Composition of Microbiota in Transient and Mature Human Milk: Significant Changes in Large for Gestational Age Group.

The composition of the human milk (HM) microbiota and, consequently, the microorganisms that are passed on to the infant through breastfeeding, can be influenced by various factors such as the mother's health and diet, gestational age, delivery mode, lactation stage, method of infant feeding, and geographical location. The aim of the Human Milk-Gest Study was to compare the microbiota of transient (postpartum 7-15 days) and mature HM (postpartum 45-90 days) of 44 mothers, and to investigate any potential changes associated with preterm birth, mode of delivery, and birth weight in relation to gestational age. The data were classified into five study groups: normal spontaneous delivery-term (NS-T) newborns, cesarean delivery-term (CS-T) newborns, preterm (PT) newborns (with a gestational age of less than 37 weeks), small for gestational age (SGA) newborns, and large for gestational age (LGA) newborns. An analysis of differential abundance was conducted using ANCOM-BC to compare the microbial genera between transient and mature HM samples as well as between other study groups. A significant difference was detected between HM samples at different sampling times and between the study groups (p < 0.01). In transient HM samples, Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group compared to the NS-T, CS-T, PT, and SGA groups. In mature HM samples, Burkholderiaceae_uc, Ralstonia, Pelomonas, and Klebsiella were significantly dominant in the LGA group compared to the NS-T, CS-T, and PT groups, while Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group compared to the SGA group. Differences were also detected between the transient and mature HM samples in the CS-T, PT, SGA, and LGA groups, but no differences occurred in the NS-T groups. In conclusion, we showed that Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group in transient HM and continued in mature HM. The body mass index (BMI) of the mothers in the LGA group was not >30 at conception, however, the maternal BMI at birth and maternal weight gain during pregnancy were higher than in the other groups. The nutritional composition of HM is specifically designed to meet infant nutritional requirements during early life. Evaluating the effects of HM microbiota on infant microbiota composition and short- and long-term health effects in larger studies would be useful.

The relationship of retinopathy of prematurity with brain-derivated neurotrophic factor, vascular endotelial growth factor-A, endothelial PAD domain protein 1 and nitric oxide synthase 3 gene polymorphisms.

BACKGROUND: In addition to risk factors such as low birth weight and uncontrolled oxygen therapy, genetic predisposition is also thought to play a role in the development of retinopathy of prematurity (ROP). In our study, we aimed to analyze single-nucleotide polymorphisms (SNPs) in VEGFA, EPAS1, BDNF and NOS3 genes in infants who develop ROP. MATERIALS AND METHODS: Seventy-five mild-moderate and 73 severe ROP cases were included in this study. Eleven different SNPs regions that located in VEGFA, EPAS1, BDNF and NOS3 genes were analysed by SnapShot technique and compared between two groups by the multiple logistic regression analysis. RESULTS: Statistically significant results were obtained in 8 of the 11 SNPs. It was observed that the excess of mutant alleles in four (VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744) of these regions increased ROP severity and treatment requirement (p < .001, p < .001, p = .022, p = .004, respectively) while the excess of mutant alleles in the other four regions (VEGFA rs833061, BDNF rs7929344, EPAS1 rs1867785 and rs1868085) showed that ROP severtiy was milder and eliminated the need for treatment (p < .001, p = .019, p = .017, p = .017, respectively). CONCLUSIONS: Considering the results of our study, it was seen that besides the known environmental and demographic factors in ROP pathogenesis, genetic predisposition also had an effect on the clinic and course of ROP. Polymorphisms of VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744 were found to be associated with severe ROP. More studies involving different populations cases are needed to confirm these findings and enlighten the etiology of ROP.

Human Milk Virome Analysis: Changing Pattern Regarding Mode of Delivery, Birth Weight, and Lactational Stage.

