Rathke cleft cyst: MR and biomedical analysis of cyst content

PURPOSE: At least one type of Rathke cleft cyst has unique MR findings, specifically, high intensity on T1-weighted images and iso- to low intensity on T2-weighted images relative to white matter. To clarify the influence of cyst content on MR images, we analyzed the cyst content by biomedical methods after surgical removal. METHOD: We studied five patients diagnosed with Rathke cleft cyst, whose MR images showed high intensity on T1-weighted images and iso- to low intensity on T2-weighted images. After surgery, total protein and cholesterol levels were quantified, and correlations of protein and cholesterol content with T1 and T2 signal intensities were performed in vitro. RESULTS: All five cysts had very high concentrations of protein (11,700-26,600 mg/dl, mean 17,940 mg/dl) with nearly no cholesterol (at most 2.0 mg/dl). Along with increases in protein concentration in vitro, the signal intensity of T1-weighted images increased, while that of T2-weighted images decreased. In contrast, the cholesterol concentration sequence influenced the signal intensity of neither T1- nor T2-weighted images. CONCLUSION: The unique MR finding of Rathke cleft cysts--high signal intensity on T1-weighted images and low signal intensity on T2-weighted images--might depend mainly on protein concentration, not on cholesterol.     

Double muscle transfer for upper extremity reconstruction following complete avulsion of the brachial plexus

Recent interest in reconstruction of the upper limb following brachial plexus injuries has focused on the restoration of prehension following complete avulsion of the brachial plexus. The authors use free muscle transfers for reconstruction of the upper limb to resolve the difficult problems in complete avulsion of the brachial plexus. This article describes the authors' updated technique--the double free muscle procedure. Reconstruction of prehension to achieve independent voluntary finger and elbow flexion and extension by the use of double free muscle and multiple nerve transfers following complete avulsion of the brachial plexus (nerve roots C5 to T1) is presented. The procedure involves transferring the first free muscle, neurotized by the spinal accessory nerve for elbow flexion and finger extension, a second free muscle transfer reinnervated by the fifth and sixth intercostal nerves for finger flexion, and neurotization of the triceps brachii via its motor nerve by the third and fourth intercostal motor nerves to extend and stabilize the elbow. Restoration of hand sensibility is obtained via the suturing of sensory rami from the intercostal nerves to the median nerve. Secondary reconstruction, including arthrodesis of the carpometacarpal joint of the thumb and glenohumeral joint, and tenolysis of the transferred muscle and distal tendons, improve the functional outcome. Based on the long-term result, selection of the patient, donor muscle, and donor motor nerve were indicated. Most patients were able to achieve prehensile functions such as holding a can and lifting a heavy box. This double free muscle transfer has provided prehension for patients with complete avulsion of the brachial plexus and has given them new hope to be able to use their otherwise useless limbs.     

Serosurvey of wild rodents for Rickettsioses (spotted fever, murine typhus and Q fever) in Java Island, Indonesia

The prevalence of antibodies against spotted fever group rickettsia (SFGR), murine typhus and Q fever were investigated in wild rats captured in Indonesia. Sera of 327 rats were collected from Jakarta and Boyolali on Java Island. The prevalences of antibodies against SFGR and murine typhus were 128 (39.1%) and 48 (14.7%), respectively. Antibodies against Q fever were not detected in these serum samples. Antibodies against SFGR were found in all species of rats (20.8–51.9%). The antibody positive rate against murine typhus in Rattus norvegicus (38.0%) was significantly higher than that in other rat species (0–4.8%, p < 0.01). The antibody positive rates against SFGR and murine typhus in rats captured in Jakarta were significantly higher than those in rats captured in Boyolali (p < 0.01). In this survey, all species of rats had antibodies against SFGR, indicating that the 4 species of tested rats (R. norvegicus, R. rattus, R. exulans, R. tiomanicus) were infected with SFGR and that SFGR may infest the whole of Java Island. Most of the rats that were antibody-positive against murine typhus were captured in Jakarta. Therefore, R. norvegicus and R. rattus are likely to be important hosts of murine typhus in Jakarta. The antibody-positive rates against SFGR and murine typhus in rats captured in the dry season were significantly higher than those in rats captured in the rainy season. This may coincide with the active periods of ticks and fleas in Indonesia.     

