Pharmacological evidence, using in vivo dialysis, that substances additional to ascorbic acid, uric acid and homovanillic acid contribute to the voltammetric signals obtained in unrestrained rats from chronically implanted carbon paste electrodes

In vivo voltammetry at chronically implanted carbon paste electrodes in unrestrained rats is a particularly useful technique for evaluating neurochemical changes during spontaneous behaviour, or behaviour under experimental control. A 3 peak signal is observed in the striatum; most recently the consensus view has attributed these peaks to ascorbic acid (AA), uric acid (UA) and homovanillic acid (HVA) in ascending order of oxidation potential. We have used a pharmacological approach, combined with in vivo dialysis, to further elucidate the nature of the contributing species. Allopurinol, an inhibitor of xanthine oxidase, and thus of uric acid production, has previously been reported to abolish peak 2. We now report, using dialysis, that it selectively depletes UA in the extracellular fluid (ECF). Pargyline, a monoamine oxidase inhibitor, reduces peak 3 transiently (max. 60%) as expected, however it results in a more sustained reduction in ECF HVA (max. 100%). It also increases peak 1 (max. 75%) and decreases peak 2 (max. 40%), although changes in ECF AA and UA measured by dialysis and HPLC are minimal. Pargyline does however reduce ECF 5-hydroxyindoleacetic acid by 65%. We conclude that, using linear sweep voltammetry at chronically implanted paste electrodes: (a) one or more substances in addition to AA can contribute to peak 1; dopamine can do so in some situations; (b) 5-hydroxyindoleacetic acid, as well as UA, contributes to peak 2; its contribution is about one third that of the latter; and (c) one or more substances in addition to HVA can contribute to peak 3. 3-Methoxytyramine can do so. Since this is another methylated metabolite of dopamine, this does not prevent the use of peak 3 as an index of dopamine metabolism, and may extend its usefulness to situations where monoamine oxidase is inhibited.     

Cyclosporin-A nephrotoxicity and acute cellular rejection in renal transplant recipients: correlation between radionuclide and histologic findings

Serial radionuclide studies using both Tc-99m DTPA (perfusion) and I-131 hippuran (tubular function) were correlated with histologic findings in 25 patients with renal transplants. These cases included 15 cases of cyclosporin-A nephrotoxicity (CsA-NT) and ten cases of acute cellular rejection that were retrospectively selected on the basis of biopsy findings and favorable clinical response to therapy specific for each of these conditions. The serial radionuclide studies enabled the correct diagnosis in 12 of 15 cases of CsA-NT and eight of ten cases of acute rejection. Posttherapy radionuclide studies, furthermore, demonstrated improvement consistent with clinical response. In all cases, the radionuclide results were available at least 24 hours before biopsy findings. These results indicate that serial radionuclide studies evaluating interval changes in both perfusion and tubular function are of significant value in the diagnosis and follow-up of CsA-NT and acute cellular rejection in transplant recipients. This initial experience suggests a sensitivity of 80%.     

Polymorphonuclear leucocyte motility in patients with severe burns

Chemotaxis, chemokinesis and cellular orientation were measured for unstimulated and 10(-7) n-formyl methionyl leucyl phenylalanine (F-met-leu-phe) stimulated polymorphonuclear leucocytes (PMNS) of nine patients with recent 10-80 per cent burns using a computer-assisted image analysis technique. The technique records PMN movement, as viewed with a phase-contrast microscope on videotapes, and then uses computer programs to calculate the speed and direction of up to 50 PMNS over a 5-min period. Orientation was determined visually. Cellular adherence was also measured by attachment methods. PMNS from burn patients were slower (av. speed 16.8 microns/min), responded less well to F-met-leu-phe (av. speed 20.9 microns/min, av. McCutcheon index 0.32), were less often oriented towards the chemoattractant (av. 39 per cent) and were more adherent (av. 50 per cent) than control cells (av. speed 21.8 microns/min; av. speed F-met-leu-phe 32.2 microns/min; McCutcheon index 0.61; oriented 59 per cent adherent; 16 per cent). Thus PMNS from burn patients orient less well, are significantly slower and have less directionality in response to a chemoattractant, and are more adherent suggesting activation.     

Idiopathic hypereosinophilic syndrome terminating as disseminated T-cell lymphoma

The authors describe a case of idiopathic hypereosinophilic syndrome (HES) terminated as a T-cell lymphoma in a 3-year-old girl. The clinical course was chronic and characterized by chronic eczema, persistent peripheral blood eosinophilia, organomegaly, interstitial lung change, and pericarditis. Postmortem examination demonstrated a disseminated T-cell lymphoma involving the inguinal lymph node, liver, lung, and kidney. The findings of the current case suggest a possibility that certain abnormalities in this case of idiopathic HES per se may have triggered the development of malignant lymphoma, and it may represent a transition of idiopathic HES into a T-cell lymphoma. Other possible sequences are discussed. The development of T-cell malignancy in idiopathic HES in a girl is quite an unusual presentation.     

Mitigation of hearing loss from semi-circular canal transection in pseudomonas otitis media with ciprofloxacin-dexamethasone irrigation.