The human milk (HM) microbiota is a significant source of microbes that colonize the infant gut early in life. The aim of this study was to compare transient and mature HM virome compositions, and also possible changes related to the mode of delivery, gestational age, and weight for gestational age. Overall, in the 81 samples analyzed in this study, reads matching bacteriophages accounted for 79.5% (mainly Podoviridae, Myoviridae, and Siphoviridae) of the reads, far more abundant than those classified as eukaryotic viruses (20.5%, mainly Herpesviridae). In the whole study group of transient human milk, the most abundant families were Podoviridae and Myoviridae. In mature human milk, Podoviridae decreased, and Siphoviridae became the most abundant family. Bacteriophages were predominant in transient HM samples (98.4% in the normal spontaneous vaginal delivery group, 92.1% in the premature group, 89.9% in the C-section group, and 68.3% in the large for gestational age group), except in the small for gestational age group (only ~45% bacteriophages in transient HM samples). Bacteriophages were also predominant in mature HM; however, they were lower in mature HM than in transient HM (71.7% in the normal spontaneous vaginal delivery group, 60.8% in the C-section group, 56% in the premature group, and 80.6% in the large for gestational age group). Bacteriophages still represented 45% of mature HM in the small for gestational age group. In the transient HM of the normal spontaneous vaginal delivery group, the most abundant family was Podoviridae; however, in mature HM, Podoviridae became less prominent than Siphoviridae. Myoviridae was predominant in both transient and mature HM in the premature group (all C-section), and Podoviridae was predominant in transient HM, while Siphoviridae and Herpesviridae were predominant in mature HM. In the small for gestational age group, the most abundant taxa in transient HM were the family Herpesviridae and a species of the genus Roseolovirus. Bacteriophages constituted the major component of the HM virome, and we showed changes regarding the lactation period, preterm birth, delivery mode, and birth weight. Early in life, the HM virome may influence the composition of an infant's gut microbiome, which could have short- and long-term health implications. Further longitudinal mother-newborn pair studies are required to understand the effects of these variations on the composition of the HM and the infant gut virome.

A single dose of aminophylline administration during therapeutic hypothermia; does it make a difference in glomerular filtration rate?

Aminophylline has been demonstrated to be effective in improving renal functions of the infants suffering from acute kidney injury (AKI) due to perinatal asphyxia. We aimed to evaluate the effect of a single-dose aminophylline on estimated glomerular filtration rate (eGFR), urine output (UO), and incidence and severity of AKI according to the pediatric-modified RIFLE and neonatal RIFLE criteria in newborns with perinatal asphyxia under therapeutic hypothermia. This was a single-center, retrospective cohort study including newborns (gestational age ≥36 weeks) who underwent therapeutic hypothermia due to hypoxic ischemic encephalopathy between 2016 and 2019. Demographic and clinical data were obtained from electronic medical records and patient files. Two patient groups were established: aminophylline group and control group which were only under therapeutic hypothermia. Twenty-one newborns were in the aminophylline group and 13 newborns were in the control group. Our study revealed that on the third day of life (DOL), eGFR was significantly higher in the control group (p=0.025), but UO was significantly higher in the aminophylline group (p=0.021). In the aminophylline group, eGFR on the first DOL was higher than the value on the second DOL (p=0.017) while UO was higher on the second and third DOL compared to the first DOL (1-2 DOL p=0.006, and 1-3 DOL p=0.004). However, in the control group, there was no statistically significant difference in UO over the four DOL. Both groups were similar in the presence, severity, and outcome of AKI.Conclusion: This study demonstrated that aminophylline increases UO even in the infants under therapeutic hypothermia. However, the eGFR did not significantly increase in the aminophylline group. Understanding how therapeutic hypothermia affects pharmacokinetics may help us improve our results in future studies. What is known: • Therapeutic hypothermia (TH) reduces the incidence of acute kidney injury in asphyxiated newborns. • Aminophylline is effective in improving renal functions in asphyxiated newborns. What is new: • This is the first study evaluating the effect of a single dose of aminophylline on renal functions in newborns under TH. • A single dose of aminophylline administration in newborns under TH was associated with increased urine output especially on the third day of life. However, no significant increase was detected in glomerular filtration rate associated with aminophylline administration.

Cerebral sinovenous thrombosis in children: clinical presentation, locations, and acquired and inherited prothrombotic risk factors.