Interaction of the new histamine H2-receptor antagonist pibutidine hydrochloride with canine cloned H2-receptor expressed cells

The effect of a new histamine H2-receptor antagonist, pibutidine hydrochloride ((Z)-3-amino-4-{4-{4-[(piperidinomethyl)pyrid-2-yl]oxy} but-2-enylamino}cyclobut-3-ene-1,2-dione monohydrochloride, CAS 126463-66-9, IT-066 displaced the binding of [3H]tiotidine to cells transfected with the wild-type H2-receptor in a concentration-dependent manner. Compared with the 50% inhibitory concentration values (IC50) among five H2-receptor antagonists tested, the value of IT-066 was lowest. The inhibitory effect of IT-066 was enhanced by preincubation of IT-066 with the cells, and preincubation for 60 min increased potency about 2-fold. Famotidine also has such effects. When H2-receptor transfected cells were treated with IT-066 for 30 min, the inhibitory effect of IT-066 on the [3H]tiotidine binding still remained even after the cells were extensively washed. Scatchard plot analysis supported the non-competitive and irreversible action of IT-066. When the canine mutated H2-receptor-expressed cells were used, which have substituted amino acid of 190Alanine (Ala; position: 190th amino acid) for 190Threonine (Thr) in the fifth transmembrane domain, IT-066 also inhibited [3H]tiotidine binding to the cells concentration-dependently. However, in the case of the 190Ala mutated cells, the inhibitory effect of IT-066 attenuated with a decrease in maximal response after washing of the cells. These results show that IT-066 could tightly bind H2-receptor in a time-dependent manner and suggest the possibility that the irreversible inhibition of IT-066 is important in the interaction with 190Thr in the fifth transmembrane domain of H2-receptor.     

Microphysiometric analysis of human alpha1a-adrenoceptor expressed in Chinese hamster ovary cells.

1. The human recombinant alpha1a-adrenoceptor (AR) has been stably expressed in Chinese hamster ovary cells. Four stable clones, aH4, aH5, aH6 and aH7, expressing 30, 370, 940 and 2900 fmol AR mg(-1) protein, respectively, have been employed to characterize this AR subtype using radioligand binding and microphysiometry to measure extracellular acidification rates. 2. Noradrenaline (NA) gave concentration-dependent responses in microphysiometry with increasing extracellular acidification rates. The potency of NA increased as the receptor density increased; pEC50 values of NA for the clones aH4, aH5, aH6 and aH7 were 6.9, 7.5, 7.8 and 8.1, respectively. This increase of potency according to receptor density indicates the presence of spare receptor for NA. Methoxamine, phenylephrine, oxymetazoline and clonidine also gave concentration-dependent responses with various intrinsic activities. 3. Antagonists shifted concentration-response curves for NA rightward in a concentration-dependent manner. Schild analysis revealed that the affinity profile of this AR subtype to antagonists in the clone aH7 had a typical pattern for the alpha1a-AR; high affinity for prazosin and WB 4101, and low affinity for BMY7378 (pA2=9.5, 9.8 and 7.3, respectively). This profile is similar in the case of the clone aH4. These affinities were in good agreement with those obtained in binding experiments. 4. These results have demonstrated that (1) classical receptor theory can be applied in microphysiometry, and (2) microphysiometry is a useful tool to investigate the pharmacological characterization of alpha1a-AR.     

Delayed administration of ethyl eicosapentate improves local cerebral blood flow and metabolism without affecting infarct volumes in the rat focal ischemic model.

