Cardioprotective roles of aged garlic extract, grape seed proanthocyanidin, and hazelnut on doxorubicin-induced cardiotoxicity.

Doxorubicin (DXR) is a chemotherapeutic agent used effectively in the treatment of several childhood malignancies. During treatment, cardiotoxicity caused by cell damage due to the free oxygen radicals that are generated is a major limiting factor. This study was undertaken to determine whether DXR-induced cardiotoxicity could be prevented by natural foods with antioxidant properties such as aged garlic extract (AGEX), grape seed proanthocyanidin (PA), and hazelnut. Wistar albino male rats were assigned randomly to 9 groups each consisting of 15 rats. AGEX, PA, and hazelnut groups received these antioxidants in addition to their standard rat diet. They were also treated with cumulative intraperitoneal (i.p.) injections according to 2 different regimens: either a high-dose of 15 mg/kg DXR (3.75 mg/kg per week for 4 weeks) or a low-dose of 7.5 mg/kg DXR (1.875 mg/kg per week for 4 weeks). The control group received i.p. 0.9% saline. AGEX, PA, or hazelnut supplements were given orally to the groups for a 6-week period starting 1 week before the DXR treatment and ending 1 week after the treatment. One week after the last DXR injection, heart tissue samples were analyzed to determine malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and xanthine oxidase (XO) levels, and serum samples were taken for creatine kinase (CK). There were no significant changes in MDA levels among the control, DXR-treated groups, or supplemented groups that received additional natural antioxidant foods. SOD enzyme levels were decreased in rats treated with DXR. PA prevented the decrease at low doses of DXR. DXR treatment decreased CAT enzyme levels, but additional PA and hazelnut consumption increased these levels at low cumulative doses. XO enzyme levels were decreased in AGEX and hazelnut groups, but PA prevented the decrease. CK levels were elevated after DXR administration, indicating myocardial injury, but PA significantly reversed this. Although there were no differences histopathologically between AGEX, PA, and hazelnut groups, the protective effects of AGEX and PA were evident in electron microscopy. In conclusion, the positive effects of natural antioxidant foods on the prevention of DXR-induced cardiac injury could not be clearly shown on the basis of antioxidant enzymes. However, the electron microscopic changes clearly demonstrated the protective effects of AGEX and PA. The supplementation of these antioxidant foods over longer periods may show more definitive results. Human studies with different doses are needed to evaluate the effects of these foods on the human heart.

Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy.

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.

Visual and brainstem auditory evoked potentials in children with headache.

BACKGROUND: Headache is a common problem in the pediatric population. The purpose of the present study was to evaluate visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) in children with headache. METHODS: Thirty-seven children fulfilling the International Headache Society Criteria for a diagnosis of migraine, 35 children with tension-type headache and 40 healthy children (control group) were enrolled in the study. RESULTS: The mean age of patients and controls was 10.4 years. P100 latency and amplitudes of migraine patients were significantly higher than children with tension-type headache and control subjects. Children with tension-type headache also had higher P100 latency and amplitude values than control subjects but there was no statistical difference. BAEP responses were similar between all groups. CONCLUSION: Measurement of VEP latency and amplitude is a valuable and reliable test for the diagnosis of migraine and can be used safely in childhood.

Minimal change nephropathy in a 7-year-old boy with Rosai-Dorfman disease.

Rosai-Dorfman (R-D) disease is a benign lympho-histiocytosis of the lymphoid system. Immune derangement due to cytokine over-expression (tumor necrosis factor (TNF), interleukin (IL)-1b and IL-6) has been considered the cause of R-D disease. We present a 7-year-old boy with R-D disease who developed minimal change nephropathy (MCN) during the progression of R-D disease. The patient was resistant to oral prednisolone; and the remission of both R-D disease and MCN was achieved with oral cyclophosphamide (2 mg/kg, 12 weeks). MCN, the most common cause of nephrotic syndrome in childhood, is generally accepted to emerge by way of cytokine derangement. Correlation between R-D disease activity and the development and remission of nephrotic syndrome in our case suggested that nephrotic syndrome had been induced through some R-D disease-related immune mechanisms.

Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid.

Valproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbances including anorexia and nausea, and hepatoxicity. As to its dose-dependent side effects are the weight loss, tremor, skin eruption and the alopecia. In this study we aimed to put forward the biotinidase deficiency considered as a possible cause of alopecia in the rats administered with valproic acid, and the correlation between liver and serum biotinidase enzyme activities (BEA) and transaminases, albumin and serum valproic acid levels. In our study, 4 groups of which one of them was a control group, each consisting of 15 male Wistar rats was organized. 200, 400, and 600 mg/kg/day of VPA, and distilled water, two divided doses per day, were administered per orally to VPA-1, VPA-2, VPA-3, and control group, respectively, in 60 days. Their serum and liver biotinidase enzyme activities, serum AST, ALT, albumin, and valproic acid levels were measured. Alopecia was seen in the subjects of 6.6% of VPA-1, 13.3% of VPA-2, and 26.6% of VPA-3. Significant difference in the liver tissues BEA was noted only between VPA-3 and the control group. Reductions were observed both in the liver tissues BEA and the serum BEA levels, which are inversely proportional to the VPA doses. A positive correlation between the liver biotinidase enzyme activities and the serum valproic acid levels, and the negative correlation between the liver tissues biotinidase activities and the serum valproic acid levels were noted, respectively. As a conclusion, the partial alopecia which is an initial symptom of reduced biotinidase activity may also be created depending on the reduction of biotinidase activity during valproic acid therapy. The alopecia which may further be observed in the patients receiving valproic acid therapy may be prevented by means of administration of biotin in a dose of 10 mg/day.

Bone mass toxicity associated with inhalation exposure to toluene.

The inhalation of a wide range of organic solvents has become popular among young adults. Toluene is one of the most commonly used solvents in industry; it is easily available and convenient to use. Many toxicologic effects on biological systems secondary to deliberate inhalation of toluene have been reported, but investigations on adverse effects associated with bone morbidity is limited. The purpose of this study is to determine bone mineralization and investigate the adverse effects of toluene on bone. The bone mineral density and content of the femoral neck of mice exposed to toluene at 300 ppm for 8 wk were measured by dual X-ray absorptiometry and found significantly reduced compared to the control group. Chronic exposure to toluene was found to affect bone metabolism, and toluene-induced changes could contribute to bone resorption and inhibition of bone formation. Toluene seems to be the responsible component for the demineralizating effects of commonly abused substances, and medical doctors must promote their education about the health hazards in those who abuse solvents especially in areas where inhalant abuse is endemic.

Evaluation of visual evoked potentials in children with headache.

Headache is a common problem in childhood. Visual evoked potential (VEP) P100 latencies were recorded in children with headache. Sixty-four patients, aged 10.7 +/- 1.2 years, met the criteria of the International Headache Society for the diagnosis of migraine. Fifty-eight patients, aged 10.2 +/- 1.3 years, with tension headache and 56 healthy subjects, aged 10.3 +/- 1.3 years, as the control group were also studied. Patients with migraine had slightly longer P100 latencies than the other two groups. We conclude that VEP latency recording is a valuable test in the diagnosis of migraine, and can be safely used in children.

Morbidity and mortality characteristics of infants hospitalized in the Pediatrics Department of the largest Turkish military hospital in 2001.

A descriptive study was conducted in the pediatric inpatient unit of Gulhane Military Medical Academy, to investigate the morbidity and mortality characteristics of 532 infants hospitalized between January 1 and December 31, 2001, for treatment purposes. Of the study participants, 55.8% were boys and 44.2% were girls. The most common cause of hospitalization was neonatal hyperbilirubinemia (19.7%). The most common admission month was January (12.4%). Of 532 infants, 510 (95.9%) were discharged, whereas 22 patients died in the hospital. Twenty-one patients died in the neonatal period, and respiratory distress syndrome and neonatal sepsis were identified as the most common causes of death. Our finding of associations between male gender and low birth weight and hospital death is consistent with previous knowledge. Despite the high frequencies of pneumonia and gastroenteritis as admission diagnoses, the finding of only one pneumonia-related death and no gastroenteritis-related deaths in the study population is pleasing.

