Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [³H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [³H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [³H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [³H]dopamine. Intravenous injections of [³H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [³H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.     

Effects of L-thyroxine suppressive therapy on cardiac mass in patients with differentiated thyroid cancer

Patients with differentiated thyroid carcinoma (DTC) receive a life time l-thyroxine therapy in suppressive doses and may exhibit signs of cardiac hypertrophy. The aim of the study was to analyze the left ventricle mass parameters by echocardiography in patients treated with suppressive doses of thyroxine and to relate them to the possible occurrence of cardiac arrhythmias. Ninety four patients aged 19-70 years treated chronically with l-thyroxine were randomly chosen from the population of patients with DTC without concomitant diseases of circulatory system. They were divided into two subgroups according to the length of thyroxine therapy (< 60 months and > or = 60 months). Control group consisted of 41 healthy volunteers, aged 22-73 years. Heart muscle dimensions were measured by echocardiography. Left ventricle mass (LVM) and mass index (LVMI) was calculated. Electrocardiography according to Holter was carried out in 57 patients. The results of echocardiography in the whole group of patients did not differ significantly from the control group, although a tendency towards higher dimensions of the left ventricle was observed. No correlation of hormonal parameters, or thyroxine dose, with LVM or results of Holters ecg was noted. When patients were subdivided into two groups, according to the duration of therapy, significantly higher values of LVM (215 +/- 64 g versus 186 +/- 55; p < 0.05) and LVMI (114 +/- 31 g/m versus 102 +/- 23 g/m; p < 0.05) were observed in patients treated > or = 60 months in comparison to the control group. When results of Holter's ecg in patients with increased LVMI were analyzed, cardiac rhythm disturbances were stated in 50% of them, but most were of minor clinical relevance. Suppressive l-thyroxine therapy does not induce significant left heart hypertrophy during the first 5 years of treatment. Patients treated through a longer period of time should be controlled by echocardiography because of the increasing risk of the left ventricle hypertrophy and arrhythmia.     

Effect of long-term administration of ranitidine,a histamine H2 receptor antagonist,on bone metabolism in young growing rats

Background

Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones.

Posttraumatic visual agnosia and epilepsy as a consequence of gunshot injury to the head. Case report

Half million people in the world, each year have a gunshot injury to the head and eighty thousand of them are hospitalized. Gunshot injuries to the head have became in Poland second most frequent cause of death from head trauma, and in some countries during peace became the most frequent cause of death among patient with head injury. Glasgow Coma Scale (GCS) is a useful prognostic factor for patients with gunshot injury to the head. Injury to the eloquent regions of the brain, commotion and contusion of the brain, intracranial hematomas, subarachnoid hemorrhage, cerebro-vascular spasm, injuries to the major vessels, liquorrhea, infections, coagulopathies and epilepsy are the most important and influential factors in the clinical status of the patient with gunshot injury to the head. The operation is the preferred treatment to all patient, no matter of their clinical status at the moment of the admission. The report presents the history of treatment of a patient with gunshot injury to the head. During the treatment extremely infrequently occurring posttraumatic visual agnosia and posttraumatic epilepsy were observed. Twenty-two months after operation the patient is independent and professionally active.     

Can sodium contents of foods be reduced by adding flavors? Studies with beef broth

Two experiments were conducted to investigate what effect the addition of spicy/herbal flavoring (allspice, marjoram, onion) and monosodium glutamate would have on the preferred level of saltiness in beef broth. First, subjects (N = 34) were asked to prepare ad lib mixtures according to their own preference of pairs of unsalted and salted broths: each pair was flavored with varying combinations of the four flavorants. Regardless of the flavor combination, the subsequent chemical analysis of mixtures indicated identical contents of NaCl (mean value 1.1% for all four combinations). Second, subjects (N = 38) rated the pleasantness of broths with 0.5, 0.8, 1.1, 1.4, and 1.7% NaCl under three sets of conditions: unflavored, flavored with allspice, majoram, onion and monosodium glutamate, and flavored with glutamate only. All samples but the one with a NaCl content of 0.5% were rated equally pleasant; the latter was rated somewhat less pleasant. The results provide no support for the widely held belief that other flavors, e.g., spices or herbs, might compensate for lower saltiness of foods.     

Legionella sp.--laboratory diagnosis of infections in humans and detection in environmental water]

Legionella sp. is the etiological agent of Legionnaires Disease and the Pontiac Fever, one of the new emerging diseases. Legionella are common in natural environment but in low number of bacteria cells, especially in comparison to other bacterial flora. Because of special nutritious requirement and long time of Legionella generation, the isolation of bacteria and the diagnosis of legionellosis cause many problems. In this publication some methods for detection of Legionella sp. in environmental water and clinical samples are presented and evaluated.     

Penile metastases from urogenital primaries

Metastatic tumors of the penis are rare. They are usually secondary to primaries of the genitourinary and gastrointestinal tracts. This entity is usually accompanied by distressing symptoms like dysuria, pain, induration, swelling of the penis and priapism, making immediate intervention necessary. Different methods of treatment are used to achieve the palliative effect: local surgical excision, penis amputation, radiotherapy or chemotherapy. Nevertheless, the prognosis is poor, because the disease is already disseminated and in most cases other metastases will occur soon.     

Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 10. Base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine

A series of base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine, a carbocyclic nucleoside, were synthesized and evaluated as inhibitors of S-adenosyl-L-methionine-dependent methyltransferases, including catechol O-methyltransferase, phenylethanolamine N-methyltransferase, and histamine N-methyltransferase. The base-modified analogues (8-azaadenine, 3-deazaadenine, and N6-methyladenine) were prepared by reaction of the corresponding carbocyclic 5'-chloro-5'-deoxynucleosides with the anion of homocysteine generated in situ either from L-homocystine or S-benzyl-L-homocysteine in Na/liquid NH3 or with DL-homocysteine thiolactone in alkaline solution. S-Aristeromycinyl-D-homocysteine was prepared with use of D-homocystine in the Na/liquid NH3 reaction. The sulfoxide and sulfone analogues were prepared by oxidation of S-aristeromycinyl-L-homocysteine. The various base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine were inactive as inhibitors of catechol O-methyltransferase. In contrast, the 3-deaza analogue was a good inhibitor (Ki = 20.5 +/- 1 microM) of phenylethanolamine N-methyltransferase whereas S-aristeromycinyl-D-homocysteine was an excellent inhibitor (Ki = 10.4 +/- 2.4 microM) of histamine N-methyltransferase. On the basis of these results, it would appear that the structural requirements for the binding S-aristeromycinyl-L-homocysteine are similar to those for binding S-adenosyl-L-homocysteine. Therefore, these carbocyclic analogues have the potential of being better inhibitors in vivo, because they should be more stable to metabolism than the ribosyl analogues.