Metformin as adjuvant therapy in obese knee osteoarthritis patients.

AIMS: This study aimed at investigating the efficacy of metformin as adjuvant therapy for obese knee osteoarthritis (OA) patients, considering its anti-inflammatory and cartilage-protective effects. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled study, 50 obese knee OA patients were assigned randomly to two groups, the metformin group (n = 25) which was treated with metformin 500 mg orally BID plus celecoxib 200 mg orally once daily, and the placebo group (n = 25) which was treated with placebo tablets BID plus celecoxib 200 mg orally once daily for 12 weeks. Cartilage Oligomeric Matrix Protein (COMP), C-terminal cross-linked telopeptide of type I collagen (CTX-1), and Interleukin 1-beta (IL-1ß) serum levels were measured, while Western Ontario and McMaster Universities Arthritis Index (WOMAC) score assessed knee pain, stiffness, and physical function at baseline and after 12 weeks. RESULTS: Following a 12-week treatment, the metformin group exhibited significantly reduced levels of COMP, CTX-1, and IL-1ß in the serum compared to the placebo group (p = 0.0081, p = 0.0106, and p = 0.0223, respectively). Furthermore, metformin group produced significant improvements in WOMAC total scale (p < 0.0001), specifically in knee pain, stiffness, and physical function compared to placebo group (p < 0.0001, p < 0.0001, and p < 0.0001, respectively). CONCLUSION: Metformin as an adjuvant therapy in obese knee OA patients may have beneficial effects on cartilage degradation and inflammation, as evidenced by the significant decreases in serum COMP, CTX-1, and IL-1ß levels. Additionally, metformin may improve clinical outcomes, as shown by the significant improvements in WOMAC scores. GOV ID: NCT05638893/Registered December 6, 2022 - Retrospectively.

L-carnitine decreases myocardial injury in children undergoing open-heart surgery: A randomized controlled trial.

Myocardial injury in open-heart surgery is related to several factors including ischemia-reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\kg\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group.   Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.   Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients. What is Known: • Myocardial injury in open-heart surgery is related to several factors including ischemia-reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. • L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery. What is New: • L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group. • L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.

Lactoferrin for iron-deficiency anemia in children with inflammatory bowel disease: a clinical trial.

BACKGROUND: Iron-deficiency anemia (IDA) is common in children with inflammatory bowel disease (IBD); however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. We compared the effect of lactoferrin versus oral ferrous sulfate for the treatment of IDA in children with IBD. METHODS: Ninety-two IBD children with IDA were included but only 80 children completed the study and they were randomized into two groups: ferrous sulfate group (n = 40) who received ferrous sulfate 6 mg/kg/day for 3 months and lactoferrin group (n = 40) who received lactoferrin 100 mg/day for 3 months. Complete blood count, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TS), serum ferritin, interleukin-6 (IL-6), and hepcidin 25 were measured before and after the treatment. RESULTS: Hemoglobin (Hb), mean corpuscular volume, serum iron, TS, and serum ferritin significantly increased, while TIBC decreased significantly after the administration of either ferrous sulfate or lactoferrin compared to their baseline data. In addition, lactoferrin significantly increased Hb, serum iron, TS, and serum ferritin compared to ferrous sulfate. Moreover, lactoferrin significantly decreased IL-6 and hepcidin levels. CONCLUSION: Lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA. CLINICAL TRIAL REGISTRATION: The study was registered at www.pactr.org (PACTR202002763901803). IMPACT: Iron-deficiency anemia (IDA) in children with inflammatory bowel disease (IBD) is treated with oral iron therapy; however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. To the best of our knowledge, our study was the first in pediatrics that compared the effect of lactoferrin versus oral ferrous sulfate as an iron supplement for the treatment of IDA in children with IBD. We found that lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA.

Insulin resistance, leptin and adiponectin in lean and hypothyroid children and adolescents with obesity.

BACKGROUND: Obesity usually complicates hypothyroidism. Adipokines like leptin and adiponectin secreted by adipose tissue modulate insulin resistance (IR), appetite, and obesity. The association between adipokines, IR, and thyroid hormone has not been sufficiently studied in children. We investigated leptin and adiponectin as well as IR and their association with thyroid hormone in both lean and hypothyroid children and adolescents with obesity. METHODS: The study included 30 lean hypothyroid, 30 hypothyroid children and adolescents with obesity, and 30 healthy lean children as the control group. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), fasting blood glucose, fasting insulin, homeostatic model assessment method of insulin resistance (HOMA-IR), leptin, and adiponectin levels were estimated in all participants. RESULTS: Fasting insulin, HOMA-IR, and leptin levels were significantly elevated in hypothyroid children compared to the control group; more in hypothyroid children with obesity. In contrast, adiponectin levels were significantly lower in the hypothyroid children with obesity compared to the lean hypothyroid children and controls. HOMA-IR was positively correlated to TSH and BMI but inversely correlated with fT3 and fT4 in hypothyroid children. There was no correlation between IR and either leptin or adiponectin levels. Leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity. CONCLUSION: Insulin resistance and leptin levels are increased in hypothyroid children and adolescents; more in those with obesity. IR is not related to leptin and adiponectin levels, however, leptin and adiponectin levels correlate well with BMI in hypothyroid children and adolescents with obesity. IMPACT: Insulin resistance (IR) and leptin levels increase in hypothyroid children and adolescent; more with obesity. IR is not related to leptin and adiponectin levels, however leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity.

