Effect of hypothyroid status on lipid peroxidation, antioxidant defences and susceptibility to oxidative stress under amiodarone therapy in female rats

The effect of free radicals on human beings has attracted considerable attention due to their close relation to health and disease. This study was carried out to investigate the antioxidant status in thyroid and liver due to treatment with amiodarone [AM] and the relationship between AM treatment and thyroid function in case of pre-existence of hypothyroidism. The present study comprised of two experiments, each of them extended for 2 months. The first one was designed to induce hypothyroidism and the second for treatment with AM. Serum malondialdehyde [MDA] and reduced glutathione [GSH] levels were measured as indicators of redox status. The levels of serum triiodothyronine [T3], thyroxine [T4] levels and thyroid stimulating hormone [TSH] were measured the agonist/antagonist interactions between the drug and thyroid hormones. Liver enzymes-Alanine aminotransaminase [ALT] and Aspartate aminotransaminase [AST] activities-and lipid parameters were measured in serum as well. In addition, hisopathological examinations for thyroid and liver tissues were done. The results showed that: 1] serum T3 and T4 levels were increased, while TSH levels were decreased in hypothyroid AM treated group, whereas in euthyroid AM treated group, serum T3 was decreased but serum T4 and TSH levels increased. 2] total cholesterol and LDL increased in both AM treated groups showing a state of hyperlipidemia. 3] serum MDA level was increased while serum GSH was decreased in AM treated hypothyroid group and in euthyroid AM treated one as well, inducing a state of oxidative stress. Serum MDA levels were decreased while serum GSH were increased in Hypo+. 4] ALT and AST increased in all AM treated groups. 5] hisopathological examination of thyroid and liver tissues showed some structural abnormalities due to AM treatment. Based on these results, patients with hypothyroidism should be monitored periodically their thyroid and liver functions during AM therapy due to its stimulation for the formation of reactive oxygen species, causing oxidative damage in both liver and thyroid functions and their tissues. These findings suggested that a state of hypothyroidism may exert beneficial protective and curative effects on this situation by decreasing T3, T4, ALT and AST levels, attenuating the endogenous antioxidant levels and decreasing lipid peroxidation

Sanjad Sakati syndrome: a case series from Jordan

Sanjad Sakati syndrome is a rare autosomal recessive disorder that has been described in Arabs. We report 8 patients from 7 Jordanian families, 6 of whom underwent genetic testing and were found to have a 12 bp [155-166 del] deletion within the tubulin-specific chaperone E [TBCE gene] in exon 3 at lq42-43. All patients had severe growth retardation, distinct phenotypic features and hypoparathyroidism. Parental consanguinity was recorded in all families. This is the first genetically proven case series of Sanjad Sakati syndrome in Jordan

