Drug Utilization Evaluation Study of Ciprofloxacin Use and Adverse Events Occurrence: Role of Community Pharmacists.

Background: Antimicrobial resistance is a global health crisis threatening optimal management of infectious diseases. Ciprofloxacin is a widely used fluoroquinolone in various disease conditions. Resistance against ciprofloxacin is increasing, leading to nonoptimal management of patients. Thus, the aim of this study was to assess ciprofloxacin use in the community setting in terms of appropriate prescribing, dosing, frequency, and duration of use. Methods: A cross-sectional, retrospective study was conducted by community pharmacists in 5 community pharmacies in Egypt from September 2021 to February 2022. Patients prescribed oral ciprofloxacin during the period of the study were included. Data on demographics, indications for ciprofloxacin, dosing regimen, adverse events, and drug interactions were collected. Results: A total of 151 patients' record indicated for ciprofloxacin were included in the study, of whom 44.4% were men and 55.6% were women who were neither pregnant nor lactating. Based on international guidelines, 96.69% ciprofloxacin prescriptions were appropriate; 96.03% contained correct ciprofloxacin dosing whereas 3.97% were overdose. A total of 90. 73% had correct frequency of administration and 96.03% records had correct durations. Only 1.99% of patients were ≤18 years of age, which is an absolute contraindication. Interacting drugs with ciprofloxacin were 28.5% with acetaminophen, 31.1% with ibuprofen, 16.6% with antacids, 21.2% with chlorpheniramine, and 7.9% with prednisolone. Adverse events included 1.32% hypoglycemia, 0.66% hyperglycemia, 3.97% tendinitis, and 2.65% QTc (heart rate-corrected QT interval) prolongation. Conclusion and relevance: Ciprofloxacin use in community pharmacies is appropriate according to international guidelines. Ongoing drug utilization evaluation is necessary to ensure rational drug use, which in turn can decrease resistance rates.

Effect of coadministration of omega-3 fatty acids with glimepiride on glycemic control, lipid profile, irisin, and sirtuin-1 in type 2 diabetes mellitus patients: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is caused by insulin resistance or tissue insensitivity to insulin, as well as relative insulin insufficiency. Diabetes that is uncontrolled for an extended period of time is linked to substantial comorbidities and organ damage. The purpose of the current study is to assess the effect of coadministration of omega-3 fatty acids with glimepiride on blood glucose, lipid profile, serum irisin, and sirtuin-1 levels in T2DM patients. METHODS: This clinical trial involved 70 type 2 diabetic patients randomly assigned to glimepiride 3 mg with either omega-3 capsules contained fish oil 1000 mg, 13% of eicosapentaenoic acid (EPA) and 9% docosahexaenoic acid (DHA) (omega-3 group, n = 35) or placebo capsules contained corn oil and linoleic acid (control group, n = 35) daily for three months. Blood samples were obtained at the start of the study and 12 weeks later for biochemical examination of HbA1c%, FBG, fasting insulin, and lipid profile. In addition, the atherogenic index of plasma (AIP) was calculated. Human enzyme-linked immunosorbent assay (ELISA) kits were utilized for assessing serum irisin and sirtuin-1 levels before and after the intervention. RESULTS: Compared to the control group, omega-3 fatty acids decreased serum fasting blood glucose (FBG, p < 0.001), glycated hemoglobin percent (HbA1C%, p < 0.001), total cholesterol (TC, p < 0.001), triglycerides (TGs, p = 0.006), low density lipoprotein (LDL, p = 0.089), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, p = 0.021) after three months of intervention. However, a significant increase was reported in serum irisin and high density lipoprotein (HDL) between both groups after intervention (p = 0.026 and p = 0.007, respectively). The atherogenic index of plasma (AIP) increased in the control group but decreased in the omega-3 group, with significant differences between the two groups (p < 0.001). CONCLUSION: The present study found that supplementing with omega-3 fatty acids might dramatically enhance blood irisin levels, as well as improve glycemic control and lipid profile in type 2 diabetes mellitus patients using glimepiride. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov under identifier NCT03917940 . (The registration date: April 17, 2019).