HYPOTHESIS: Irrigation of the mastoid with a quinolone antibiotic-steroid solution may mitigate hearing loss caused by iatrogenic semicircular canal injury in the presence of Pseudomonas aeruginosa (PA) otitis media (OM). BACKGROUND: Studies have shown the cochlea to be more vulnerable to semicircular canal transection (SCT)-related hearing loss in the presence of PA OM. Prophylactic systemic antibiotics and steroids may decrease this hearing loss, but SCT is usually not planned. The aim of this study was to determine if irrigation with ciprofloxacin-dexamethasone (cipro-dex) could improve hearing outcomes following SCT in PA OM. METHODS: PA OM was induced in 28 animals. After three to five days, unilateral SCT was performed in each animal, with sham SCT on the contralateral ear. At surgery, half of the animals (n = 14) underwent irrigation of the both mastoid bullae with cipro-dex; the second group of animals (n = 14) underwent irrigation of the bullae with sterile saline. Auditory thresholds were obtained immediately prior to SCT and 7-10 days after SCT. RESULTS: SCT ears treated with cipro-dex showed a mean click threshold improvement of 4.6 dB from pre-transection to 7-10 days post-transection, whereas thresholds in the SCT ears treated with saline worsened by 7.5 dB (p = 0.15). CONCLUSION: Irrigation of the guinea pig bulla with cipro-dex following SCT in the setting of PA OM appears safe and may yield beneficial effects on hearing.     

Cultural perspectives and current consumption changes of cooked rice in Korean diet

Cooked rice is a staple food for Koreans which provides more than 60% of daily required energy. In 1960''s, Koreans ate 600 g-800 g of cooked rice per meal and the energy obtained from cooked rice was almost more than 80% of the daily intake of energy. However, as the economy of Korea improved, the major industry has been shifted from agriculture to various manufacturing industries and the export of those products has been increased thus increasing the national income but decreasing the farming population and thus rice consumption have been decreased. It has been said that the decreased rice consumption is caused solely by decreased farming population but it can also be said that the decreased farming population is caused by decreased rice consumption.As the national income increases, the type of foods people consume have become diversified. Various processed foods such as convenience food or ready-to-eat food have been widespread, which are mostly made of wheat flour rather than rice.     

Localization of dystonic muscles with 18F-FDG PET/CT in idiopathic cervical dystonia.

The purpose of this study was to investigate whether (18)F-FDG PET/CT is useful for localizing dystonic cervical muscles in patients with idiopathic cervical dystonia (ICD) by comparing disease severity before and disease severity after botulinum toxin (BT) injection into hypermetabolic muscles. METHODS: Six patients with ICD underwent (18)F-FDG PET/CT. Dystonic muscles suitable for BT injection therapy were defined as those showing diffusely increased (18)F-FDG uptake. RESULTS: Hypermetabolic cervical muscles were identified in all 6 patients. In 2 patients who underwent PET/CT both in a supine position and in a sitting position during (18)F-FDG uptake, abnormal hypermetabolic muscles were observed by PET/CT only when patients were in the sitting position with their heads and necks in the adopted abnormal involuntary posture. Symptoms were significantly improved in 4 patients who underwent BT injection therapy guided by PET/CT and who were clinically monitored. CONCLUSION: (18)F-FDG PET/CT is potentially useful for identifying dystonic cervical muscles for BT therapy in patients with ICD.     

Spontaneous disappearance of a suprasellar arachnoid cyst: case report and review of the literature

Introduction Suprasellar arachnoid cysts are uncommon developmental anomalies that are most often diagnosed in childhood. Because the natural history and pathogenesis of these remain poorly defined, optimal treatment guidelines are not yet established.Case report We report a case of spontaneous disappearance of a suprasellar arachnoid cyst that persisted after a ventriculoperitoneal shunt performed 10 years earlier. A 5-year-old boy presented with impaired visual acuity and urinary incontinence. Magnetic resonance (MR) imaging showed a large suprasellar cyst with noncommunicating hydrocephalus. A ventriculoperitoneal shunt was put in place to alleviate current aggravation of hydrocephalus symptoms. Because of the persistent size of the cyst and signs of brainstem compression on a repeat computed tomography (CT), we recommended surgical exploration and decompression. However, the boy’s parents declined any further surgical treatment, and the patient was subsequently lost to follow-up for 10 years. When the patient returned to our clinic at the age of 15 years, a repeat MR scan showed a complete disappearance of the cyst. His family denied any significant interval history.Discussion This case represents only the third reported case of spontaneous disappearance of a suprasellar arachnoid cyst. We discuss possible mechanisms and clinical characteristics of the disappearance of the arachnoid cyst with review of the literature.     

Blockade of LTB4-induced chemotaxis by bioactive molecules interfering with the BLT2-Gαi interaction

BLT2, a low-affinity leukotriene B₄ (LTB₄) receptor, is a member of the G-protein coupled receptor (GPCR) family and is involved in the pathogenesis of inflammatory diseases such as asthma. Despite its clinical implications, however, no pharmacological inhibitors are available. In the present study, we screened for small molecules that interfere with the interaction between the third intracellular loop region of BLT2 (BLT2_iL3) and the Gα_i3 protein subunit (Gα_i3), using a high-throughput screening (HTS) assay with a library of 1040 FDA-approved drugs and bioactive compounds. We identified two small molecules—purpurin [1,2,4-trihydroxy-9,10-anthraquinone; IC₅₀ = 1.6 μM for BLT2] and chloranil [tetrachloro-1,4-benzoquinone; IC₅₀ = 0.42 μM for BLT2]—as specific BLT2-blocking agents. We found that blockade of the BLT2_iL3-Gα_i3 interaction by these small molecules inhibited the BLT2-downstream signaling cascade. For example, BLT2-signaling to phosphoinositide-3 kinase (PI3K)/Akt phosphorylation was completely abolished by these molecules. Furthermore, we observed that these small molecules blocked LTB₄-induced chemotaxis by inhibiting the BLT2-PI3K/Akt-downstream, Rac1-reactive oxygen species-dependent pathway. Taken together, our results show that purpurin and chloranil interfere with the interaction between BLT2_iL3 and Gα_i3 and thus block the biological functions of BLT2 (e.g., chemotaxis). The present findings suggest a potential application of purpurin and chloranil as pharmacological therapeutic agents against BLT2-associated inflammatory human diseases.