Cardiac troponin-I, brain natriuretic peptide and endothelin-1 levels in a rat model of doxorubicin-induced cardiac injury.

BACKGROUND: Cardiotoxicity, during or after therapy, is the most serious side effect of doxorubicin (DXR). The risk of developing cardiac impairment increases concomitantly with an increase in the cumulative dose of DXR. AIM: The aim was to evaluate the levels of cardiac troponin-I (cTnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) in DXR induced cardiac injury. MATERIALS AND METHODS: Thirty-nine Wistar albino rats were divided into three groups; a control group and two-study groups that received low-dose DXR (LDD) and high-dose DXR (HDD) in a weekly schedule for reaching a cumulative dose. RESULTS: Serum cTnI level was significantly increased in both LDD and HDD-treated groups. Although serum BNP was not significantly increased either LDD or HDD-treated groups, ET-1 levels was significantly increased in only HDD-treated groups. Histopathologic injury was more evident in HDD-treated group. CONCLUSIONS: Serum cTnI was increased even in LDD and parallel to it low cardiac injury induced by DXR. In the low-dose group, BNP and ET-1 levels were not elevated significant as cTnI despite cardiac injury. Thus, cTnI may be a predictive marker in of DXR-induced cardiotoxicity.

The use of the corpus cavernosum for the administration of phenobarbital: an experimental study in dogs.

Status epilepticus (SE) is classically defined as a generalized tonic-clonic seizure lasting longer than 30 min. Prolonged seizure activity can be resulted in irreversible cerebral injury. In addition, the existence evidence suggests that the longer the duration of the seizure activity is less likely to be controlled. The intravenous (IV) access is frequently difficult during SE, especially in infants and neonates. On the other hand, it has been demonstrated that high volumes of fluid can be injected into the corpora cavernosa. In this study, phenobarbital (PB) was administered to dogs using both IV and intracavernous (IC) routes with a dose of 20 mg/kg. The time period required to establish the IC route was less than 5 s. The levels of PB in the blood were measured and all results were compared. There was no statistically significant difference between the IV and IC administration with regard of the blood PB levels. Within 48 h of the experiment, none of animals demonstrated any evidence of infection or disability. Our findings suggest that the IC route may be an alternative route for the administration of PB when venous access is not immediately available or if it is not possible to achieve.

Acrocallosal syndrome: report of five Turkish patients.

Acrocallosal syndrome is characterized by agenesis of the corpus callosum, craniofacial anomalies, psychomotor retardation, and polydactyly. The clinical spectrum of this syndrome is broader than previous reports suggest. Five Turkish patients including dizygotic twins are reported.

Hemolytic disease of the newborn due to isoimmunization with anti-E antibodies: a case report.

Minor blood group hemolytic disease is extremely rare, since the overall potency of minor blood groups in inducing antibodies is significantly lower when compared with that of Rh (D) antigen. We hereby report a very rare case of severe neonatal anti-E hemolytic disease due to E minor blood group incompatibility. A term newborn born to a 27-year-old, gravida 3, para 3 mother was referred due to a high and increasing serum bilirubin level despite phototherapy on the 4th day of life. On admission physical examination was normal except for the jaundice, and results of the laboratory investigation demonstrated a moderate-to-severe anemia (hemoglobin 7.8 g/dl) and a severe hemolytic hyperbilirubinemia (serum total and indirect bilirubin levels 36 mg/ dl and 32.8 mg/dl, respectively; reticulocyte count 15%; and a positive direct antiglobulin test). As there was no apparent cause of the hemolytic disease such as Rh or ABO incompatibilities, further investigation (a positive indirect antiglobulin test and a positive irregular anti-E antibody in both the patient and mother, and minor blood group antigen profiles in family members compatible with E minor blood group isoimmunization) revealed the presence of anti-E hemolytic disease due to E minor blood group incompatibility. Two exchange transfusions with a 12-hour-interval were performed with minor blood group compatible fresh whole blood, and the patient was discharged in a healthy condition on the 10th postnatal day. If the most common causes of severe neonatal hemolytic disease such as Rh and ABO incompatibilities cannot be demonstrated in a newborn with significant hemolytic hyperbilirubinemia, anti-E hemolytic disease should strongly be considered in differential diagnosis. It should be kept in mind that a very severe from of minor group antibody hemolytic disease characterized by anemia and severe hyperbilirubinemia many exchange transfusions may be encountered during the course of the disease.

