New iridoids from Asperula maximowiczii

Three new dimeric iridoid glucosides, named asperuloides A (1), B (2), and C (3), were isolated from Asperula maximowiczii, along with the known compound picconioside II. The structures of the new compounds were determined by spectroscopic and chemical methods and by the single-crystal X-ray diffraction analysis of 1.     

Novel cognitive improving and neuroprotective activities of Polygala tenuifolia Willdenow extract,BT-11

We carried out this study to search a new active constituent that had cognitive enhancing activity and low side effects from natural source. We found that the extract of dried root of Polygala tenuifolia Willdenow (BT-11, 10 mg/kg, i.p.) could significantly reverse scopolamine-induced cognitive impairments in rat, using a passive avoidance and a water maze test. We also investigated the effects of BT-11 on neurotoxicity induced by glutamate (Glu) and toxic metabolites of amyloid precursor protein (APP) such as amyloid beta protein (A beta) and C-terminal fragment of APP (CT) in primary cultured neurons of rat. The pretreatment of BT-11 (0.5, 3, and 5 micro g/ml) significantly reduced cell death induced by Glu (1 mM), A beta (10 micro M) and CT105 (10 micro M) in a dose-dependent manner. In addition, BT-11 inhibited acetylcholinesterase (AChE) activity in a dose-dependent and non-competitive manner (IC(50) value; 263.7 micro g/ml). Our novel findings suggest the possibility that this extract may have some protective effects against neuronal death and cognitive impairments in Alzheimer's disease (AD), or other neurodegenerative diseases related to excitotoxicity and central cholinergic dysfunction.     

Intraocular properties of hexadecyloxypropyl-cyclic-cidofovir in Guinea pigs.

OBJECTIVE: We previously reported a long-lasting crystalline lipid pro-drug of cyclic cidofovir, hexadecyloxypropyl-cyclic-cidofovir (HDP-cCDV), to treat experimental retinitis in rabbit eyes. With HDP-cCDV there was a longer intraocular therapeutic effect than with cidofovir (CDV) and no toxicity with 100 microg/eye. It has been known that CDV and related analogues lower intraocular pressure (IOP) after local use, and it is also accepted that the guinea pig is a better model to study this toxicity before human clinical trials. METHODS: HDP-cCDV was intravitreally injected into 10 guinea pig eyes in doses of 4, 9, and 18 microg in 20 microL/eye. An 18-microg quantity is the dose equivalent to 100 microg/eye in the rabbit. Only one eye of each animal received drug and the fellow eye served as the control. After injection, the eyes were monitored with tonometry, ophthalmoscopy, electroretinography (ERG), and histology. RESULTS: Intravitreal injections of doses of 18 microg/eye or lower revealed no toxicity and a high therapeutic index (132,000 to 3300 times higher than the 50% effective concentration for human cytomegalovirus) during 10 weeks of observation. The crystalline drug depot was ophthalmoscopically visible in the inferior vitreous cavity for 5-10 weeks. There was no difference in IOP between the drug-injected and control eyes at any time points (P > 0.05) except for day 3 after drug injection (P = 0.0338). All eyes demonstrated a normal ERG waveform with no differences between the treated and the fellow control eyes (P = 0.85). Histology revealed normal morphology and structures of the retina and ciliary body in all eyes (with or without treatment). CONCLUSION: Crystalline HDP-cCDV may be a long-lasting and safer alternative to cidofovir to treat CMV retinitis without the retinal or ciliary body toxicity observed with CDV.     

Randomized trial of influenza vaccine with granulocyte-macrophage colony-stimulating factor or placebo in cancer patients.

