HMGCR and ApoE mutations may cause different responses to lipid lowering statin therapy.

Coronary artery disease (CAD) and its complications are the major causes of death in the world. Although statins have been used to lower lipid levels in CAD patients, this goal can not be attained in 1/3 of the patients. The objective of this study was to investigate whether common variations in HMG-CoA Reductase(HMGCR) and Apolipoprotein E (ApoE) genes involved in lipid and statin metabolism modify the effect of statins on serum lipid and lipoprotein concentrations in CAD patients.A hundred  CAD patients were enrolled into the study. At the beginning of the study biochemical measurements were performed to determine the baseline levels performed. Patients were treated with 40 mg atorvastatin for 2 months and biochemical measurements were repeated. According to the post-treatment, LDL-c levels,  patients were divided into 2 groups as non-responders and responders, respectively. The information regarding the risk factors such as smoking, alcohol consumption etc. were also obtained. DNA was isolated from peripheral blood. The presence of rs17244841 ve rs17238540 mutations in HMGCR and ε2, ε3 and ε4 variants of ApoE were determined by using RT-PCR. Results were evaluated statistically. HMGCR mutatations were mostly found in responders and ε4 variant of ApoE was mostly found in non-responders. It was also found that presence of HMGCR mutations causes a significant reduction in total cholesterol and LDL-c levels. Also presence of ε2 variant of ApoE causes a statistically significant increase in trigliseride levels. Our findings should be investigated with other researchers to clarify the mechanism.

The effects of polyphenol-containing antioxidants on oxidative stress and lipid peroxidation in Type 2 diabetes mellitus without complications.

BACKGROUND: The hyperglycemia-induced oxidative stress in diabetes mellitus (DM) is the major factor in the pathogenesis of cardiovascular complications. The phenolic compounds are potent antioxidants that can reverse the factors leading to cardiovascular complications in DM. The aim of this study was to determine the antagonizing effects of a polyphenol-rich antioxidant supplement containing pomegranate extract, green tea extract, and ascorbic acid, on oxidative stress in Type 2 diabetic patients. MATERIALS AND METHODS: A total of 114 male and female non-smokers (56 study, 58 placebo) with Type 2 DM and without any complications were recruited. The blood levels of fasting blood glucose, glycated hemoglobin, LDL, HDL, triglycerides, plasma malondialdehyde (MDA), total glutathione (GSH), hydrogen peroxide, and antioxidant capacity (AOC) were determined at the beginning and at the end of the 3-month trial. The differences of the data changes between the groups were statistically analyzed by Mann-Whitney U test. RESULTS: The study group showed a decrease in LDL and an increase in HDL and the comparison with the difference in placebo group was statistically significant (p<0.001 for LDL and p<0.001 for HDL). Accordingly, as a by-product of lipid peroxidation, plasma MDA was decreased in the study group compared to the placebo group (p<0.001). As an indicator of increased antioxidant defense, total plasma GSH and AOC increased more in the study group compared to control group (p<0.001). CONCLUSIONS: These observations indicated that the polyphenol-rich antioxidant supplement containing pomegranate extract, green tea extract, and ascorbic acid has important antagonizing effects on oxidative stress and lipid peroxidation in patients with Type 2 DM and might be beneficial in preventing cardiovascular complications.

The effects of chronic administration of sumatriptan and dipyrone on serotonergic system in the rat brain: an immunohistochemical study.

OBJECTIVE: To investigate the effects of chronic high dose sumatriptan and dipyrone treatment on central serotonergic system in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats (seven per group) were daily injected with sumatriptan (3 mg/kg), dipyrone (400 mg/kg) or saline for 30 days. The brains of animals were surgically removed and immunohistochemically stained for serotonin. Serotonin-positive stained cells were counted automatically by using a computerized image analysis program. Statistical analysis carried out using one-way ANOVA followed by post hoc Tukey test. RESULTS: A significant decrease in serotonin-positive cells in the brainstem was observed after chronic sumatriptan administration while chronic use of dipyrone induced a significant increase in serotonin-positive cells both in the cortex and midbrain. CONCLUSION: Our data suggest that central serotonergic system might be modified by chronic use of sumatriptan and dipyrone.

Motility, rigidity and turnover of dopamine in the striatum after administration of morphine to rats: a re-evaluation of their mechanisms.