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) in children is a rare and life-threatening cerebrovascular disease. Hence, we evaluated its clinical presentations, inherited and acquired prothrombotic risk factors along with the accompanying diseases, the thrombosis locations as well as the outcomes of anticoagulant therapy in children with CSVT. METHODS: The medical records of pediatric CSVT patients treated between January 2011 and September 2018 were analyzed retrospectively. RESULTS: The study included 29 children, 15 boys (51.7%) and 14 girls (48.3%), with the median age being 11 years (range:3 days-17 years). The most commonly presented complaint in neonates was seizures and in the non-neonatal age groups was a headache. Also, at least one acquired and/or inherited thrombophilic risk factor was identified in 89.7% of the patients. The most commonly acquired prothrombotic risk factors along with the accompanying diseases included infections, central venous catheter, and dehydration, while the most commonly inherited thrombophilic risk factors included heterozygous factor-V Leiden mutation and elevated lipoprotein (a). The most common thrombosis location was found to be the transverse sinus. Also, none of the patients died due to the thrombotic episode. Complications included epilepsy in five patients, hydrocephalus in one patient, and intracranial hypertension in another patient. CONCLUSIONS: Clinicians need to be well aware of the inherited and acquired prothrombotic risk factors in CSVT. It should also be kept in mind that at-risk patients may also present with nonspecific signs and symptoms with no apparent neurological manifestation. The risk of acute complications and long-term sequelae can be substantially reduced if diagnosed early and initiated with appropriate treatment at the early stages.

Evaluation of Total Antioxidant Capacity and Total Oxidant Status of Preterm and Term Breast Milk during the Course of Lactation and within a Nursing Session.

OBJECTIVE: Breast milk (BM) contains antioxidant molecules which may offer protection against oxidative stress (OS). We aim to investigate oxidant-antioxidant balance in preterm BM during the course of lactation and within a nursing session. STUDY DESIGN: Total antioxidant capacity (TAC) and total oxidant status (TOS) were measured in colostrum, transitional, and mature BM samples of preterm infants born earlier than 34th week of pregnancy and healthy term infants. Oxidative stress index (OSI) was calculated. Foremilk and hindmilk samples were collected separately. RESULTS: In colostrum and transitional milk, TAC (p < 0.001 and p = 0.001, respectively) and TOS (p = 0.005 and p < 0.001, respectively) were lower in preterm BM compared with term BM. OSI was also lower in preterm BM, but it was statistically significant only in transitional milk (p < 0.001). TAC was highest in colostrum and decreased through the course of lactation. However, the decrease in TAC was not statistically significant in preterm BM. Lowest values of TOS and OSI were observed in colostrum. In transitional term BM, hindmilk had a better oxidant-antioxidant profile as indicated by lower TOS and OSI. CONCLUSION: Oxidant-antioxidant balance is preserved in BM in every stage of lactation. Preterm BM has lower OSI which may offer benefits to preterm newborn against OS.

The Relationship of Breastfeeding Patterns in the Neonatal Intensive Care Unit to Maternal Symptoms of Anxiety and Depression.

Background: The studies related to psychiatric disorders have demonstrated high frequency of maternal stress, anxiety, and postpartum depression in mothers who have infants in neonatal intensive care unit (NICU). It is well known that maternal anxiety and depression adversely affect breastfeeding. The research aims to examine the association between the anxiety and depressive symptom severity of NICU mothers and feeding type (exclusively breastfed [EBF] or mixed fed [MF]) of their infants within first week of life in NICU. Methods: Data were collected from 93 mothers and 105 infants in a single-center, prospective, cross-sectional, descriptive study. The state-trait anxiety and depressive symptom severity of NICU mothers were evaluated using the Spielberger State-Trait Anxiety Inventory (STAI, including Spielberger State-Trait Anxiety Inventory-State [STAI-S], Spielberger State-Trait Anxiety Inventory-Trait [STAI-T]), and Edinburgh Postnatal Depression Scale (EPDS). Results: Breastfeeding exclusivity in NICU infants was significantly related to gestational age, birth weight, prenatal steroid, and assisted reproductive technology (ART; p = 0.022, 0.041, 0.028, 0.017, respectively). The comparison of STAI-S, STAI-T, and EPDS scores of NICU mothers between EBF and MF groups revealed that STAI-T score was significantly high in EBF group than that in the MF group (p = 0.019). Logistic regression analyses showed that a 1-unit increase in STAI-T score in NICU mothers was significantly associated with a 5.7% increase in the odds of breastfeeding exclusivity within first week in postpartum period (p = 0.033; odds ratio = 1.057, 95% confidence interval = 1.004-1.113). Conclusions: Contrary to estimates, clinically significant state and trait anxiety symptoms and depressive symptoms of NICU mothers do not affect breastfeeding exclusivity negatively within first week of life in NICU. Preterm infants under 32 gestational weeks and infants born with ART have a tendency to being EBF.