Association between echocardiographic features and inflammatory biomarkers with clinical outcomes in COVID-19 patients in Saudi Arabia.

Background: Respiratory infections are one of the most common comorbidities identified in hospitalized patients. The coronavirus disease 2019 (COVID-19) pandemic greatly impacted healthcare systems, including acute cardiac services. Aim: This study aimed to describe the echocardiographic findings of patients with COVID-19 infections and their correlations with inflammatory biomarkers, disease severity, and clinical outcomes. Methods: This observational study was conducted between June 2021 and July 2022. The analysis included all patients diagnosed with COVID-19 who had transthoracic echocardiographic (TTE) scans within 72 h of admission. Results: The enrolled patients had a mean age of 55.6 ± 14.7 years, and 66.1% were male. Of the 490 enrolled patients, 203 (41.4%) were admitted to the intensive care unit (ICU). Pre-ICU TTE findings showed significantly higher incidence right ventricular dysfunction (28 [13.8%] vs. 23 [8.0%]; P = 0.04) and left ventricular (LV) regional wall motion abnormalities (55 [27.1%] vs. 29 [10.1%]; p < 0.001) in ICU patients compared to non-ICU patients. In-hospital mortality was 11 (2.2%), all deaths of ICU patients. The most sensitive predictors of ICU admission (p < 0.05): cardiac troponin I level (area under the curve [AUC] = 0.733), followed by hs-CRP (AUC = 0.620), creatine kinase-MB (AUC = 0.617), D-dimer (AUC = 0.599), and lactate dehydrogenase (AUC = 0.567). Binary logistic regression showed that reduced LV ejection fraction (LVEF), elevated pulmonary artery systolic pressure, and dilated right ventricle were echocardiographic predictors of poor outcomes (p < 0.05). Conclusion: Echocardiography is a valuable tool in assessing admitted patients with COVID-19. Lower LVEF, pulmonary hypertension, higher D-dimer, C-reactive protein, and B-type natriuretic peptide levels were predictors of poor outcomes.

Functional capacity and inflammatory biomarkers as predictors for right atrial volume index in COPD patients.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and right-heart complications. So, this study aimed to evaluate the role of right atrial volume index (RAVI), inflammatory biomarkers and functional capacity in predicting poor outcomes for patients with COPD, classified by COPD assessment test (CAT) questionnaire, as early predictors of right heart diseases. METHODS: 151 patients with COPD with ejection fraction (LVEF) > 55% were enrolled and classified according to CAT questionnaire into CAT ≥ 10 (group I) and CAT < 10 (group II). RAVI was calculated using Echocardiography. Assessment of RV systolic function was done by Doppler imaging. Functional capacity parameters were assessed by modified medical research council dyspnea scale (mMRC). IL-1ß, adiponectin, hs-CRP and neopterin were evaluated by ELSA kits. RESULTS: Group I (CAT ≥ 10) had higher RAVI (73.92 ± 21.20 ml/m2 vs 22.73 ± 6.24 ml/m2, p < 0.001), lower S`tri (0.05 ± 0.01 vs 0.13 ± 0.03 m/s, p < 0.001), lower tricuspid annular plane systolic excursion (TAPSE) (1.20 ± 0.17 cm vs 2.17 ± 0.48 cm, p < 0.001), higher RVSP (54.88 ± 7.97 vs 26.79 ± 9.84 mmHg, p < 0.001) compared with group II (CAT < 10). RAVI was good predictor of CAT (r = 0.954, p < 0.001) and strongly correlated with tricuspid S`tri, RVSP, tricuspid E/e' and Mitral E/e' (r = -0.737, r = 0.753, r = 0.817 and r = 0.515, respectively, p < 0.001). RAVI was correlated with TAPSE (r = -0.673, p < 0.001) and with tricuspid E/A ratio & LVEF (r = 0.628, r = -0.407, respectively, p < 0.001). Hs-CRP: 2.50 ± 1.43 vs 2.03 ± 1.19, IL-1ß: 37.96 ± 14.35 vs 27.57 ± 8.06, neopterin: 91.37 ± 17.30 vs 76.90 ± 16.75, p < 0.05) were significantly higher besides lower adiponectin levels (3.19 ± 1.98 vs 5.32 ± 1.33 p < 0.05) in group I as compared to group II. CONCLUSION: Functional capacity might be useful predictor for right heart diseases in COPD patients. Inflammatory biomarkers, low adiponectin and high Hs-CRP, IL-1ß and neopterin levels, might not only be useful to monitor treatment response but may also help to discriminate patients with a worsen prognosis.