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) would improve response to influenza vaccination in cancer patients. PATIENTS AND METHODS: In a randomized, patient-blinded, placebo-controlled trial carried out in 1997 to 2000, 133 patients were stratified into five groups of treatment and disease. Single doses of standard split trivalent influenza vaccine and either placebo or 250 micro g of GM-CSF were administered at the same time. Hemagglutination inhibition assay titers were measured before and 4 weeks after vaccination. RESULTS: Standard analyses, which define response as at least a four-fold increase in titers, detect no effect of GM-CSF for any of the three influenza subtypes in the trivalent vaccines (P >or=.12). Analysis that includes the magnitude of the change in titers and combines responses of the subtypes suggests that the placebo group had the greater response (P =.051), thus indicating that GM-CSF does not improve response. Ancillary analyses show that response declines both with increasing age and with higher initial titers. The fraction of patients with at least a four-fold increase in titers was 0.36 (95% confidence interval, 0.29 to 0.42) CONCLUSION: A single 250- micro g dose of GM-CSF administered with the influenza vaccine does not improve response to vaccination. Response in cancer patients is low and declines as age and initial titer increase.     

Perfusion MR Imaging in Gliomas: Comparison with Histologic Tumor Grade

Objective

To determine the usefulness of perfusion MR imaging in assessing the histologic grade of cerebral gliomas.

Materials and Methods

In order to determine relative cerebral blood volume (rCBV), 22 patients with pathologically proven gliomas (9 glioblastomas, 9 anaplastic gliomas and 4 low-grade gliomas) underwent dynamic contrast-enhanced T2*-weighted and conventional T1- and T2-weighted imaging. rCBV maps were obtained by fitting a gamma-variate function to the contrast material concentration versus time curve. rCBV ratios between tumor and normal white matter (maximum rCBV of tumor / rCBV of contralateral white matter) were calculated and compared between glioblastomas, anaplastic gliomas and low-grade gliomas.

Results

Mean rCBV ratios were 4.90°±1.01 for glioblastomas, 3.97°±0.56 for anaplastic gliomas and 1.75°±1.51 for low-grade gliomas, and were thus significantly different; p < .05 between glioblastomas and anaplastic gliomas, p < .05 between anaplastic gliomas and low-grade gliomas, p < .01 between glioblastomas and low-grade gliomas. The rCBV ratio cutoff value which permitted discrimination between high-grade (glioblastomas and anaplastic gliomas) and low-grade gliomas was 2.60, and the sensitivity and specificity of this value were 100% and 75%, respectively.

Conclusion

Perfusion MR imaging is a useful and reliable technique for estimating the histologic grade of gliomas.     

Intermittent Therapy for Melasma in Asian Patients with Combined Topical Agents (Retinoic Acid,Hydroquinone and Hydrocortisone): Clinical and Histological Studies

Melasma is a common problem in Asians, but treatments have not been satisfactory. In the present study, we evaluated the efficacy of a new formula containing 0.1% tretinoin, 5% hydroquinone, and 1 % hydrocortisone (RHQ) in Korean patients with melasma. Twenty-five Korean females with therapy recalcitrant melasma applied RHQ on their faces for 4 months and were evaluated before and 4 weeks after treatment clinically and histologically. They were also evaluated clinically 4 months after treatment. To minimize unavoidable side effects (erythema or peeling), we applied RHQ twice a week instead of the usual daily application. However, we obtained clinical and histological results comparable to other reports from white populations. Statistically significant depigmentation in clinical and histological studies and increased subepidermal collagen synthesis were observed in this study. These effects were seen as early as 4 weeks after treatment with RHQ. We used mMASI scoring, a modified version of the original MASI, to quantify the effects of RHQ more objectively and easily.     