A Turkish patient with novel AHCY variants and presumed diagnosis of S-adenosylhomocysteine hydrolase deficiency.

S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive neurometabolic disorder affecting the muscles, liver, and nervous system. The disease occurs by pathogenic variants of AHCY gene encoding S-adenosylhomocysteine hydrolase (AHCY) enzyme. This article reports a patient with presumed AHCY deficiency who was diagnosed by whole exome sequencing due to compound heterozygosity of novel p.T57I (c.170C>T) and p.V217M (c.649G>A) variants of AHCY gene. The patient had diffuse edema, coagulopathy, central nervous system abnormalities, and hypotonia. She died in 3 months due to cardiovascular collapse. Clinical findings of the present case were compatible with previously reported AHCY deficiency patients and the novel variants we found are considered to be the cause of the symptoms. This article also compiles the previous reports and expands clinical spectrum of AHCY deficiency by adding new features.

Role of Oxidative Stress in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Objectives: To investigate the role of oxidative stress on pseudoexfoliation formation and progression from pseudoexfoliation syndrome (XFS) to pseudoexfoliation glaucoma (XFG). Materials and Methods: This study investigated oxidative stress biomarkers in blood samples from 58 patients with XFG, 47 patients with XFS, and 134 healthy age- and sex-matched controls. Results: The highest serum malondialdehyde (MDA) levels were measured in XFG patients (p<0.001), and MDA level was higher in XFS patients than controls (p<0.001). Superoxide dismutase (SOD) and catalase (CAT) enzyme activities were significantly lower in XFS and XFG patients than in the control group, whereas a significant increase was observed in glutathione (GSH) levels (p<0.001 for all). However, levels of these three biomarkers did not differ significantly between XFS and XFG patients (p=0.188, p=0.185, and p=0.733, respectively). Nitric oxide (NO) concentration was significantly lower in XFG patients compared to XFS patients and controls (p<0.001) but did not differ between XFS patients and controls (p=0.476). Conclusion: Elevated MDA levels suggest that lipid peroxidation is important in XFS and XFG development and progression from XFS to XFG. In addition, reduction in SOD and CAT enzyme activities is considered a deficiency in the enzymatic antioxidant protection system. Furthermore, GSH values may be evaluated as a compensatory response to oxidative stress in XFS and XFG. Alterations in NO indicate the role of a vascular regulatory factor in the progression from XFS to glaucoma.

Propolis Protects Endotoxin Induced Acute Lung and Liver Inflammation Through Attenuating Inflammatory Responses and Oxidative Stress.

Propolis is a natural bee product, and it has many effects, including antioxidant, anti-inflammatory, antihepatotoxic, and anticancer activity. In this study, we aimed to explore the potential in vivo anti-inflammatory, antioxidant, and antiapoptotic properties of propolis extract on lipopolysaccharide (LPS)-induced inflammation in rats. Forty-two, 3- to 4-month-old male Sprague Dawley rats were used in six groups. LPS (1 mg/kg) was administered intraperitoneally to rats in inflammation, inflammation + propolis30, and inflammation+propolis90 groups. Thirty milligram/kilogram and 90 mg/kg of propolis were given orally 24 h after LPS injection. After the determination of the inflammation in lung and liver tissues by 18F-fluoro-deoxy-d-glucose-positron emission tomography (18FDG-PET), samples were collected. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), nitric oxide (NO), and DNA fragmentation were determined. The decrease of MDA levels in inflammation + propolis30 and inflammation + propolis90 groups was determined compared to the inflammation group in lung and liver tissues. The increase of SOD% inhibition in inflammation + propolis90 group was determined in liver, lung, and hemolysate compared to the inflammation group. Increased CAT activities in inflammation + propolis30 and inflammation + propolis90 groups were observed in liver tissue and hemolysate compared to inflammation group. In lung tissue, NO levels were lower in inflammation group compared to the control group, but DNA fragmentation levels were higher. 18F-FDG uptake of tissues in inflammation + propolis30 and inflammation + propolis90 groups was decreased compared to the inflammation group. In conclusion, the data of this study indicate that the propolis application may serve as a potential approach for treating inflammatory diseases through the effect of reducing inflammation and free oxygen radical production.