Erythropoietin in the serum and cerebrospinal fluid of epileptic children

Recent years' research has revealed a specific, neuroprotective enythropoietin [EPO] system in the central and peripheral nervous system, that is upregulated by neuronal damage due to brain hypoxia. Few studies have investigated the endogenous production of EPO in human nervous system. The presence, origin and clinical importance of EPO in epileptic children are investigated for the first time. Forty-five children divided into 3 groups were studied. Group I included 15 recently diagnosed epileptics, not receiving antiepileptic drugs [AEDs], aged 3.8-15 years. Group II consisted of 15 refractory epileptics on AEDs for more than 1 year, aged 3.5-14.7 years. Fifteen healthy children of matched age, sex and socioeconomic status represented groups III [control group]. All children were suffering no hematological, neurological or renal diseases. They were subjected to detailed history, thorough clinical examination an routine investigations [CBC, urea, creatinine, ESR, CRP]. CT brain and EEG were done for epileptic children. Serum levels of albumin [by a colorimetric reaction] and serum prealbumin levels and CSF levels of albumin and prealbumin [by nephelometry] were measured for all children. Serum and CSF levels of EPO were assessed 12 hours after epileptic fits and on admission of control children [using erythropoietin ELISA kit]. Family history was positive for epilepsy in 16.67% of our epileptic children. Their most common types of convulsions were generalized tonic-clonic [GTC], generalized tonic [GT], myoclonic then focal seizures. CT brain was normal in the majority. A minority showed brain atrophy, calcification, hemorrhage, and infarction. EEG showed focal [FEA], generalized [GEA] and multifiocal epileptic activities among our recent epileptics while diffuse slowing [DS] and burst suppression were additional EGG findings among refractory epileptics. The serum and CSF levels of albumin, and prealbumin were normal just as control levels with no correlation with other demographic, clinical and laboratory studied variables. Q albumin was normal in epileptic children indicating the integrity of the blood brain barrier [BBB]. Q prealbumin was as expected markedly higher than Q albumin among epileptic and control children as it has a well known CNS synthesis. The serum levels of EPO were not significantly different in epileptic children, while its CSF levels were significantly higher compared to control children. The degree of elevation of the CSF levels of EPO among refractory epileptics was significantly lesser than that observed among recent epileptics. The CSF levels of EPO in recent epileptics were directly proportionate to the duration of the epileptic fits, while they were inversely proportionate to it in refractory epileptics; a disturbed and/or exhausted neuroprotective role of EPO among prolonged and refractory epileptics may be an explanation. So far; as the Q EPO is much higher [as Q prealbumin] than Q albumin, as there is no significant correlation between CSF and serum levels of EPO among epileptics, as there is no significant correlation between CSF levels EPO and Q albumin and as there is no significant correlation between Q EPO and Q albumin among epileptics and control children; it is concluded that the origin of this CSF erythropoietin is the brain; as a neuroprotective cytokine against neuronal damage caused by the epileptic fits, with the duration of the fit as a determinant factor. As commercially available forms of genetically engineered EPO are safely used for several indications in pediatrics; it is concluded that EPO is an ideal compound to study and it should be thoroughly evaluated in epileptic children, specially the refractory epilepsies and those with prolonged epileptic fits considering a possible therapeutic potential for EPO. It is also concluded that EPO in the CSF of epileptic children is a marker of epileptic fits and has its clinical indications in prognosis and therapeutic intervention

Hormonal profile among children with short stature

Linear growth occurs in 3 phases. During fetal and early infant life, growth is largely regulated by nutrition, during childhood by growth hormone [GH] and during puberty by GH and sex steroids. Short stature may be the normal expression of genetic potential, in which case the growth rate is normal at least at the 25[th] percentile, or it may be the result of a condition causing growth failure with a growth rate below the appropriate growth velocity for age. Short stature has been shown to have far reaching effects on psychological well being including poor academic achievement, behavioral problems, morbidity related to the underlying cause and increased risk for reduced bone mass. One hundred fifty-nine patients divided into 4 groups were studied. Group 1 [Pituitary dwarf] consisted of 26 patients [16 males and 10 females] aged 4-12 years. Group II [Congenital hypothyroidism] included 23 patients [14 males and 9 females] aged 2-12 years. Group III [Down's syndrome] consisted of 10 patients [5 males and 5 females] aged 3-12 years. A hundred apparently healthy children [50 males and 50 females] aged 2.5-12 years were considered as [Control group] group IV. All children were examined thoroughly, anthropometric measurements [14 items] were evaluated according to percentiles and Z-score diagrams. Bone age was determined by plain X-ray left wrist. Hormonal study was done including T[3], T[4], TSH, overnight urinary growth hormone [GH] and creatinine. Serum growth hormone [insulin-induced hypoglycemia test] and insulin like growth factor-1 [IGF-1] were measured for the pituitary dwarf group. The height, sitting height and arm span measurements showed a marked decrease below normal mean Z-scor e [more than -2SD] in the three studied groups of patients. Hormonal profile: There was a significant decrease in serum levels of both T[3] and T[4] in congenital hypothyroidism and insignificant change in the other two groups. 3 patients from Down's syndrome group reached a hypothyroidal level of T[3], T[4], and TSH. Generally urinary growth hormone showed a significant decrease in the three studied groups of patients. Pituitary dwarf group showed a significant decrease in both serum and urinary growth hormones and also serum IGF-1 with a positive correlation between serum growth hormone and both urinary growth hormone and serum IGF-1. Height, sitting height and arm span are simple and accurate measurements for early detection and follow up of the short child. Assessment of the thyroid hormonal profile is essential as early as possible in all children with short stature with and without clinical stigmata of hypothyroidism. Determination of urinary growth hormone is as accurate as serum GH, moreover it is easier. Measurement of serum IGF-1 is an important era in diagnosis of short stature