Comparative study of Dapagliflozin versus Glimepiride effect on insulin regulated aminopeptidase (IRAP) and interleukin-34 (IL-34) in patient with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is one of the most common diseases, that managed by several medications such as Glimepiride and Dapagliflozin. This study aims to compare the effects of Dapagliflozin versus Glimepiride on glycemic control, insulin resistance, and biomarkers as (extracellular domain of insulin regulated aminopeptidase) IRAPe, (interleukin-34) IL-34, and (N-terminal pro b-type natriuretic peptide) NT-proBNP. This study included 60 type 2 diabetic patients, who are randomized to receive either Glimepiride 4 mg/day (group 1) or Dapagliflozin 10 mg/day (group 2). Blood samples were collected at baseline and after 3 months of treatment for biochemical analysis. Additionally, HOMA-IR is calculated. After 3 months of receiving the intervention, there is no significant difference between the effects of Glimepiride and Dapagliflozin on FBG, PPBG, HbA1C%, fasting insulin, and HOMA-IR. The difference between both groups is significant for IL-34 (p = 0.002) and non-significant for IRAPe (p = 0.12) and NT-Pro BNP (p = 0.68). Both Glimepiride and Dapagliflozin significantly improve glycemic control, and HOMA-IR with no significant difference between them. Both drugs significantly improved the level of NT-proBNP. Dapagliflozin has a borderline significant effect on IRAPe but not IL-34, and Glimepiride has significant effect on IL-34 but not IRAPe. Clinical Trial Registration: This trial was registered on clinicaltrial.gov (NCT04240171).

L-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress.

Trazodone (TRZ) is an antidepressant drug which widely used to treat insomnia, but it has a cardiotoxic effect which considered one of the TRZ limitations. The aim of this study was to investigate the protective role of L-carnitine in rats against TRZ-induced cardiotoxicity, as well as to look into the molecular mechanisms underlying its cardioprotective effects via autophagy-mediated cell death and oxidative stress. Male albino rats were randomized into four experimental groups (n = 8): normal control, TRZ group (TRZ, 20 mg/kg/day), L-carnitine group (LC, 200 mg/kg/day), and Co-treated group (L-carnitine and TRZ). All treatments were administered via oral gavage for 4 weeks. Cardiac enzymes (AST & CK-MB) and serum cardiac troponin T(cTnI) were assessed. Oxidative stress biomarkers in heart tissue (malondialdehyde; MDA, total thiol, and catalase activity) were measured. Autophagy related-genes (ATG-5 and Beclin-1), P62, and TNF-α were quantified. AST and CK-MB and cTnI significantly (p < 0.001) were increased with enhanced autophagy as well as severe histopathological changes which were manifested as scattered chronic inflammatory cells with focal fragmentation of myocardial fibers and loss of nuclei in TRZ-treated group. However, daily administration of L-carnitine (200 mg/kg) for 28 days completely reversed TRZ-induced the increased cardiac enzymes, autophagy, and myocardial inflammatory processes to the normal values. TRZ administration might have the potential to cause cardiotoxic effects that can be treated with L-carnitine administration.

Role of neopterin as an inflammatory biomarker in congestive heart failure with insights on effect of drug therapies on its level.

Inflammation has a major role in the pathogenesis of heart failure (HF). It triggers a cascade that leads to the release of pro-inflammatory cytokines which in turn cause cardiac hypertrophy, fibrosis, apoptosis, negative inotorpy and leukocyte recruitment which worsen the condition. Neopterin is an inflammatory biomarker which is released as a response to macrophage activation. Levels of neopterin are elevated in conditions which has an immunological component such as autoimmune disease, viral and bacterial infections and malignancy. Neopterin levels were found to be elevated in patients with HF. This is due to the fact that inflammation takes place during the development of the condition. Studies demonstrated that neopterin can be used as a biomarker for diagnosing HF, determining severity of the disease and monitoring its progression. Neopterin levels were higher in patients with New York Heart Association classification (NYHA) III-IV more than class I-II. Moreover, neopterin levels correlated well with morbidity and mortality. It has been suggested that neopterin be monitored levels to determine effectiveness of HF treatment options.