Posttreatment Effects of Olea Europaea L. Leaf Extract on Carbon Tetrachloride-Induced Liver Injury and Oxidative Stress in Rats.

The aim of this study is to examine the therapeutic effects of Olea europaea L. leaf extract on carbon tetrachloride (CCl4)-induced liver damage in rats. In the experiments, 3- to 4-month-old 28 male Sprague-Dawley rats were divided into four groups: control, O. europaea leaf extract, CCl4, and curative. The CCl4 and curative groups received CCl4 (0.2 mL/kg) intraperitoneally for 10 days to form hepatic injury. O. europaea (80 mg/kg) leaf extract was given orally to the curative group dissolved in distilled water the following 14 days. Hepatic and antioxidant enzyme levels, p53, caspase 3, lipid peroxidation marker malondialdehyde (MDA), and also DNA fragmentation levels were determined to establish oxidative stress in hepatic cell damage and its consequences. After formation of liver damage, oral administration of the O. europaea significantly reduced CCl4-induced elevations of serum alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase levels (P < .001), MDA levels of both blood (P < .001) and liver tissues (P < .001), DNA fragmentation (P < .001), p53 (P < .001), and caspase 3 (P < .001) levels of liver tissues. Also this administration in curative group significantly increased CCl4-induced reductions of superoxide dismutase (SOD) (P < .001) and catalase (CAT) (P < .001) activity of blood samples and decreased SOD (P < .001) and CAT (P < .05) activity observed in liver tissue curative groups compared with CCl4 curative group. In CCl4 group, liver tissue samples exhibited remarkable damage because of CCl4 and reduction of these damages were observed in the curative group. Our results showed that O. europaea leaf extract was effective in reducing hepatic damage caused by CCl4 by reducing lipid peroxidation, regulating antioxidant enzymes, and minimizing DNA damage.

Neonatal hemodynamics and management of hypotension in newborns.

Hemodynamic instability is frequent in high-risk infants admitted to neonatal intensive care units. However, monitoring and treatment strategies of those conditions might show variations among the units. Different factors can compromise hemodynamic status in preterm/ term infants. Treatment options mostly include volume replacement, inotropes and/or vasopressors (dopamine, dobutamine, epinephrine and milrinone) and hydrocortisone. In general, these treatments are driven by predetermined protocols, which are not patient-based. According to the current knowledge, a physiology-driven approach that takes the individual characteristics of the newborn into consideration is accepted to be more suitable. In neonatal hemodynamics, important determinants are cardiac output, systemic vascular resistance, blood pressure, regional tissue perfusion and oxygenation. The novel technological methods, "targeted neonatal echocardiography" and "near-infrared spectroscopy" can help to delineate the underlying pathophysiology better, when added to the clinical assessment. In this review, strategies for the assessment of neonatal hemodynamics, as well as etiology, monitoring, and treatment of hemodynamic instability in preterm and term infants are presented.

Neonatal effects of thyroid diseases in pregnancy and approach to the infant with increased TSH: Turkish Neonatal and Pediatric Endocrinology and Diabetes Societies consensus report.