Genetic profile among children with short stature

Human growth starts at conception and proceeds through various identifiable developmental stages. The process of growth depends on both genetic and environmental factors that combine to determine an individual's eventual height. Many genes have been identified and their mutations have been shown to be responsible for abnormal growth in humans and animals. Dermatoglyphics can be used to study the participation of genetic factors in diseases while cytogenetic evaluation can be used to detect and study the responsible chromosomes and genes. Fifty-nine short stature patients were included in this study allocated into four groups. Group 1 [Pituitary dwarf] consisted of 26 patients [16 males and 10 females], aged 4-12 years. Group II [Congenital hypothyroidism], included 23 patients [14 males and 9 females], aged 2-12 years. Group III [Down's syndrome] involved 10 patients [5 males and 5 females], aged 3-12 years. A hundred clinically healthy children [50 males and 50 females] of matched age, sex and socioeconomic status represented group IV [control group] aged 2.5-12 years. All patients and control children were subjected to detailed history, family pedigree, thorough clinical examination, anthropometric measurements [14 items, plotted into percentile curves and z-scores], bone age determination by plain x-ray left wrist, IQ assessment using Stanford Binnet test, and chromosomal studies including dermatoglyphics by Ink method, karyotyping and Sister Chromatid Exchange [SCE] by Hockest Giemsa method. Consanguinity was positive in about 50% in groups I and III and about 80% in group II. Patients showed significantly low z-scores for height [mean = -3.67, -3.52, -3.31], sitting height [mean = -3.09, -2.59, -2.06] and arm span [mean = -3.28, -2.45, -2.34] for groups I, II and III respectively. Dermatoglyphic study: the finger tip pattern in groups I and II showed a high frequency of radial loops, on the other hand there was a high frequency of ulnar loops in group III. The total ridge count [TRC] was significantly decreased more in group III than group II and insignificantly different in group I when compare to control children, Similarly [atd] angle was significantly increaed [both hands] in groups II and III, while it was insignificantly different in group I in comparison to control children. Total [a-b] ridge count was slower among patients of groups II and III when compared to control but it was significantly higher among patients of group I. The thenar and hypothenar study showed an increase in the pattern in groups I, II and III comparable to control. Interestingly a significant hypothenar whorl pattern in left hand was found in two families of group I. As regards the chromosomal study, both groups I and III showed high frequency of SCE. Also, there was an increase in structural aberrations in both groups [more in group III than group I]. High frequency of consanguinity may be an explanation. On the other hand, the two families showing the special hypothenar whorl pattern also had high frequency SCE. Dermatoglyphic data in this study [Increase in the pattern in thenar and hypothenar areas and increase in [atd] angle and decrease [TRC] could be considered as a diagnostic tool in the assessment of the short child. So, it is recommended to conduct a well-designed nation-wide study of dermatoglyphic, chromosomal and genetic findings for the short child and his family to find out the genetic basis of short stature among Egyptian children

Serum prolactin and creatine kinase levels in epileptic and non-epileptic seizures