Folic acid effect on homocysteine, sortilin levels and glycemic control in type 2 diabetes mellitus patients.

AIM: The present study aimed to determine the folic acid supplement (FAS) effects on serum homocysteine and sortilin levels, glycemic indices, and lipid profile in type II diabetic patients. METHOD: A double-blind randomized controlled clinical trial have been performed on 100 patients with T2DM randomly divided into two groups that received either placebo or folic acid 5 mg/d for 12 weeks. RESULTS: FAS caused a significant decrease in homocysteine and sortilin serum levels (28.2% and 33.7%, P < 0.0001, respectively). After 3 months of intervention, 8.7% decrease in fasting blood glucose (P = 0.0005), 8.2% in HbA1c (P = 0.0002), 13.7% in serum insulin (P < 0.0001) and 21.7% in insulin resistance (P < 0.0001) were found in the folic acid group, however no significant difference was observed in the placebo group. Serum hs-CRP level showed significant positive associations with sortilin (r = 0.237, P = 0.018), homocysteine (r = 0.308, P = 0.002) and fasting blood glucose (r = 0.342, P = 0.000). There were no significant changes in lipid profile in both groups after 12 weeks. CONCLUSION: FAS might be beneficial for reducing homocysteine and sortilin levels, enhancing glycemic control, and improved insulin resistance in patients with T2DM.

Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients.

BACKGROUND AND OBJECTIVE: Paclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer. PATIENTS AND METHODS: This randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group (n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group (n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months. Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t-test, Mann-Whitney U test, and chi-square test. RESULTS: As compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9th and 12th weeks of paclitaxel intake (p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin (p < 0.05) as compared to baseline data and placebo. CONCLUSION: Alpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03908528.

Clinical comparative study assessing the effect of ivabradine on neopterin and NT-Pro BNP against standard treatment in chronic heart failure patients.

PURPOSE: Heart rate reduction (HR) is a cornerstone in heart failure therapy as it improves patient outcomes. The aim of this study is to evaluate short-term effect of ivabradine on NT-Pro BNP and neopterin in heart failure patients and assess the association between HR and these biomarkers. METHODS: Sixty patients on standard heart failure therapy were randomly allocated into ivabradine group (n = 30) and non-ivabradine group (n = 30). Ivabradine 5 mg twice daily was given for 3 months. Lipid profile and kidney functions were performed and blood samples for NT-Pro BNP and neopterin were analysed at baseline and after 3 months of intervention in both groups. RESULTS: There was a significant improvement in NYHA class in ivabradine group (p < 0.001). Ejection fraction was improved in ivabradine and non-ivabradine groups after intervention (p < 0.001), with a greater improvement in ivabradine group (p = 0.026). Heart rate was reduced in ivabradine group (p < 0.001) and non-ivabradine group (p < 0.001) yet greater reduction was seen in ivabradine group (p < 0.001). Serum creatinine and blood urea nitrogen were reduced in ivabradine group (Scr: p = 0.001, BUN: p = 0.001). NT-Pro BNP and neopterin levels significantly decreased in ivabradine group (NT-Pro BNP: p < 0.001, neopterin p < 0.001). Significant positive correlation was found between HR and biomarker levels after intervention (NT-Pro BNP: r = 0.475, p < 0.001, neopterin: r = 0.384, p = 0.002). CONCLUSION: Ivabradine therapy reduced levels of both biomarkers which correlated well with HR. Biomarker levels might provide a tool for assessing ivabradine effectiveness in HF. Trial registration Date: June 26, 2020. Identifier: NCT04448899. Link: Ivabradine in Patients with Congestive Heart Failure-Full Text View-ClinicalTrials.gov.

Omega 3 fatty acids effect on the vascular calcification biomarkers fetuin A and osteoprotegerin in hemodialysis patients.