Colorectal anastomotic strictures: treatment by fluoroscopic double balloon dilation

PURPOSE: To evaluate the therapeutic efficacy and complications of fluoroscopically guided double balloon dilation for treatment of colorectal anastomotic strictures. MATERIALS AND METHODS: Under fluoroscopic guidance, 17 patients with colorectal anastomotic strictures underwent transanal double balloon dilation. Thirteen of 17 strictures were the consequence of surgery for malignant disease and the other four were secondary to surgery for benign disease. Sixteen of 17 patients had difficult or frequent defecation caused by partial obstruction. In the remaining one asymptomatic patient, the stricture was detected by endoscopy and barium enema after total proctocolectomy and a temporary ileostomy for ulcerative colitis. The therapeutic efficacy and complications were evaluated during the follow-up. RESULTS: Seventeen patients underwent double balloon dilation in a single session. The diameter of the first balloon was 20 mm and the second balloon's diameter was 10, 15, or 20 mm. Technical success was achieved in all 17 patients. After balloon dilation, complete (n = 12, 71%) or incomplete (n = 5, 29%) improvement of symptoms was achieved in all patients. Major complications such as perforation or severe hemorrhage did not occur. During the mean follow-up period of 23 months (range, 1-62 months), one patient (6%) developed a recurrent stricture and required a second session of double balloon dilation 6 months after initial balloon dilation. CONCLUSION: Fluoroscopically guided double balloon dilation is an effective and safe method for the treatment of colorectal anastomotic strictures.     

Benign duodenal strictures: treatment by means of fluoroscopically guided balloon dilation

Fluoroscopically guided balloon (15 or 20 mm in diameter) dilation was performed on eight patients with benign duodenal strictures caused by peptic ulcers (n = 6), Crohn's disease (n = 1), and postoperative adhesion (n = 1). The procedure was technically and clinically successful without complications in seven of the eight patients (88%). Duodenal perforation occurred immediately after 20-mm-diameter balloon dilation in one patient who underwent emergency surgery. During the mean follow-up of 30 months (range, 2-103 months), there was recurrence in two of the seven patients (29%) who then underwent surgery. The other five patients (71%) showed good results with no recurrence.     

Results of temporary placement of covered retrievable expandable nitinol stents for tuberculous bronchial strictures

Covered retrievable expandable nitinol stents were successfully placed in nine patients with tuberculous bronchial strictures refractory to balloon dilation. Complications included stent migration (n = 1) and tissue hyperplasia at the proximal portion of the stent (n = 2). During the follow-up period (5-52 months), stricture recurred in three of five patients (60%) after temporary stent placement for 2 months, whereas stricture did not recur in the other four patients after temporary stent placement for 6 months. Temporary placement of covered retrievable stents appears to be an effective method for the treatment of patients with tuberculous bronchial strictures refractory to balloon dilation.     

Fixation Methods for Implantable Port Chamber: Comparative Study Using Glue, Self-stabilizing Leg and Suture Fixations in Rabbits

Objective

To evaluate the fixation strength and tissue reaction of the glue fixation and self-stabilizing leg fixation methods and to compare the results with those of the conventional tagging suture fixation method.

Materials and Methods

Twelve healthy rabbits were selected and three different methods of implanting the port chamber were employed on the back of each rabbit. A total of thirty six port chambers were implanted with these three different methods, viz. the glue fixation method using tissue adhesive, the self-stabilizing leg method using a self-expandable stabilizing leg, and the suture fixation method. The fixation strength and the gross and histopathologic changes of each fixation method were evaluated at three days, one week, two weeks and four weeks after port implantation.

Results

The glue fixation method showed a good fixation strength, which was similar to that of the tagging suture method (p = 0.3486). Five of the six ports (83%) implanted with the glue fixation method which were examined after two weeks showed cracks on the external surface, but this had no adverse effects on their function. A large amount of granulation tissue reaction was found at the bottom of the chamber (p = 0.0025). The fixation with the self-stabilizing leg showed relatively lower fixation strength (p = 0.0043), but no turning-over of the chamber occurred. The fixation strength improved with time after the first week, and minimal granulation tissue reaction was observed with this method.

Conclusion

The glue fixation method exhibited equal fixation strength compared to the suture fixation, but showed cracking and a large amount of granulation tissue, whereas the fixation with a self-stabilizing leg showed weaker fixation strength.