Thyroid functions in the fetus and newborn carry importance in terms of the baby's health and development of the central nervous system. Maternaliodine deficiency, exposure to iodine, thyroid diseases (Hashimoto thyroiditis, Graves') and drugs used by the mother affect thyroid functions in the fetus. Reflections of these effects are observed immediately after delivery. Investigation of the mother in terms of thyroid diseases during pregnancy, recognition and appropriate assessment of the required conditions, screening of all newborns in the first days of life in terms of congenital hypothyroidism, timely and appropriate evaluation of the screening results, early diagnosis and appropriate treatment of cases of congenital hypothyroidism, assessment and management of cases of transient thyroid hormone disorders and close monitoring of the thyroid functions and development of patients in whom treatment has been initiated with a diagnosis of hypothyroidism are crucial in terms of developmental outcomes of the babies who have thyroid function disorders or hypothyroidism. This guideline was written with the objective of guiding pediatricians, neonatologists and pediatric endocrinologists in the issue of assessment, diagnosis and management of thyroid function disorders and thyroid diseases concerning the fetus and baby during gestation and neonatal period.

The Anti-Inflammatory and Antioxidant Effects of Salvia officinalis on Lipopolysaccharide-Induced Inflammation in Rats.

Salvia officinalis, which has a high phenolic acid and flavonoid content, is a powerful antioxidant and anti-inflammatory herb. Inflammation plays an important role in the pathophysiology of many diseases and could cause damage by means of oxidative stress. The aim of this study was to investigate the anti-inflammatory and antioxidant activity of S. officinalis formed lipopolysaccharide (LPS)-induced experimental inflammation model. Four- to five-month-old 42 female Wistar albino rats were divided into six groups. Three groups were administered intraperitoneally 1 mg/kg LPS. Twenty-four hours after injection of LPS, 10 and 30 mg/kg S. officinalis extract were given orally to treatment groups. Pulmonary and hepatic 18F-fluoro-deoxy-D-glucose (18F-FDG) uptake was calculated to determine the status of inflammation by 18F-fluoro-deoxy-D-glucose-positron emission tomography (18FDG-PET) scan. Antioxidant enzyme activities and nitric oxide (NO) and malondialdehyde (MDA) levels were determined. Nuclear factor-kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) levels were also detected in serum. As a result, lung and liver 18F-FDG uptake was found to be higher in the inflammation group than control group. MDA levels in erythrocyte and all tissue samples (liver, lung, and kidney) were found to be significantly higher compared to treatment groups. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities of the inflammation group in the liver, lung, kidney tissues, and erythrocyte SOD and CAT activities were determined to significantly lower than groups treated with S. officinalis. Increased NO, NF-κB, and TNF-α levels were found in the inflammation group. S. officinalis has been observed to have useful effects on LPS-induced inflammation and oxidative stress in rats.

A case of Donohue syndrome "Leprechaunism" with a novel mutation in the insulin receptor gene.

Donohue syndrome (Leprechaunism) is characterized by severe insulin resistance, hyperinsulinemia, postprandial hyperglycemia, preprandial hypoglycemia, intrauterine and postnatal growth retardation, dysmorphic findings, and clinical and laboratory findings of hyperandrogenemia due to homozygous or compound heterozygous inactivating mutations in the insulin receptor gene. A female newborn presented with lack of subcutaneous fat tissue, bilateral simian creases, hypertrichosis, especially on her face, gingival hypertrophy, cliteromegaly, and prominent nipples. Her laboratory tests revealed hyperandrogenism, postprandial hyperglycemia and preprandial hypoglycemia, and very high concurrent insulin levels. She was diagnosed as having Donohue syndrome. Metformin and continuous nasogastric feeding were administrated. During follow-up, relatively good glycemic control was obtained. However, severe hypertrophic obstructive cardiomyopathy and severe malnutrition developed. She died aged 75 days of severe heart failure and pneumonia. Her insulin receptors gene analysis revealed a compound heterozygous mutation. One of these mutations was a p.R813 (c.2437C>T) mutation, which was defined previously and shown also in her father, the other mutation was a novel p.777-790delVAAFPNTSSTSVPT mutation, also shown in her mother. The parents were heterozygous for these mutations.

The hepatocurative effects of Cynara scolymus L. leaf extract on carbon tetrachloride-induced oxidative stress and hepatic injury in rats.