The adverse effects of anticonvulsant drugs, duration and expense of therapy and social implications, make it essential for accurate diagnosis before starting treatment. Many patients being treated as epileptics are not actually so. Moreover the coexistence of pseudoseizures with epilepsy is high. There is no single exposure, biochemical marker to differentiate between epileptic and non epileptic seizures [NES]. Ninety children were studied. They were subgrouped into 4 groups. Group I included 30 children with recent epileptic fits, aged 2-12 years. Group II consisted of 15 children with recent typical febrile seizures, aged 1-4.75 years. Group III involved 15 children with recent non-epileptic seizures, aged 5.2-12.7 years. Thirty clinically healthy children aged 3-12 years represented group IV [control group]. Thorough history and clinical examination confirmed diagnosis and established exclusion criteria. CT brain, EEG and EMG imaging studies were done for all patients. Peripheral white blood cell count [WBCs], serum creatine kinase [CK] and prolactin levels were measured within lapse time [15-120 minutes] and 24 hrs post-ictally for all patients and once for control children. Post-ictal symptoms were present in more than 2/3 of epileptic seizures and 20% only of non-epileptic fits. WBCs and serum prolactin levels showed a transient early; while serum CK levels had a late post-ictal significant increase after generalized epileptic fits and to a much lower extent following focal and nonepileptic fits. The generalized tonic-clonic seizures [GTCS] showed higher elevation than other types of generalized epileptic fits. The three parameters showed a positive correlation with duration of seizures and a negative correlation with lapse time. Peripheral WBCs and serum prolactin returned to near normal levels one day post-ictally, while serum CK started to show a significant increase only 24 hrs after seizures. Serum prolactin levels were elevated more than twice and serum CK levels increased by more than 20 U/L in a high percentage of epileptic GTC seizures. The integrated interpretation of post-ictal symptoms, early assessment of peripheral WBCs and serum prolactin [<2 hrs] and late measurement of serum CK levels [>24 hrs] can compensate for our clinical uncertainty between epileptic and non-epileptic seizures before having to resort to more sophisticated and expensive investigations

Antiphospholipid antibodies, fasting insulin, and glycosylated haemoglobin in children with type I diabetes in relation to some clinical risk factors

Fifty children divided into 3 groups were studied. Group I included 10 children with recent onset diabetes type I [<6 months]. Their ages ranged from 6-11 years. Group II consisted of 20 children with prolonged diabetes [>5 years] aged 12-15 years. Twenty non-diabetic children aged 6-15 years represented group lll. All studied children were not suffering from any other autoimmune disorder, nor receiving a medication, which is known to affect any of the studied parameters. All children were subjected to detailed history taking, thorough clinical examination and venipuncture while fasting to measure HBA[1c], fasting insulin and antiphospholipid antibodies [APA] [lgG and 1gM]. It was found that duration of diabetes carries on a more significant effect on both SBP and DBP than the diabetes per Se. WHR reached risky levels [>0.8 in girls and>0.9 in boys] in 30% of children with recent onset diabetes, while BMI reached risky levels [>25 kg/m[2]] in only 10% of them. Fifty percent of children with prolonged diabetes [>5 years] had risky high WHR, while only 30%of them had risky high BMI. So, WHR, was found to be a more sensitive risk factor than BMI. Fasting insulin [Fl] levels were significantly lower in all diabetic children [with recent onset and with prolonged disease duration] than in non diabetic children [mean 3.8, 5.2 and 11.45 uU/ml respectively]. F! was found to be significantly affected by APA [lgG] and BP percentiles [P=0.002 and 0.048 in order]. APA [lgG] was significantly higher in 60%of children with recent onset diabetes, and only in 45% of those with diabetes for>5 years [mean 12.39 and 9.72 GPL/ml respectively]. APA [IgM] showed a less marked increase with diabetes, with high levels in only 20% of recent onset diabetics and 5% of those with prolonged diabetes [mean 8.52 and 6.945 MPL/ml respectively]. APA levels [lgG and 1gM] were affected significantly by WHR, BP percentiles and HBA[1c]. APA especially IgG can be added to the diagnostic autoantibodies of type I diabetes and WHR and BP percentiles to the control regimen [along with HBA[1c]] among children with type I diabetes

Anti-Helicobacter antibodies and fasting gastrin concentrations in children with recurrent abdominal pain

Fifty children divided into 2 groups were studied. Group I included 30 children with non organic recurrent abdominal pain [RAP] as defined by Apley and Naish, aged 3.5-11.8 years. Group II [control group] consisted of 20 apparently healthy children with no gastrointestinal symptoms nor signs, aged 4 -10.5 years. All children were subjected to detailed history taking and thorough physical examination, urine and stool analysis, complete blood count and abdominal ultrasonography. Anti-Helicobacter IgG antibodies were investigated by immunoassay and fasting gastrin concentrations were measured using the Double Antibody Gastrin procedure for all children. In the present study, children with and without RAP were well matched for age and sex. The mean fasting gastrin concentration was not significantly related to RAP. Thirty percent [30%] of studied children with RAP were seropositive for H-pylori compared to 15% only of control children. In children seropositive for H. Pylori, there were no significant relations between sex, age and fasting gastrin concentration to occurrence of RAP. Similarly, the relation of sex, age and fasting gastrin concentration to occurrence of RAP was not significant among children seronegative for H. pylori. Evaluation of the differences between seropositive and seronegative children in our study showed that H. pylori infection increased fasting gastrin concentration by more than 100%. It could be concluded that H. pylori is a common infection in our children. It results in a marked rise of fasting gastrin with its possible clinicopathologic consequences. However, H. pylori infection and hypergastrinemia showed no significant causal relationship to RAP at the currently available clinical characteristics

