Pycnogenol® as an Adjunct in the Management of Childhood Asthma

A randomized, placebo-controlled, double-blind study involving 60 subjects, aged 6-18 years old, was conducted over a period of 3 months to determine the effect of Pycnogenol® (a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine) on mild-to-moderate asthma. After baseline evaluation, subjects were randomized into two groups to receive either Pycnogenol® or placebo. Subjects were instructed to record their peak expiratory flow with an Assess® Peak Flow Meter each evening. At the same time, symptoms, daily use of rescue inhalers (albuterol), and any changes in oral medications were also recorded. Urine samples were obtained from the subjects at the end of the run-in period, and at 1-, 2-, and 3-month visits. Urinary leukotriene C₄/D₄/E₄ was measured by an enzyme immunoassay. Compared with subjects taking placebo, the group who took Pycnogenol® had significantly more improvement in pulmonary functions and asthma symptoms. The Pycnogenol® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group. There was also a significant reduction of urinary leukotrienes in the Pycnogenol® group. The results of this study demonstrate the efficacy of Pycnogenol® as an adjunct in the management of mild-to-moderate childhood asthma.     

Synthesis of 14C‐labeled piperidines and application to synthesis of [14C]SCH 351125, a CCR5 receptor antagonist

1‐Benzyl‐4‐hydroxy[2‐¹⁴C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [¹⁴C]formaldehyde in high yield. The distribution pattern of ¹⁴C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [¹⁴C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐¹⁴C]piperidine in six steps. [¹⁴C]SCH 351125 is a mixture of four atropisomers. Preparation of [¹⁴C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd.     

Release of newly synthesized h-dopamine in the striatum: An adaptation of the push-pull cannula method to awake restrained and anesthetized rats

The release of newly synthesized ³H-dopamine (³H-DA) was measured in the rat striatum superfused, through a push-pull cannula, with a physiological medium enriched in ³H-tyrosine. The level of spontaneous ³H-DA release was dependent on the topographical localisation of the cannula in the striatum (anterior parts displayed higher levels than posterior ones) and on the anesthetic state (halothane anesthetized rats demonstrated higher levels than awake ones). Inhibition of DA inactivation processes by local application of benztropine (a DA reuptake inhibitor, 10⁻⁶ M) or by IV administration of pargyline (a MAO inhibitor, 100 mg/kg) enhanced the detectable outflow of ³H-DA from the striatum in both halothane anesthetized and awake rats. Local application of D-amphetamine (10⁻⁵ M) or acetylcholine (5 × 10⁻⁵ M) in the presence of eserine (5 × 10⁻⁵ M) evoked respectively a fivefold and a 30% increase in spontaneous ³H-DA release in halothane anesthetized rats. Inhibition of the firing of dopaminergic neurons by IV injection of gamma-hydroxybutyrate (400 mg/kg) produced a 30% decrease in striatal ³H-DA release. The present results demonstrate that the push-pull cannula method is suitable for the study of DA release in both the anesthetized and the awake rat.     

Single-shot ADC imaging for fMRI.

It has been suggested that apparent diffusion coefficient (ADC) contrast can be sensitive to cerebral blood flow (CBF) changes during brain activation. However, current ADC imaging techniques have an inherently low temporal resolution due to the requirement of multiple acquisitions with different b-factors, as well as potential confounds from cross talk between the deoxyhemoglobin-induced background gradients and the externally applied diffusion-weighting gradients. In this report a new method is proposed and implemented that addresses these two limitations. Specifically, a single-shot pulse sequence that sequentially acquires one gradient-echo (GRE) and two diffusion-weighted spin-echo (SE) images was developed. In addition, the diffusion-weighting gradient waveform was numerically optimized to null the cross terms with the deoxyhemoglobin-induced background gradients to fully isolate the effect of diffusion weighting from that of oxygenation-level changes. The experimental results show that this new single-shot method can acquire ADC maps with sufficient signal-to-noise ratio (SNR), and establish its practical utility in functional MRI (fMRI) to complement the blood oxygenation level-dependent (BOLD) technique and provide differential sensitivity for different vasculatures to better localize neural activity originating from the small vessels.     

Dilation of the ventriculus terminalis: sonographic findings.

A newborn term male infant was found to have the stigmata of VACTERL syndrome, including cervical and thoracic hemivertebra, partial sacral agenesis, 13 pairs of ribs, high imperforate anus with rectovesical fistula, and tracheoesophageal fistula with proximal esophageal atresia. No open spinal dysraphism or skin dimpling was seen. Ultrasonography of the spinal cord was performed to screen for occult anomalies. The examination revealed a lipoma of the filum terminalis and a low-lying conus medullaris at the L3-L4 level with a large central cystic structure in the terminal cord, which was continuous with the central canal (Fig. 1). This was thought to most likely represent a dilated ventriculus terminalis, and the diagnosis was confirmed on a subsequent MR image (Fig. 2). Fluid in the cyst followed cerebrospinal fluid signal in all sequences. We observed no abnormal signal in the adjacent parenchyma or enhancement associated with the cystic mass. A cranial ultrasonogram did not reveal any intracranial anomalies. The patient demonstrated no neurologic deficits in the lower extremities. Bowel and urinary continence was not assessable in this infant.     

Somatic von hippel-lindau mutation in clear cell papillary cystadenoma of the epididymis

Papillary cystadenoma of the epididymis is an uncommon benign lesion that may occur sporadically or as a manifestation of von Hippel—Lindau (VHL) disease. Neither immunohistochemical studies nor molecular genetic analyses of the VHL gene have been reported previously for this lesion. The authors describe two cases of clear cell papillary cystadenoma of the epididymis, both of which were initially confused with metastatic renal cell carcinoma. Both lesions showed positive immunohistochemical staining for low and intermediate molecular weight keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, α₁-antitrypsin, and α₁-antichymotrypsin. Each was negative for CEA. Because clear cell papillary cystadenoma is similar to renal cell carcinoma histologically, and because both occur as components of the von Hippel—Lindau disease complex, the authors analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL gene mutation was detected in one of the two tumors by polymerase chain reaction followed by single-strand conformation polymorphism analysis. Direct sequencing revealed a cytosine to thymine transition at nucleotide 694, resulting in the replacement of an arginine with a stop codon after the sixth amino acid of exon 3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene mutations may play a role in the initiation of tumorigenesis in sporadic cystadenomas of the epididymis.