Whether the delayed behavioural activation and the increase in dopamine (DA) turnover in the striatum reflect signs of rebound effects or of counter-regulatory processes directed against locomotor depression and/or muscular rigidity was studied in rats. Administration of a large dose of morphine (30 mg/kg i.p.) induced strong muscular rigidity, which was measured as tonic activity in the electromyogram (EMG). This effect was maximal after one hour and disappeared during the fourth hour. The locomotor activity, on the other hand, disappeared after 30 min and re-appeared during the fourth hour, followed by a locomotor stimulation with a maximum after 4.5 hr. Striatal lesions produced with kainic acid did not affect the complete locomotor depression (akinesia), except by slightly prolonging this effect, and did not influence the delayed locomotor stimulation. These lesions did not inhibit, but, on the contrary, enhanced the increase in striatal concentration of 3,4-dihydroxyphenylacetic acid (DOPAC). Injections of morphine (10 micrograms) into the substantia nigra led to an increase in the level of DOPAC in the ipsilateral, but not the contralateral striatum. These results, in conjunction with those of other authors, suggest that the increase in DA turnover in the striatum and the delayed locomotor stimulation ought to be regarded as actions of morphine on sites different from those mediating muscular rigidity.

The antagonizing effect of aspartic acid on the brain levels of monoamines and free amino acids during the development of tolerance to the physical dependence on morphine.

Since it has been shown in previous study that aspartic acid prevents the development of physical dependence on and tolerance to morphine and antagonizes the abstinence syndrom signs, the biochemical bases of that prevention were investigated in the present study. The brain contents of serotonin, DA, NA, and free amino acids of the rats given aspartic acid and morphine separately and in combination were determined. It has been observed that most of the morphine-induced changes in the brain were normalized in the group given aspartic acid and morphine together. The relative ineffectiveness of aspartic acid in normalizing some amino acid levels decreased by morphine was discussed and some logical explanations were found.

The relationship between morphine, aspartic acid and L-asparaginase in rats.

Morphine and aspartic acid were administered separately and in combination to 80 rats divided into 8 groups. Ten and 20 min following the injections, brain, liver and kidney L-asparaginase activity was determined. Morphine decreased brain and liver L-asparaginase activity and increased that of kidney. Aspartic acid completely antagonized the effect of morphine. Additionally 500 IU/kg L-asparaginase and 5 or 10 mg/kg morphine were i.v. injected into 56 rats divided into 5 groups. L-Asparaginase, which, in turn, increased motor activity, antagonized the morphine-induced hypoactivity and analgesia. These results support our previous findings.

Effects of striatal lesions with kainic acid on morphine-induced "catatonia" and increase of striatal dopamine turnover.

The influence of striatal lesions (head of the caudate nucleus) with kainic acid on "catatonia" and on the increase of the dopamine metabolite DOPAC in the striatum after systemic morphine administration was measured in rats. These lesions strongly prevented the morphine-induced muscular rigidity, measured as activity in the electromyogram EMG) of the gastrocnemius-soleus muscle of non-anesthesized animals. On the other hand, the decrease of locomotion (akinesia) measured using an Animex Activity Meter and an activity wheel, was not prevented or reduced. The lesions did not influence the inhibitory effect of morphine on the activation of flexor alpha-motoneurones, either. These results suggest that the head of the caudate nucleus plays an important role in mediating morphine rigidity, but not akinesia or inhibition of the activation of flexor alpha-motoneurones. Opioid-induced "catatonia" ought to be regarded as a mixture both of rigidity and of akinesia. Morphine led to a rapid decrease, followed by a slow increase of striatal DOPAC concentration. Lesions induced by kainic acid slightly inhibited the decrease and markedly enhanced the increase of DOPAC. Accordingly, an intact nigro-striato-nigral loop is not necessary for the increase of striatal dopamine turnover, observed after morphine administration. The different sites of action, which are likely to mediate all these effects of morphine, are discussed.

Prognostic value of p53, proliferating cell nuclear antigen, and Ki-67 expression in undifferentiated nasopharyngeal carcinomas.

In this study the prognostic importance of p53, proliferating cell nuclear antigen (PCNA), and Ki-67 expression was analyzed along with the clinical parameters in 35 consecutive patients with undifferentiated nasopharyngeal carcinomas. Immunohistochemistry was used to detect p53, PCNA, and Ki-67 staining. Among the clinical findings, stage IV disease (P = 0.01), cranial nerve paralysis (P = 0.02), and lymph node metastasis (P = 0.06) were associated with shorter survival. The p53 positivity correlated with the presence of lymph nodes, but it was not a significant factor to predict the outcome. PCNA expression was not found to be a prognostic indicator. On the other hand, the proliferative value of Ki-67 staining was suggestive of prognosis. A proliferation index of Ki-67 less than 10% indicated longer survival (P = 0.03). There was no correlation between Ki-67 staining and PCNA index. As a result, the prognostic value of Ki-67 may alert the physician to more aggressive and adjuvant treatment modalities.