Gamma aminobutyric acid [GABA] and glutamate levels in the csf of epileptic children

Thirty-one children divided into 3 groups were studied. Group I included 13 neurologically free children, aged 3-9 years and not receiving any medications. Group II consisted of 7 recently diagnosed non medicated epileptic children, aged 3.5-8 years. Eleven medicated epileptic children; aged 4-9 years represented group III. All children were examined thoroughly. EEG and brain CT scan were done for epileptic children. Gamma Aminobutyric acid [GABA] and Glutamate levels in CSF were assessed for all children by HPLC. The mean CSF levels of GABA were lowest in non-medicated epileptic children. Control of the seizures by anti-epileptic drugs [AEDs] was associated by a concomitant re-increase in the CSF GABA levels. The mean glutamate CSF levels did not differ significantly among the three studied groups. Nevertheless, it was noticed that the GABA / Glutamate ratio was higher in medicated than in non-medicated epileptic children. It could be concluded that CSF GABA levels as well as the GABA / Glutamate ratio can reliably monitor the epileptic control by pharmacotherapy

Urinary retinol binding protein, albumin, total protein concentrations and blood electrolytes in term and preterm neonates

Fifty neonates were included in this study, divided into two groups. Group 1[control group] consisted of 22 healthy neonates. Group 1A included 12 full term, 3 females and 9 males. Their gestational ages ranged between 37-39 weeks [mean 37.58 +/- 0.76 weeks]. Group 1B included 10 preterm neonates, 4 females and 6 males. Their gestational ages ranged between 28-34 weeks [mean 30.8 +/- 2.44 weeks]. Group II included 28 sick neonates admitted to the neonatal care unit of the pediatric department of El-Menoufiya University hospital and El-Menshawy general hospital. 10 had asphyxia, 5 had pneumonia, 7 had hyaline membrane disease and 6 had acute hemolysis. All the neonates were under antibiotic therapy. Group IIA consisted of 14 full term neonates, 2 females and 12 males. Their gestational ages ranged between 37-40 weeks [mean 37.64 +/- 0.81 weeks]. Group IIB consisted of 14 preterm neonates, 3 females and 11 males. Their gestational ages ranged between 27-35 weeks [mean 30.5 +/- 2.44 weeks]. All the neonates were subjected to thorough clinical history and examination, as well as measurement of serum sodium and potassium, blood urea, serum creatinine, urinary creatinine, total protein excretion, and measurement of urinary excretion of microalbumin and retinol binding protein [RBP] in untimed urine samples by ELIZA technique. The blood urea, microalbuminuria and total proteins were significantly elevated in sick neonates [Group II] compared to healthy neonates [Group I], however the difference was not influenced by the gestational age. No significant difference could be detected in serum sodium, potassium, serum creatinine and urinary creatinine between both groups. Measurement of RBP revealed that the healthy preterm neonates [Group IB] had a significantly higher level of RBP compared to the healthy full term [Group IA, P <0.05]. Also, the sick neonates [Group II] had a significantly higher level compared to the healthy ones [Group I, P<0.01]. RBP showed a significant negative correlation with the gestational age and the Apgar score at 1 and 5 minutes, and a significant positive correlation with blood urea and microalbuminuria. Evaluating the renal function by the excretion of RBP and microalbuminuria, showed that RBP was positive in 84% of the cases while microalbuminuria was detected in 30% of the cases only. It can be concluded that Retinol binding protein is an early and specific non-invasive marker of tubular functions. It has the advantage of being able to unmask even subtle cases of kidney injury when other parameters of kidney functions are still within the normal range