant to a varying degree. In some cases, this process becomes pathological and imposes an increased risk of morbidity and mortality for the infant. The aim of this study was to assess the adherence level of various physicians to different guidelines of management of neonatal hyperbilirubinemia in Iraq. Methods: An observational cross-sectional study was conducted in multiple outpatient clinics in various Iraqi provinces, from February 2018 to February 2019. The study involved 130 physicians, who were divided into emergency physicians (EPs), general practitioners (GPs), and pediatricians (PDs), and assessed their compliance to guidelines for management of neonatal hyperbilirubinemia using a questionnaire, which included providing the correct management for a test case scenario. Results: PDs had significantly longer discharge times compared to EPs and GPs. In total, 91.7 % of PDs always tested the neonate for bilirubin levels before discharge, while 5.5 % of GPs and 0% of EP did so. Regarding follow-up visits, 16.7 %, 4.8% and 45.2% of PDs, EPs and GPs, respectively, scheduled a follow-up between 49-72 hours; 47.6 % and 38.1% of EPs scheduled a follow-up at ≤24 hours and 25-48 hours, respectively . In addition, 91.7% of PDs gave the correct answer for the management of the test case scenario, followed by 58.9% of GPs, and 38.1% of EPs . About half of PDs extended neonates length of stay beyond 48 hours. Conclusion: GPs and EPs show lower adherence levels for the management of neonatal jaundice than PDs, which indicates that these physicians adhere well to current management guidelines from the WHO, AAP, and NICE.

Placenta accrete spectrum disorders: A single centre experience over four years in the view of international guidelines.

OBJECTIVE: To evaluate the prevalence and management strategies of placenta accreta spectrum disorders at a tertiary teaching hospital. METHODS: The retrospective cross-sectional study was conducted at Al-Yarmouk Teaching Hospital, Baghdad, Iraq, and comprised record of patients diagnosed with placenta accreta spectrum disorders between January 2014and December 2017. Different management approached employes were noted and data was analysed using SPSS 22. RESULTS: Of the 7312 deliveries during the four-year period, there were 102(1.4%) cases of placenta accreta spectrum disorders. Of them, 83(81.3%) were managed by definitive surgery and 19(18.7%) with conservative surgery. The prevalence of placenta accreta spectrum disorders was 162.4 per 100,000 women in 2014, 266.7 in 2015, 382.3 in 2016, and 191.5 per 100 000 women in 2017. All the cases related to multiparous women with previous history of caesarean section. CONCLUSIONS: The incidence of placenta accreta spectrum disorders was high in our centre.

ACE gene polymorphism and its association with serum erythropoietin and hemoglobin in Iraqi hemodialysis patients.

PURPOSE: To evaluate the frequencies of angiotensin-converting enzyme gene polymorphism in Iraqi hemodialysis patients and to examine the association between this polymorphism and serum erythropoietin and hemoglobin levels. . METHODS: In this study, 70 chronic renal failure Iraqi patients on maintenance hemodialysis (patient group) and 20 healthy subjects (control group) were genotyped for angiotensin-converting enzyme gene polymorphism. The distribution of genotype and allele frequencies of this polymorphism in these subjects were also evaluated. . RESULTS: The distribution of angiotensin-converting enzyme genotypes between groups was similar, and the ID genotype was the most frequent, followed by DD and II genotypes ( 50% , 37% , and 13%). The control group had a nonsignificant difference in serum erythropoietin levels among different angiotensin-converting enzyme genotypes, while patients with ID and DD genotypes displayed significant elevation in serum erythropoietin with time. No significant differences in hemoglobin levels were observed in patient and control groups. A significant positive correlation was observed between serum erythropoietin and hemoglobin in the control group with different angiotensin-converting enzyme genotypes, while a nonsignificant negative correlation was observed in the patient group throughout the study. . CONCLUSIONS: Chronic kidney disease did not significantly alter angiotensin-converting enzyme genotypes, and angiotensin-converting enzyme gene polymorphism had a significant effect on serum erythropoietin levels and a non significant effect on hemoglobin levels. .

Interleukin-6 gene polymorphisms and serum erythropoietin and hemoglobin in hemodialysis Iraqi patients.

Chronic kidney disease (CKD) is characterized by elevated levels of pro-inflammatory cytokines. Interleukin-6 (IL-6) is a pleiotropic and pro-inflammatory cytokine involved in different biological activities such as hematopoiesis, inflammation, and acute-phase response. The rate of IL-6 synthesis and degradation is affected by single nucleotide polymorphisms. This study aimed to evaluate the frequencies of 174G/C IL-6 gene promoter polymorphism in Iraqi hemodialysis (HD) patient and to examine the association between the allelic variations and serum erythropoietin (EPO) and hemoglobin (Hb) levels. The frequencies of IL-6 gene polymorphism were studied in 70 chronic renal failure patients on maintenance HD (patients group) and in 20 healthy participants (control group). Genotyping of IL-6 gene was performed by conventional polymerase chain reaction-restriction fragment length polymorphism. The distribution of IL-6 genotypes between groups was similar, and GG genotype is the most frequent followed by CG and CC genotypes. Control group had a nonsignificant difference in serum EPO levels among different IL-6 genotypes, while patients with GG genotype displayed significant elevation in serum EPO with time, followed by CG and CC genotypes. No significant differences in Hb levels were observed in patients and control groups. A significant positive correlation was observed between serum EPO and Hb in control group with different IL-6 genotypes, while a nonsignificant negative correlation was observed in patients group throughout the study. CKD did not significantly alter IL-6 genotypes, and IL-6 gene polymorphism had a significant effect on serum EPO levels and a nonsignificant effect on Hb levels.