Omega 3 fatty acids can reduce early doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukemia.

OBJECTIVES: Omega 3 polyunsaturated fatty acids are dietary factors with several beneficial cardiovascular effects. This study aimed to assess the possible protective effect of omega 3 fatty acids on early doxorubicin-induced cardiac toxicity in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Sixty children of newly diagnosed ALL were randomized into two groups: group I (n = 30) who received omega 3 fatty acids 1000 mg/day for 6 months in addition to their usual protocol of chemotherapy including doxorubicin; and group II (n = 30) who received their usual doxorubicin protocol during the period from February 2020 till August 2021. Echocardiographic examinations were performed before and after the treatment. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), troponin I, creatine kinase MB (CK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured also before and after omega 3 treatment. RESULTS: After 6 months of omega 3 administration, group I had a significantly lower MDA level and a significantly higher glutathione and SOD levels than group II. Similarly, the levels of troponin I, CK-MB, and NT-proBNP were significantly high in group II, whereas they were unchanged in group I after treatment. Similarly, systolic function (presented with peak mitral annular systolic velocity and two-dimensional global longitudinal strain) of the heart was preserved in omega 3-treated patients, unlike the control group that showed significant impairment of left ventricular function after 6 months. CONCLUSION: Omega 3 fatty acids may decrease early cardiac injury and doxorubicin-induced cardiotoxicity in children with ALL.

Relationship between bone turnover markers and oxidative stress in children with type 1 diabetes mellitus.

BACKGROUND: Oxidative stress in children with type 1 DM (T1DM) may negatively affect the bone. METHODS: This study included 40 children with T1DM as the patient group and 40 healthy children of matched age and sex as the control group. Plasma alkaline phosphatase, procollagen type-1 amino-terminal propeptide (P1NP), and urinary deoxypyridinoline (DPD) were measured to assess bone turnover. Glutathione, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess oxidative stress. RESULTS: Patients with T1DM had a significantly lower P1NP level but a significantly higher urinary DPD level compared to the control group. Moreover, there were significantly lower glutathione and SOD levels with significantly higher MDA levels in patients with T1DM. We found a significant positive correlation between P1NP level and both glutathione and SOD levels but a significant negative correlation between P1NP and MDA in patients with T1DM. There was a significant negative correlation between DPD levels and both glutathione and SOD levels and a significant positive correlation between DPD and MDA. Moreover, glutathione was a significant predictor for both P1NP and DPD levels, while MDA was a significant predictor for P1NP levels. CONCLUSIONS: There is an association between oxidative stress and bone turnover markers in children with T1DM. IMPACT: Oxidative stress can negatively affect bone but the exact relationship between oxidative stress and bone turnover in T1DM has not been previously studied in pediatrics. For the best of our knowledge, our study was the first to assess the relationship between oxidative stress and bone turnover in children with T1DM. We revealed that increased oxidative stress in children and adolescents with T1DM may be involved in the impairment of bone turnover process, so treatment strategies toward better glycemic control and decreasing oxidative stress may be beneficial in preventing and treating diabetic bone disease in these children.

Osteocalcin and osteoprotegerin levels and their relationship with adipokines and proinflammatory cytokines in children with nonalcoholic fatty liver disease.

OBJECTIVES: To investigate the relationship between osteocalcin and osteoprotegerin as bone markers and inflammatory biomarkers such as adiponectin, leptin, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in children with nonalcoholic fatty liver disease (NAFLD). METHODS: This study included 40 obese children with NAFLD as the patient group and 40 healthy obese children of matched age, sex and BMI as the control group. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose, fasting insulin, Homeostatic model assessment method of insulin resistance (HOMA-IR), lipid profile, osteocalcin, osteoprotegerin, adiponectin, leptin, TNF-α, and IL-6 were measured in all participants. RESULTS: Children with NAFLD had a significant decrease in osteocalcin, osteoprotegerin and adiponectin level with a significant increase in TNF-α and IL-6 levels. We also found a significant positive correlation between osteocalcin level and adiponectin levels but a significant negative correlation of osteocalcin with each of leptin and TNF-α. However, there was a significant negative correlation between osteoprotegerin levels and both TNF-α and IL-6 levels. Moreover, adiponectin and TNF-α were significant predictors for osteocalcin, and IL-6 was a significant predictor for osteoprotegerin. CONCLUSION: Adiponectin, leptin, TNF-α, and IL-6 have potential association with the changes of osteocalcin and osteoprotegerin levels in children with NAFLD.