Cynara scolymus is a pharmacologically important medicinal plant containing phenolic acids and flavonoids. Experimental studies indicate antioxidant and hepatoprotective effects of C. scolymus but there have been no studies about therapeutic effects of liver diseases yet. In the present study, hepatocurative effects of C. scolymus leaf extract on carbon tetrachloride (CCl4)-induced oxidative stress and hepatic injury in rats were investigated by serum hepatic enzyme levels, oxidative stress indicator (malondialdehyde-MDA), endogenous antioxidants, DNA fragmentation, p53, caspase 3 and histopathology. Animals were divided into six groups: control, olive oil, CCl4, C. scolymus leaf extract, recovery and curative. CCl4 was administered at a dose of 0.2 mL/kg twice daily on CCl4, recovery and curative groups. Cynara scolymus extract was given orally for 2 weeks at a dose of 1.5 g/kg after CCl4 application on the curative group. Significant decrease of serum alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) levels were determined in the curative group. MDA levels were significantly lower in the curative group. Significant increase of superoxide dismutase (SOD) and catalase (CAT) activity in the curative group was determined. In the curative group, C. scolymus leaf extract application caused the DNA % fragmentation, p53 and caspase 3 levels of liver tissues towards the normal range. Our results indicated that C. scolymus leaf extract has hepatocurative effects of on CCl4-induced oxidative stress and hepatic injury by reducing lipid peroxidation, providing affected antioxidant systems towards the normal range. It also had positive effects on the pathway of the regulatory mechanism allowing repair of DNA damage on CCl4-induced hepatotoxicity.

The Diagnostic Value of Troponin T Level in the Determination of Cardiac Damage in Perinatal Asphyxia Newborns.

Perinatal asphyxia is a clinical condition which results from oxygen deprivation of the fetus or newborn and the breakdown of perfusion in various organs. The aim of this study was to evaluate and compare troponin T levels over time as a marker of cardiac injury in cases of perinatal asphyxia and healthy newborns. The study included a total of 30 newborns diagnosed with perinatal asphyxia with a gestational age of 32-41 weeks, based on the last menstruation date, and 30 healthy newborns with a gestational age of 34-40 weeks, as the control group. Levels of troponin T and creatinin kinase MB were recorded for all participants. No difference was determined between the groups in terms of gestational age, manner of birth, electrocardiographic findings, and PaO2 and PaCO2 values. The umbilical artery pH levels and bicarbonate levels in the study group were found to be statistically lower than those in the control group (p < 0.001). The troponin T and creatinin kinase MB levels in the patients in the study group were higher than those within the control group, at all times. The periods when specificity and sensitivity were highest together for troponin T were the 12th and 24th h. Specificity for troponin T reached the highest value at the 24th h and sensitivity reached the highest value in the cord blood. A positive correlation was found between the troponin T and creatinin kinase MB values at the 6th and 12th h. However, no correlation could be found in the blood between the serum troponin T and creatinin kinase MB levels at the 3rd and 24th h. The troponin T level is a useful test for showing cardiac damage in hypoxic patients in the neonatal period. The sensitivity and specificity of cardiac specific troponin T levels in detecting cardiac damage are much higher according to telecardiography and electrocardiography, while the implementation of the method is simple.

Effects of S-allyl cysteine on lung and liver tissue in a rat model of lipopolysaccharide-induced sepsis.

Sepsis is characterized by a severe production of reactive oxygen species (ROS) and other radical species with consequent oxidative stress. S-allyl cysteine (SAC) is a water-soluble organosulfur component present in garlic which is a potent antioxidant and free radical scavenger. In the present study, the purpose was to explore the anti-inflammatory, antioxidant, and anti-apoptotic actions of SAC on lipopolysaccharide (LPS)-induced sepsis in rats. Thirty-two male Wistar rats were separated into 4 groups. These were control, SAC control, sepsis, and sepsis + SAC-induced groups. Sepsis was induced by administration of LPS (5 mg/kg) into 2 groups. SAC (50 mg/kg) was given orally to SAC control and SAC treatment groups per 12 h during 2 days after intraperitoneal LPS injection. Serum AST, ALT, ALP, and hsCRP levels and liver and lung MPO, NO, and DNA fragmentation levels were evaluated. In sepsis group, elevated levels of ALT, AST, ALP, and hsCRP were observed. The abnormal increases were decreased in sepsis + SAC group compared to sepsis group. In lung tissue, MPO and NO levels were increased in sepsis group compared to the control group. MPO activity and NO levels were decreased by SAC application in sepsis + SAC group compared with sepsis group. In liver tissue, DNA fragmentation was significantly higher in sepsis group than that in the control group. In contrast, a decreased level of DNA fragmentation was noted in sepsis + SAC group when compared with the sepsis group. In conclusion, SAC ameliorates LPS-induced indicators of liver damage and suppresses the discharge of NO and MPO in lung tissue via its antioxidant properties.