Chronic renal failure patients on dialysis are at a high risk of death due to vascular calcification. This study aimed at investigating the effect of omega-3 fatty acids on the vascular calcification biomarkers fetuin-A and osteoprotegerin (OPG) in patients with chronic renal failure who are undergoing hemodialysis. This prospective, open-label, controlled, parallel study included 60 hemodialysis patients who were randomized to receive either omega-3 fatty acids capsule along with their standard care of treatment (omega-3 group) or their standard care of treatment only (control group). Serum levels of fetuin-A, OPG, calcium, phosphorus, hemoglobin, parathyroid hormone, blood urea nitrogen (BUN), albumin, serum creatinine (SCr), and serum triglycerides (TG) were measured at baseline and after six months of intervention and follow-up of both groups. Significantly increased levels of fetuin-A and OPG (p < 0.001) were observed in the omega-3 group six months after the intervention compared with the control group. Levels of TG, albumin, SCr, BUN, phosphorous, calcium, hemoglobin, and parathyroid hormone were not significantly different in the omega-3 group compared with the control group after six months of intervention. Our study concluded that omega-3 may have a clinically beneficial effect in decreasing cardiovascular events by increasing the levels of the protective vascular calcification inhibitors fetuin-A and osteoprotegerin in chronic renal failure patients who are undergoing hemodialysis.

l-carnitine modulates autophagy, oxidative stress and inflammation in trazodone induced testicular toxicity.

BACKGROUND: Trazadone is an antidepressant and may affect reproductive hormones and spermatogenesis. l-carnitine is an amino acid that exhibits antioxidant actions. This study was designed to investigate the potential protective effects of l-carnitine against trazadone-induced testicular toxicity in male rats and the possible underlying mechanisms such as oxidative stress, inflammation and autophagy. METHODS: thirty-two male Wistar rats were divided randomly into four equal groups (n = 8). Testicular damage was induced by oral administration of Trazadone (TRZ, 20 mg/kg/day, p.o.) for four weeks (TRZ group). l-carnitine (LC, 200 mg/kg/day, p.o.) was applied for four weeks (LC group). LC + TRZ group administered the same doses of LC and TRZ concomitantly. The control group received distilled water (as vehicle). RESULTS: the protective treatment with LC attenuated the decline of sperm count and motility resulted from trazadone administration. Moreover, LC ameliorated trazadone increased lipid peroxidation (MDA) and reduction of total thiol and catalase activity. LC modulated the elevation in tumor necrosis factor- α (TNF-α), and increased the expression of autophagy related genes Becline-1, ATG 5 and ATG-12 in rat testes. Serum level of FSH, LH and total testosterone were increased significantly (p < 0.001) in LC + TRZ group. Histopathological findings further supported the protective effects of LC against trazadone -induced testicular injury by increasing free sperms within the lumen of spermatogenic cells and improving testicular degeneration. CONCLUSION: These findings supported the protective effects of l-carnitine on rat testes due to suppression of oxidative stress, inflammation and enhancing autophagy. l-carnitine may be recommended as adjuvant therapy to trazadone treatment.

Candesartan protects against d-galactose induced - Neurotoxicity and memory deficit via modulation of autophagy and oxidative stress.