Evaluation of bone mineral density in children with cerebral palsy.

In the present study, bone mineral density of 40 children with cerebral palsy (study group) and the effects of various risk factors on bone mineralization in these children were investigated by comparing with 40 age-matched healthy children (control group). Weight, height, skinfold thickness, body-mass index measurements, and serum levels of calcium, phosphorus, alkaline phosphatase and 25 OH vitamin D were not significantly different between the study and control groups (p>0.05). The mean bone mineral density value of the study group measured by dual-energy X-ray absorptiometry method at L2-L4 levels of lumbar vertebrae was significantly lower than that of the control group (p<0.05). When the patients in the study group were assessed with respect to ambulation status, pattern of involvement, calcium and energy intakes, and whether or not they had taken and/or were taking a regular physical therapy program, there was a significant difference only between the hemiplegic and tetraplegic patients (p<0.05), while there were no significant differences among the patients who were ambulant versus non-ambulant, who had sufficient versus insufficient calcium and energy intakes, and who did and did not take a regular physical therapy (p>0.05). Although the ambulatory status, quantity of calcium and energy intakes, and the presence or absence of a physical therapy program had no effects on bone mineral density values of the children with cerebral palsy in this study, the exact factors and mechanisms responsible for the reduced bone mineral density in children with cerebral palsy should be investigated in further large-scale studies considering the increased risk of pathological fractures in these patients.

Antioxidant enzymes and lipid peroxidation in adolescents with inhalant abuse.

Glue and thinner sniffing is a serious medical problem since the volatile constituents of these substances can lead to severe damage to bone marrow, liver, kidney, brain, and heart. The exact mechanisms responsible for tissue and organ damage in children with inhalant abuse have not yet been determined. In this study, we aimed to determine the levels of antioxidant enzymes and malondialdehyde in children with inhalant abuse. Erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, erythrocyte superoxide dismutase (SOD) activity, and erythrocyte and plasma malondialdehyde (MDA) levels were measured as biological markers of oxidative damage and lipid peroxidation in 37 glue and thinner (inhalant) abusers. The levels were compared with those of the 27 well-matched healthy adolescents. Erythrocyte SOD activity and erythrocyte and plasma MDA levels were significantly higher, whereas erythrocyte and plasma GSH-Px activities were significantly lower in children with inhalant abuse when compared to controls (p<0.01). These findings imply that chronic inhalation of volatile substances can alter the levels of antioxidant enzymes including SOD and GSH-Px, and can increase lipid peroxidation in adolescent abusers.

Evaluation of bone mineral density in chronic glue sniffers.

Although acute and chronic toxic effects of inhalant (glue) abuse have been well demonstrated on many organ systems, the effects on the skeletal system and bone mineral content of young people with this addiction have, to our knowledge, not yet been investigated by bone mineral density measurement. In the present study bone mineral density was measured by the dual-energy X-ray absorptiometry method in 25 children and adolescents with inhalant abuse and compared with that of a control group (n=30) to detect whether there was any delay in bone development or any decrease in bone mass. Chronological age, height and weight, serum calcium, phosphorus and alkaline phosphatase levels of the study group were not significantly different from those of the control group (p>0.05), whereas bone mineral density was significantly reduced in the study group (p=0.001). Teenagers with glue vapor abuse may carry an increased risk of future fracture even though the exact mechanism(s) responsible for the toxicitiy of glue vapor on bone metabolism remains to be determined. To ascertain the exact component of glue responsible for bone demineralisation may be of value in proposing a change in the composition of the glue. Education and/or rehabilitation programs currently have the greatest importance in preventing and overcoming the harmful effects of this public health problem which is so common in young children and adolescents.

Plasma levels of trace elements have an implication on interferon treatment of children with chronic hepatitis B infection.