Effects of alpha lipoic acid as a supplement in obese children and adolescents.

OBJECTIVES: Obesity is significantly associated with inflammatory process and oxidative stress. Alpha lipoic acid (ALA) is a potent antioxidant that has been reported for reducing weight in animals and obese adults in several studies but no data are available in pediatrics. We investigated the possible beneficial role of ALA in obese children. PATIENTS AND METHODS: Eighty obese children and adolescents were randomized into two groups; the treatment group (n = 40) who received 300 mg of ALA twice daily for 3 months and the control group (n = 40) who received placebo for 3 months. Measurements of weight, body mass index (BMI), lipid profile, fasting blood glucose (FBG), malondialdhyde (MDA), tumor necrosis factor alpha (TNF-α), leptin and adiponectin were carried out before and 3 months after the treatment. RESULTS: ALA treatment group had a significant reduction of the weight, BMI, MDA, TNF-α, and leptin levels but a significant increase of adiponectin level (P < 0.05) compared to the control group. However, it had no effect on FBG or lipid profile (P > 0.05). CONCLUSION: ALA may be a promising supplement in the weight reduction in obese children and adolescents.

Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes.

BACKGROUND: Oxidative stress plays an important role in the development of diabetic cardiomyopathy. Alpha-lipoic acid (ALA) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction. AIM: We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular (LV) dysfunction in children and adolescents with asymptomatic type 1 diabetes (T1D). SUBJECTS AND METHODS: Thirty T1D patients (aged 10-14) were randomized to receive insulin treatment (n = 15) or insulin plus alpha-lipoic acid 300 mg twice daily (n = 15) for four months. Age and sex matched healthy controls (n = 15) were also included. Patients were evaluated with conventional 2-dimensional echocardiographic examination (2D), pulsed tissue Doppler (PTD), and 2-dimensional longitudinal strain echocardiography (2DS) before and after therapy. Glutathione, malondialdhyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), Fas ligand (Fas-L), matrix metalloproteinase 2 (MMP-2), and troponin-I were determined and correlated to echocardiographic parameters. RESULTS: Diabetic patients had significantly lower levels of glutathione and significantly higher MDA, NO, TNF-alpha, Fas-L, MMP-2, and troponin-I levels than control subjects. The expression of transforming growth factor beta (TGF-beta) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients. Significant correlations of mitral e'/a' ratio and left ventricular global peak systolic strain with glutathione, MDA, NO, TNF-alpha, and Fas-L were observed in diabetic patients. Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA, NO, TNF-alpha, Fas-L, MMP-2, troponin-I levels, and TGF-beta gene expression. Moreover, alpha-lipoic acid significantly increased mitral e'/a' ratio and left ventricular global peak systolic strain in diabetic patients. CONCLUSION: These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes.

The effect of ciprofloxacin and clarithromycin on sildenafil oral bioavailability in human volunteers.

Sildenafil is the first oral therapeutic agent for the management of male erectile dysfunction. Its oral bioavailability is only 40% due to extensive presystemic elimination, mainly by CYP3A4. This study examined the effect of coadministration of ciprofloxacin or clarithromycin, which inhibit CYP3A4, on the bioavailability and pharmacokinetics of sildenafil. Twelve healthy male volunteers received sildenafil alone or after pretreatment with the inhibitors in a balanced three-way crossover design. The pharmacokinetic analysis showed that ciprofloxacin coadministration with sildenafil significantly increased the AUC from 1407 +/- 380 to 2986 +/- 917 microg h/l (90% confidence interval 119%-159%) and the Cmax from 287 +/- 67 to 623 +/- 192 microg/l (90% confidence interval 127%-152%). Similarly, clarithromycin coadministration increased sildenafil AUC from 1407 +/- 380 to 3209 +/- 762 microg h/l (90% confidence interval 127%-161%) and Cmax from 287 +/- 67 to 694 +/- 259 microg/l (90% confidence interval 132%-157%). Ciprofloxacin coadministration and clarithromycin coadministration with sildenafil did not affect the rate of sildenafil absorption significantly. These results indicate that coadministration of ciprofloxacin and clarithromycin significantly increased sildenafil bioavailability which can be attributed to the inhibitory effect of ciprofloxacin and clarithromycin on CYP3A4. Dose adjustment of sildenafil is thus necessary when administered with such drugs.