PURPOSE: d-galactose induces neuroinflammation and memory deficit via oxidative stress. Candesartan is an angiotensin II-receptor blocker and has proved neuroprotective properties. This study aimed to investigate the neuroprotective effect of candesartan against d-galactose induced neuroinflammation and memory deficit via autophagy. METHODS: Twenty-eight male Wistar rats aged 3 months were divided into four equal groups: control (vehicle), d-gal (100 mg/kg d-galactose), cand (1 mg/kg candesartan), and cand+d-gal (100 mg/kg d-galactose & 1 mg/kg candesartan). All treatments were given orally and daily for 4 weeks. Assessment of memory was done using Morris water maze (MWM) test. Brain tissue was assessed for malondialdehyde (MDA), total thiol, catalase activity, glial fibrillary acidic protein (GFAP) and gene expression of TNF-α, GDNF-1 as well as autophagy genes (Beclin 1 and ATG 5). RESULTS: Prophylactic treatment of candesartan in d-galactose-treated rats significantly (p < 0.001) reduced oxidative stress via reduction of MDA as well as elevation of catalase activity and total thiol levels. Additionally, candesartan prophylactic treatment significantly increased gene expression of GDNF-1 and decreased gene expression of TNF-α. Furthermore, candesartan significantly increased the expression of autophagy related gene (Beclin 1 and ATG 5) in cand+d-gal treated rats. These results were supported by the histopathological findings which showed that candesartan prevented the neuronal injury in the cerebral cortex and hippocampus and decreased GFAP positive cells of the d-galactose-treated rats. Moreover, MWM test showed that candesartan significantly improved memory deficit in cand+d-gal treated rats. CONCLUSION: Candesartan prevents d-galactose-induced neurotoxicity and memory deficit via activating autophagy and decreasing oxidative stress. Therefore, candesartan was a good candidate for age-related neurodegenerative disorders and memory deficit.

Sortilin and Homocysteine as Potential Biomarkers for Coronary Artery Diseases.

PURPOSE: The aim of this study was to assess the relationship of coronary artery disease (CAD) with levels of homocysteine and sortilin in Egyptian patients. BACKGROUND: CAD is a primary contributor to cardiac disease and a prominent cause of death globally. PATIENTS AND METHODS: We enrolled 45 patients with CAD evaluated by coronary CT angiography and 42 control subjects without CAD. Plasma-homocysteine and -sortilin levels were measured with a commercial ELISA kit. RESULTS: Elevated levels of homocysteine and sortilin were observed in the CAD patients compared to controls (13.75±1.40 vs 7.73±2.06 µmol/L, P=0 and 160.91±32.17 vs 143.02±32.30 ng/dL, P=0.02, respectively). Significantly higher total cholesterol, low density-lipoprotein cholesterol and triglycerides (P<0.05) and lower high density-lipoprotein cholesterol (P<0.05) were seen among patients with CAD than the control group. Sortilin levels were positively associated with homocysteine levels (r=0.32, P=0.006), total cholesterol (r=0.61, P=0), low density-lipoprotein cholesterol (r=0.37, P=0.001), triglycerides (r=0.91, P=0), troponin I (r=0.82, P=0), Gensini score (r=0.93, P=0) and high-sensitivity CRP (r=0.87, P=0) in all subjects. Homocysteine has a significantly negative association with high density-lipoprotein cholesterol (r=-0.42, P=0). CONCLUSION: Elevated homocysteine and sortilin levels are crucial risk factors of CAD in Egyptian patients.

The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial.

OBJECTIVE: We aimed to examine the effect of doxycycline on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage in traumatic brain injury (TBI) patients. METHODS: Patients were randomly assigned into two groups (n = 25 each) to receive either placebo or doxycycline (200 mg daily), with their standard management for 7 days. RESULTS: NSE serum levels in the doxycycline and control groups on day 3 were 14.66 ± 1.78 versus 18.09 ± 4.38 ng/mL, respectively (p = 0.008), and on day 7 were 12.3 ± 2.0 versus 16.43 ± 3.85 ng/mL, respectively (p = 0.003). Glasgow Coma Scale (GCS) on day 7 was 11.90 ± 2.83 versus 9.65 ± 3.44 in the doxycycline and control groups, respectively (p = 0.031). NSE serum levels and GCS scores were negatively correlated (r = -0.569, p < 0.001). CONCLUSION: Adjunctive early use of doxycycline might be a novel option that halts the ongoing secondary brain injury in patients with moderate to severe TBI. Future larger clinical trials are warranted to confirm these findings.

Circulating IRAPe, Irisin, and IL-34 in Relation to Insulin Resistance in Patients With Type 2 Diabetes.