This study evaluated the plasma levels of trace elements in children with chronic hepatitis B virus (HBV) infection and assessed whether they can be a factor that affects the response to interferon alpha (IFN-alpha) treatment. The study included 35 cases (ten girls, 25 boys) aged 3-13 years with chronic HBV infection and the control group. Plasma levels of copper (Cu), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn) were measured before IFN-alpha treatment and biochemical, virological, and histopathologic response to treatment were assessed. Children were followed for at least 15 months. Although plasma Cu levels showed no difference between the groups, Mn, Mo, Se, and Zn levels were significantly lower in the study group before treatment. Fourteen cases (40%) showed biochemical response; 17 (48.6%) showed virological response; 16 (47.6%) showed histopathologic response, and ten (28.6%) showed response according to all three parameters. Plasma Cu and Mn levels of patients with triple response showed no difference; but Mo, Se, and Zn levels were significantly lower (p < 0.001) in the study group. No difference was observed between responders and nonresponders (p > 0.05). Plasma levels of Mn, Mo, Se, and Zn are lower in children with chronic HBV infection compared to healthy children. The pretreatment levels of these elements did not show difference between responders and nonresponders to IFN-alpha.

Evaluation of renal tubular function in children taking anti-epileptic treatment.

AIM: To assess the effects of anti-epileptic drugs on renal tubular function. METHODS: Urinary N-acetyl-beta-D-glucosaminidase activity was measured in 114 epileptic children (mean age 5.6 +/- 1.1 years) who were undergoing monotherapy with valproate (n = 46), carbamazepine (n = 34), lamotrigine (n = 13) and combined therapy with valproate+carbamazepine (n = 21). RESULTS: The urinary N-acetyl-beta-D-glucosaminidase index of valproate (P < 0.01), carbamazepine (P < 0.05) and polytherapy group (P < 0.01) were significantly elevated when compared with that of the control group. No significant difference in N-acetyl-beta-D-glucosaminidase levels was found between the lamotrigine group and the control subjects. We found that the distribution of the N-acetyl-beta-D-glucosaminidase values of patients depended significantly on the length of therapy (P < 0.01). The level of urinary excretion of N-acetyl-beta-D-glucosaminidase was significantly higher in the patients who were taking long-term treatment (>10 years) with valproate, carbamazepine and combined therapy than those taking therapy shorter than 10 years (P < 0.01). The mean serum concentrations of valproate and carbamazepine were 68.7 +/- 17.44 microg/mL and 5.41 +/- 1.23 microg/mL, respectively. There was a significant correlation between the serum concentration of valproate and urinary N-acetyl-beta-D-glucosaminidase levels (r = 0.44, P < 0.01). There was also a significant correlation between the serum concentration of carbamazepine and N-acetyl-beta-D-glucosaminidase excretion (r = 0.52, P < 0.01). CONCLUSION: The present study demonstrated that in patients treated with valproate and carbamazepine, an impairment of tubular function can be present, whereas lamotrigine does not cause any significant change.

Recurrent Streptococcus pneumoniae meningitis in a child with traumatic anterior cranial base defect.

Acute bacterial meningitis is a potentially life-threatening infection of the cranial and spinal leptomeninges. Recurrent episodes of meningitis are rarely seen, but when they occur, an extensive investigation has to be made to find out responsible factors. A single episode of acute meningitis may result from bacteriemia, but when followed by recurrent meningitis in pediatric patients, other possible routes of the bacteria invasion to the cerebrospinal fluid (CSF) should be considered. Patients with head injury have the highest risk of acquiring recurrent bacterial meningitis, followed by patients with a congenital anatomic lesion of the skull or duramater, such as meningomyelocele. The underlying cause is a transdural communication between the meningeal space and paranasal sinuses or skin. The first attack of meningitis may occur several weeks to 12 years after the head injury. In addition, recurrent bacterial meningitis may be due to disorders of the immune system, such as complement deficiency. We report a 14-year-old boy, who suffered from recurrent Streptococcus pneumoniae meningitis due to a well-defined defect at the ethmoid roof after a head trauma.

Familial high factor VIII level in a child with necrotizing fasciitis complicating primary varicella infection.

This article describes an unusual association of familial high plasma factor VIII level and necrotizing fasciitis in a 4-year-old girl with primary varicella infection.