Apoptotic effects of dipyrido [3,2-a:2',3'-c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats.

We evaluated the effects of dipyrido [3,2-a:2',3'-c] phenazine (dppz) Au(III) complex ([Au(dppz)Cl2]Cl) on apoptosis during chemically induced hepatocellular carcinoma. 48 male Spraque-Dawley rats were divided into six groups; group I (control), group II [Dimethyl sulfoxide (DMSO)], group III ([Au(dppz)Cl2]Cl), group IV [diethylnitrosamine + Phenobabital (DEN + PB)], group V (DEN + PB + [Au(dppz)Cl2]Cl (2nd week)), and group VI (DEN + PB + [Au(dppz)Cl2]Cl (7th week). The rats in groups IV through VI were administrated with DEN in a single dose of intraperitoneal 175 mg/kg. After 2 weeks of DEN administration, these groups of rats were given daily PB in a dose of 500 ppm. In group V, after two weeks of DEN administration, [Au(dppz)Cl2]Cl complex (2 mg/kg) was given once a week by intraperitoneal injection. In the group VI, the rats were given a dose of 2 mg/kg [Au(dppz)Cl2]Cl complex once a week, 7 weeks after DEN administration. At the end of the study, blood and tissue samples were collected from the rats to determine levels of serum AST, ALT, and LDH, and caspase 3, p53, Bax, Bcl-2 and DNA fragmentation in liver. AST, ALT, LDH, and Bcl-2 levels were higher in group IV, compared to group I, but caspase 3 and p53 levels were lower. In group V, caspase 3, p53, Bax, and DNA fragmentation levels were higher than those of group IV. Caspase 3 and p53 levels increased in group VI compared with group IV. In conclusion, [Au(dppz)Cl2]Cl complex induced apoptosis by elevating levels of caspase 3, p53, Bax, and DNA fragmentation.

Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: 18FDG-PET imaging of inflammation.

Inflammation has an important role in many diseases such as cystic fibrosis, allergies and cancer. The free radicals produced during inflammation, can induce gene mutations and posttranslational modifications of cancer related proteins. Nigella sativa L. (N. sativa) is herbaceous plant and commonly used as a natural food. It has many pharmacological effects including antibacterial, antifungal, antitumor, analgesic, antipyretic activity. The aim of this study was to investigate the anti-inflammatuar and anti-oxidant activity of N. sativa in acute inflammation. Thus we used the experimental lipopolysaccharides (LPS)-induced model. Intraperitoneal LPS 1 mg/kg was administered to groups. N. sativa (500 mg/kg) and essential oil (5 ml/kg) were given orally to treatment groups, after 24-h of intraperitoneal LPS-injection. To determine the lung inflammation, 18F-fluoro-deoxy-D-glucose (0.8 ml/kg) was administrated under the anesthesia before the 1 h of PET-scanning. After the FDG-PET, samples were collected. Lung and liver 18F-FDG-uptake was calculated. Serum AST, ALT, LDH and hcCRP levels were determined and liver, lung and erythrocyte SOD, MDA and CAT levels were measured. Liver and lung NO and DNA fragmentation levels were determined. MDA levels were decreased in treated inflammation groups whereas increased in untreated inflammation group. SOD and CAT activities in untreated inflammation group were significantly lower. According to the control group, increased AST and ALT levels were found in untreated inflammation group. 18F-FDG uptake of inflammation groups were increased when compare the control group. We found increased 18F-FDG uptake, DNA fragmentation and NO levels in LPS-induced inflammation groups. We conclude that, in LPS-induced inflammation, N. sativa have therapeutic and anti-oxidant effects.