PURPOSE: This study aimed to evaluate the role of the extracellular part of insulin-regulated aminopeptidase (IRAPe), interleukin (IL)-34, irisin, and visfatin in the development of insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM). METHODS: This observational parallel-group study was conducted in 60 subjects without T2DM who served as a control group and 60 patients with newly diagnosed T2DM. The 2 groups were matched for age, sex ratio, and body mass index. Anthropometric parameters; fasting blood glucose; fasting plasma insulin; Homeostatic Model Assessment for IR (HOMA-IR) index; glycated hemoglobin (HbA1c); and circulating levels of IL-34, visfatin, irisin, and IRAPe were assessed. RESULTS: The group with T2DM showed significantly higher IL-34 and visfatin levels and significantly lower irisin and IRAPe levels as compared to the healthy control group. IL-34 and visfatin were significantly positively correlated with fasting blood glucose, fasting plasma insulin, HOMA-IR, and HbA1c. On the other hand, irisin and IRAPe were significantly negatively correlated with fasting blood glucose, fasting plasma insulin, HOMA-IR, and HbA1c. IL-34 was positively associated with visfatin, while negatively associated with both irisin and IRAPe. IMPLICATIONS: IL-34, visfatin, irisin, and IRAPe may play a vital role in T2DM and in diabetes-associated IR. Additionally, IRAPe may represent a useful and direct marker for use in the detection of IR in the diabetic population. ClinicalTrials.gov identifier: NCT04107259.

Circulating IL-6, clusterin and irisin in obese subjects with different grades of obesity: association with insulin resistance and sexual dimorphism.

OBJECTIVE: There are discrepancies about the relationship of IL-6, clusterin and irisin with obesity and obesity associated insulin resistance and also about their sexual dimorphism. This study aimed at evaluating the circulating levels of IL-6, clusterin and irisin in obese subjects of both sexes who had different grades of obesity and examining their sexual dimorphism and their association with insulin resistance. METHODS: This study included 176 non-diabetic subjects of both sexes who were classified according to their sex into two groups; the male and the female groups. The male group (88 men) was classified according to BMI into; group 1 (22 lean men), group 2 (22 class I obese men), group 3 (22 class II obese men) and group 4 (22 class III obese men). The female group (88 women) was classified according to BMI exactly as the male group. Metabolic parameters, IL-6, clusterin, and irisin levels were measured. Data were analyzed by ANOVA test, post hoc Tukey's test and independent t-test. Pearson correlation was used to assess the association between variables. RESULTS: In obese subjects of both sexes, circulating IL-6, clusterin and irisin levels were significantly elevated and positively correlated with HOMA-IR. Obese males showed significantly higher HOMA-IR, IL-6, clusterin and irisin levels than obese females. CONCLUSION: Obesity in both sexes, especially in males was associated with high levels of IL-6, clusterin and irisin and worsened the metabolic pattern. Circulating IL-6, clusterin and irisin may represent possible therapeutic targets for insulin resistance in obese subjects.

Circulating IL-6, clusterin and irisin in obese subjects with different grades of obesity: association with insulin resistance and sexual dimorphism

ABSTRACT Objective: There are discrepancies about the relationship of IL-6, clusterin and irisin with obesity and obesity associated insulin resistance and also about their sexual dimorphism. This study aimed at evaluating the circulating levels of IL-6, clusterin and irisin in obese subjects of both sexes who had different grades of obesity and examining their sexual dimorphism and their association with insulin resistance. Subjects and methods: This study included 176 non-diabetic subjects of both sexes who were classified according to their sex into two groups; the male and the female groups. The male group (88 men) was classified according to BMI into; group 1 (22 lean men), group 2 (22 class I obese men), group 3 (22 class II obese men) and group 4 (22 class III obese men). The female group (88 women) was classified according to BMI exactly as the male group. Metabolic parameters, IL-6, clusterin, and irisin levels were measured. Data were analyzed by ANOVA test, post hoc Tukey's test and independent t-test. Pearson correlation was used to assess the association between variables. Results: In obese subjects of both sexes, circulating IL-6, clusterin and irisin levels were significantly elevated and positively correlated with HOMA-IR. Obese males showed significantly higher HOMA-IR, IL-6, clusterin and irisin levels than obese females. Conclusion: Obesity in both sexes, especially in males was associated with high levels of IL-6, clusterin and irisin and worsened the metabolic pattern. Circulating IL-6, clusterin and irisin may represent possible therapeutic targets for insulin resistance in obese subjects.