Uniformity and Efficacy of Dry Powders Delivered to the Lungs of a Mycobacterial-Surrogate Rat Model of Tuberculosis

Pharmaceutical Research - Pulmonary administration of dry drug powder is a considered promising strategy in the treatment of various lung diseases such as tuberculosis and is more effective than...     

Different patterns of excitation and inhibition of the small hand and forearm muscles from magnetic brain stimulation in humans.

OBJECTIVES: The objective of the present study is to quantify the effects of voluntary muscle contraction of the small hand (abductor pollicis brevis, first dorsal interosseus (FDI)) and forearm muscles (extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), flexor carpi radialis (FCR) and flexor carpi ulnaris (FCU)) on motor evoked potentials (MEPs). METHODS: MEPs were recorded in 12 healthy subjects by a circular coil placed over the vertex at 1.2 times the resting motor threshold at different levels of the muscle contraction (0-100% of maximum voluntary contraction (MVC)). The effects of transcranial magnetic stimulation (TMS) on the onset latency, MEP area and silent period (SP) as a function of the %MVC were evaluated using a piecewise linear regression analysis. RESULTS: The MEP areas for the small hand muscles were almost completely saturated at 20% of MVC. In contrast, the MEP areas for radial muscles (ECR, FCR) had a dual increase at 40% of MVC while the ulnar muscles (ECU, FCU) had a dual increase at 20% of MVC. A uniform latency shift (1.5-3 ms reduction) was observed in all muscles with a changing point at 10% of MVC. The SPs were the longest for FDI and were not significantly influenced by MVC for any muscles. CONCLUSIONS: The excitatory and inhibitory effects of TMS on the MEPs differed for the small hand and forearm muscles and also between the ulnar and radial muscles. These results probably resulted from the different degrees of direct corticomotoneuronal inputs to each muscle and the inherent properties of the spinal motoneurons.     

Malignant astrocytoma of the conus medullaris treated by spinal cordectomy.

We present a case of malignant astrocytoma of the conus medullaris in a 48-year-old man treated by spinal cordectomy. Preoperative examination revealed a tumor at the T12 to L1 level, and intraparenchymal invasion up to T8. The spinal cord was amputated caudally to the root entry zones of the T9 sensory roots. Additional cordectomies were repeated three times because of tumor infiltration at the cut end. At each procedure, the cord was segmentally transected just caudal to the root entry zones of the p reserving-aid sensory roots to minimize the neural deficit. The final transected level was between T3 and T4, and the cut end did not pathologically reveal any tumor invasion. However, the patient died from tumor recurrence and dissemination. Although the attempt to control the tumor by long segment cordectomy was unsuccessful, spinal cordectomy with wide margin may be a possible treatment for patients with malignant astrocytoma of the conus medullaris presenting with complete deficit below the lesion a nd no dissemination, if in an early stage.     

Frequent mutations in Japanese patients with acid maltase deficiency

We screened 22 Japanese patients with acid maltase deficiency (seven with the infantile type, eight with the juvenile type and seven with the adult type) for three previously described mutations, D645E, S529V and R672Q, and a novel mutation, R600C. Although D645E has been reported to be common in Chinese patients with the infantile type, only three of 44 alleles (two of 14 infantile type alleles) from Japanese patients harbored the D645E mutation. The S529V mutation was identified in six of 14 alleles from adult-onset patients. None of the infantile or juvenile patients harbored the S529V mutation. Therefore, S529V apparently results in the adult type disease and is common in Japanese adult-onset patients. R672Q was identified in two pairs of siblings with the juvenile type. A novel mutation, R600C, was identified in eight of 22 patients (nine of 44 alleles). Therefore, R600C is another common Japanese mutation occurring at a CpG dinucleotide “hot spot”. Homozygosity for this mutation apparently results in the infantile phenotype. Genetic diagnosis by detecting these four mutations might be feasible for most Japanese patients with acid maltase deficiency.     

Suppressive effects of cyclosporin A and FK-506 on superoxide generation in human polymorphonuclear leukocytes primed by tumor necrosis factor alpha

Most previous studies have found no effects of cyclosporin A and FK-506 on active oxygen generation in human polymorphonuclear leukocytes. Recently various differences in biologic properties have been reported between unprimed peripheral blood human polymorphonuclear leukocytes and tissue or primed human polymorphonuclear leukocytes. In this study, we investigated the effects of cyclosporin A and FK-506 on superoxide (O(2)(-)) generation induced by the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine in human peripheral blood polymorphonuclear leukocytes primed or unprimed with tumor necrosis factor alpha. Neither cyclosporin A nor FK-506 suppressed N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced O(2)(-) generation in unprimed human polymorphonuclear leukocytes at concentrations between 0.1 nM and 10 microM, as in previous studies. Only at 1 microM of cyclosporin A and 100 nM of FK-506 were marginal suppressive effects observed. On the other hand, cyclosporin A and FK-506 both suppressed N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced O(2)(-) generation in tumor-necrosis-factor-alpha-primed human polymorphonuclear leukocytes, strongly and dose dependently, at concentrations between 1 nM and 1 microM. Neither cyclosporin A nor FK-506 influenced tyrosyl phosphorylation of 115 kDa protein, which is inducible during the priming process, suggesting that neither cyclosporin A nor FK-506 influenced the tumor-necrosis-factor-alpha-induced priming process itself, and instead modified the biologic response of primed human polymorphonuclear leukocytes.     

Fractional anisotropy and tumor cell density of the tumor core show positive correlation in diffusion tensor magnetic resonance imaging of malignant brain tumors

A noninvasive technique for assessing tumor tissue characteristics is required to assist preoperative surgical planning for malignant brain tumors. Preoperative information on tumor cell density within a tumor would help better define the target for tumor biopsy, resulting in more accurate diagnosis and grading of malignant brain tumors. One possible source of this information is diffusion tensor imaging (DTI), although to date studies have focused on its ability to delineate white matter fiber tracks by fiber-tracking and to detect tumor infiltration around the tumor and normal white matter interface. However, the use of DTI for providing information on cell density has also been examined, although with the controversial results. In addition the exact relationships between cell density and the two key values that DTI provides, namely fractional anisotropy (FA) and mean diffusivity (MD), still need to be investigated. In the present study we performed a retrospective investigation of tumor cell density and FA and MD values in biopsy cases. We found that FA has a good positive correlation (R=0.75) and MD has a good negative correlation (R=0.70) with tumor cell density within the tumor core. Similar correlation was observed between the Ki-67 labeling index and FA (R=0.71) and MD (R=0.62). Thus, measurement of both FA and MD within the tumor core has a potential to provide detailed information on tumor cell density within the tumor. Although data obtained from DTI should be interpreted carefully and comprehensively with other imaging modalities such as positron emission tomography, DTI seems to be informative for planning the best biopsy target containing the highest cell density.