Persistent neonatal hypoglycemia: an unusual finding of congenital hypothyroidism.

We report a newborn infant who has congenital hypothyroidism associated with profound and persistent neonatal hypoglycemia. Persistent and marked hypoglycemia has not been previously reported in congenital hypothyroidism to our knowledge. The cause of this condition may be reduced glyconeogenesis or insulin clearance.

Thyroid function tests in the newborn infants of preeclamptic women.

The purpose of this study was to identify possible changes in thyroid functions in newborn infants of preeclamptic women. Fifteen neonates (nine boys and six girls) of preeclamptic women and 17 healthy neonates (nine boys and eight girls) for the control group were included in the study. Serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) levels and thyroid gland volumes were determined in both groups. Serum TSH and TT4 levels were not statistically different between the two groups. However, serum TT3 level was 79.22 +/- 40.19 ng/dl in the study group and 40.00 +/- 15.99 ng/dl in control subjects (p < 0.01). The mean right, left and total thyroid volumes were 1.3 +/- 1.2 ml, 1.2 +/- 1.1 ml and 2.4 +/- 2.3 ml in the study group and 0.6 +/- 0.2 ml, 0.6 +/- 0.2 ml, and 1.1 +/- 0.4 ml in the control group, respectively (p < 0.05). The mean thyroid volume/body weight was 0.9 +/- 0.09 ml/kg in the study group and 0.3 +/- 0.06 ml/kg in the control group (p < 0.05). In conclusion, we would like to stress that preeclampsia might be a cause of fetal and neonatal thyroid enlargement and elevated serum TT3 level.

A venous anomaly of the neck.

Vascular anomalies localize mostly in the head and neck region. Besides the complications they present, when they are left untouched, they are cosmetically ugly. A vascular lesion in any part of the body of a child is always bothersome to the parents and may be a problem for the family. The confusion about classification of these lesions and the delay in seeing the physician may adversely affect the child also. There has been a debate concerning the classification of vascular malformations, their clinical presentation, and their treatment modalities. In this paper we reviewed the classification as accepted in the literature and presented a case of huge venous anomaly in the neck region with its angiographic and MRI views and discussed the possible complications and modes of treatment.

Cherubism: a radiological and clinical presentation.

Cherubism is the hereditary form of the fibrous dysplasia of the jaws, but it may be seen sporadically as well. The disease has a self-limited nature and is rarely apparent before the age of two. There is no need to interfere surgically with these lesions of the mandible or the maxilla unless the child is severely affected, i.e. the disease deteriorates respiration, deglutition, vision, or the psychiatric makeup of the child due to cosmetic reasons. The clinical presentation and radiological evaluation of these children are so typical that the pediatrician and pediatric otolaryngologist need to be informed about this rarely seen disease. A case of a cherubic child, with his clinical appearance as well as his radiological evaluation, and discussion about the clinical outcome are presented.

Significant response of radiation induced CNS toxicity to high dose steroid administration.

Treatment of radiation myelopathy remains a challenge. Supportive and rehabilitative therapy is the mainstay of treatment. This article describes a case of central nervous system (CNS) toxicity of radiation with a progressive improvement in the clinicoradiological picture following high dose steroid treatment. A female patient was admitted to the neurology department of our hospital 7 months after a course of radiotherapy in another centre for lingual epidermoid cancer. Neurological examination revealed a heavy spastic quadriplegia syndrome. On MRI examination, T2 weighted hyperintensities were observed in cerebral and cerebellar peduncles, periventricular regions and medulla spinalis at Th1-Th2 levels. The patient was treated with high dose methylprednisolone, 1 g day(-1) for 5 days (pulse therapy) followed by oral methylprednisolone 80 mg day(-1) for a week, tapered over 3 weeks. Within the first week of pulse therapy, she regained muscle strength of upper limbs against gravity. At the 2 year follow-up, MRI demonstrated obvious regression of the lesions in the medulla and cerebellum with disappearance of contrast enhancement. This case report is notable with the complete disappearance of MRI lesions at the 2 year follow-up after the treatment with high dose steroid.

Role of diffusion-weighted MR in differential diagnosis of intracranial cystic lesions.