The objective of this study was to assess whether delayed administration of ethyl eicosapentate has a favorable effect on cerebral blood flow and metabolism in rats suffering from cerebral infarction. Adult male Sprague-Dawley rats weighing 250-300 g were used. Left middle cerebral artery occlusion was induced for 2 h. After 24-h reperfusion, rats were treated with ethyl eicosapentate (100 mg kg(-1); ethyl eicosapentate treated) or saline (saline treated) by gavage, once a day for 4 weeks. After 4 weeks, local cerebral blood flow and local cerebral glucose utilization were measured autoradiographically, and infarction size was measured. In the ischemic side, the local cerebral blood flow and local cerebral glucose utilization values in the parietal cortex and the lateral caudoputamen, which constituted the ischemic core, were equivalent to zero in both groups. The peri-infarcted areas, i.e., the frontal cortex and medial caudoputamen, were significantly higher in the ethyl eicosapentate treated group than the saline treated group. In the non-ischemic side, ethyl eicosapentate treated group had a tendency to improve local cerebral blood flow and local cerebral glucose utilization values in a medial caudoputamen. These results suggest that ethyl eicosapentate treatment may be beneficial for maintaining cerebral circulation and metabolism except for infarction area after cerebral infarction.     

Identification of binding sites of bopindolol and its two metabolites with beta1-adrenoceptors by molecular modeling: comparison with beta2 adrenoceptors

This study was designed to examine the importance of interaction in the bindings of nonselective beta-blockers to beta1-adrenoceptors (beta1-ARs) as compared with beta2-ARs, using molecular modeling. The beta-blockers used in this study were bopindolol [4-(benzoyloxy-3-t- butylaminopropyl)-2-methylindol hydrogen malomate], its two metabolites [18-502 - hydrolyzed bopindolol or 4-(3-t-butylamino-2-hydroxypropoxy)-2-methyl indole - and 20-785 - 4-(3-t-butylaminopropoxy)-2-carboxyl indole], and propranolol. Molecular modeling was performed on an Indigo2 workstation (Silicon Graphic) using Discover/Insight II (Molecular Simulations) software. Through molecular modeling, possible binding sites for these drugs were suggested to lie between helices 3, 4, 5, and 6 of the beta1-AR. The amine, benzoic acid, indole methyl, t-butyl, phenyl, and indole functional groups of bopindolol possibly interact with Asp138 (transmembrane - TM - 3), Ser190 (TM 4), Ala343 (TM 6), Val137 (TM 3), Pro339 (TM6), Cys336 (TM 4), Leu237 (TM 5), and Pro236 (TM 5) of beta1-AR, respectively, by either hydrogen bonding or hydrophobic interactions. In addition, 18-502, 20-785, and propranolol also interacted with sites at the same positions as those of beta2-ARs. Thus, the results of the present study suggested that although Ala343 and Val137 of beta1-AR among these amino acids were different from those of beta2-AR, the interactions at the same sites between ligands and amino acids of beta1-AR as those of beta2-ARs may occur because these drugs are nonselective.     

Morphine-induced changes in cyclic AMP metabolism and protein kinase activity in the brain.

The effects of consecutive oral administration of morphine on the cyclic AMP synthesizing system and cyclic AMP dependent protein kinase activity in the cerebral cortex of mice were examined. The administration of morphine (2--4 weeks) induced an increase of the cyclic AMP formation by activating adenylate cyclase, whereas responses of the cyclic AMP synthesizing system to biogenic amines (norepinephrine, dopamine and histamine) added in vitro was found to be significantly attenuated in these animals. Cyclic AMP dependent protein kinase activity in the cerebral cortex was also increased following a consecutive oral administration of morphine. These changes in the activities of adenylate cyclase and protein kinase were found mainly in crude mitochondrial and/or synaptosomal fractions. Morphine induced decrease in the response of the cyclic AMP synthesizing system to biogenic amines was rapidly reversed, and a significant increase of the cyclic AMP formation in the presence of added norepinephrine compared with that found in morphinized animals was observed following the administration of levallorphan, a narcotic antagonist. On the other hand, the changes in adenylate cyclase and cyclic AMP dependent protein kinase activities were not affected significantly by levallorphan administration. These results suggest that alterations in activities of cyclic AMP synthesizing system and of cyclic AMP dependent protein kinase may be involved in processes of the formation of morphine dependence. Possible involvement of abrupt increments in the sensitivity of "norepinephrine receptor-adenylate cyclase" system and a subsequent increase in cerebral cyclic AMP is also suggested as a cause of morphine withdrawal syndrome.