AIM: The purpose of this study was to evaluate the role of diffusion-weighted imaging (DWI) in characterizing cerebral cystic lesions. The usefulness of the apparent diffusion coefficient (ADC) map in lesion characterization was also evaluated. METHODS: We compared the findings of conventional MR images with those of DWI: 63 cystic masses in 48 patients were examined with routine MR imaging and echo-planar DWI. The routine MR imaging included at least the axial T2- and T1-weighted sequences, and post-contrast T1 axial sequences. The DWI included an echo-planar spin-echo sequence with three values (0, 500 and 1000s/mm(2)) sensitizing gradient in the x, y, z direction, and it obtained an ADC map. RESULTS: The sensitivity of DWI for differentiating abscesses from primary brain tumours was 100%; for differentiating abscesses from metastatic tumours was 73%; for differentiating benign from malignant lesions was 90%. CONCLUSION: Although some metastatic lesions may appear hyperintense on DWI thus imitating an abscess, evaluation of the lesions with both DWI and conventional MRI may have an important contribution to the differentiation of tumours from abscesses.

Naloxone and lithium interaction on the levels of homovanillic acid in the rat brain.

The effects of long term (10 days) treatment of lithium and naloxone on HVA levels of striatum, hypothalamus and frontal cortex in rats were investigated. Lithium (400 mg/l in drinking water) itself had no effect on HVA levels of any region. Naloxone (2 mg/kg) treatment caused significant increases in the levels of HVA in hypothalamus and striatum and lithium cotreatment prevented the effect of naloxone. Neither of those were observed in the frontal cortical region.

Effect of naloxone on apomorphine-induced changes in locomotor activity of stress-exposed rats.

Acute and subacute effects of naloxone (10 mg/kg), apomorphine (0.125 mg/kg; 5 mg/kg) and stressful stimuli (immobilization, cold and sound) on locomotor activity were examined. In both acute and subacute (8 days) treatments, the lower dose of apomorphine decreased locomotor activity and the higher dose of apomorphine increased it. In the acute treatment, naloxone enhanced significantly the depressant effect of the lower dose of apomorphine on locomotor activity. Stress seemed to have no effect on apomorphine induced changes in locomotor activity of rats either in acute or in subacute treatment.

Musicogenic epilepsy with ictal single photon emission computed tomography (SPECT): could these cases contribute to our knowledge of music processing?

Musicogenic epilepsy has a strong correlation with the temporal lobe with a right-sided preponderance. We report the case of a 48-year-old woman whose seizures began at the age of 32 years. Her prenatal, natal and childhood histories were unremarkable and her family history was negative for epilepsy. She had typical complex partial seizures with chewing automatisms. Cranial computed tomography, magnetic resonance imaging (MRI) and interictal SPECT showed no abnormality. Interictal EEG showed paroxysmal bitemporal sharp wave discharges predominant on the right side. Ictal EEG showed a combination of high voltage sharp and slow sharp waves and spikes that originated from the right temporal leads and then became generalized. Ictal activity on EEG started 4-5 min after the music stimulus. For the ictal SPECT study, i.v. injection of 20 mCi of HMPAO was administered approximately 30 s after the ictal activity started. Ictal SPECT demonstrated a right anterior and mesial temporal hyperperfusion. These results seem to support the dominant role of the right temporal lobe and the possible relation of mesial temporal structures to the affective content of music in musicogenic epilepsy.

Effect of chronic administration of morphine on primary immune response in mice.

The effect of 3 different doses of chronically-administered morphine on the primary immune response was studied in mice by estimating spleen/body weight ratio and serum hemolysin production against sheep red blood cells (SRBC). It was observed that morphine exerted a dose-dependent inhibitory effect on the immune response which was antagonized by the concomitant administration of naloxone. The findings suggest that the inhibitory effect of morphine is specific.

Antagonizing effect of aspartic acid on the development of physical dependence on and tolerance to morphine in the rat.

As free amino acids in the brain have a role in the development of physical dependence on and tolerance to morphine, and in the mechanism of action of some drugs, the effects of aspartic acid which antagonizes some effects of the single dose of morphine were studied during the development of the physical dependence on morphine and after the withdrawal of morphine. 108 rats were given morphine and aspartic acid in different combinations in drinking water for 30 days. Every tenth day the dose of morphine was increased: At the end of this period some of them in each group continued or began to receive aspartic acid depending on the experimental conditions after the withdrawal of morphine. During the experiments body weight, spontaneous motor activity and analgesic threshold were determined. Aspartic acid prevented the alterations induced by morphine during the development of physical dependence and tolerance. Furthermore the rats that received aspartic acid after the withdrawal showed no body weight loss.