Progression-directed therapy in patients with oligoprogressive castration-resistant prostate cancer.

PURPOSE: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. MATERIALS AND METHODS: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes. RESULTS: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. CONCLUSIONS: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

Quantification of IDP-73152, a novel antibiotic, in plasma from mice, rats and humans using an ultra-high performance liquid chromatography/tandem mass spectrometry method for use in pharmacokinetic studies.

IDP-73152, a novel inhibitor of a bacterial peptide deformylase, was recently approved as a new, investigational drug in Korea for the clinical management of infections caused by Gram positive bacteria. The objective of this study was to develop/validate a simple and robust analytical method for the determination of IDP-73152 in plasma samples from rodents and humans, and to assess the feasibility of the assay for use in pharmacokinetic studies using animal models. Plasma samples were processed using a standard method for protein precipitation and an aliquot of the extract then injected onto an UHPLC-MS/MS system. The drug and IDP-117293, an internal standard, were analyzed in the positive ion-mode by electrospray ionization and quantified by monitoring the transition at m/z 555.2→245.2 for IDP-73152 and 563.3→253.1 for the internal standard, respectively. The lower and upper limit of the assay was determined to be 5 and 10000ng/ml, respectively, with an acceptable linearity (R>0.999) in the response-concentration relationship. Validation parameters, including accuracy, precision, dilution, recovery, matrix effect and stability were found to be within the acceptable ranges recommended by the assay validation guidelines of the United States FDA. The method was successfully applied to the quantification of IDP-73152 in plasma from mice/rats that had received a single oral administration of 80mg/kg IDP-73152, in the form of the mesylate salt. These findings suggest that the validated assay can be used in preclinical and clinical pharmacokinetic studies of IDP-73152.

Changes in Neuroglial Activity in Multiple Spinal Segments after Caudal Epidural Pulsed Radiofrequency in a Rat Model of Lumbar Disc Herniation.

BACKGROUND: Herniated lumbar discs can induce sciatica by mechanical compression and/or chemical irritation. It was recently reported that neuroglial cellular activity after pulsed radiofrequency (PRF) application to a single dorsal root ganglion (DRG) attenuated neuroglial activity at the corresponding spinal dorsal horn. Recently, caudal epidural PRF has been used to manage neuropathic pain, but evidence of molecular changes after the administration of caudal epidural PRF to attenuate neuropathic pain is lacking, and it has not been determined whether caudal epidural PRF affects neuroglial activity at different spinal levels. OBJECTIVES: Using immunohistochemical methods in a rat model of lumbar disc herniation, the authors investigated the effects of caudal epidural PRF administration on pain-related behavior, on the activations of microglia and astrocytes in spinal cord, and on the expressions of calcitonin gene-related peptide (CGRP) and Transient receptor potential vanilloid 1(TRPV1) in the DRG at the L3, L4, L5, L6, and S1 levels. STUDY DESIGN: Controlled animal trial. SETTING: University hospital laboratory. METHODS: Forty-five Sprague-Dawley rats were randomly assigned to a sham-operated group (n = 10) or a nucleus pulposus (NP)-exposed group (n = 35). Rats in the NP-exposed group were further subdivided into a NP-exposed with sham stimulation group (the NP-nonPRF group; n = 13) or a NP exposed with caudal epidural PRF stimulation group (the NP-PRF group; n = 22). Pulsed radiofrequency was administered on postoperative day 10 (POD 10) by placing an electrode in the caudal epidural space through the sacral hiatus and administering 5 Hz of PRF current for 600 seconds (maximum tip temperature 42°C). Rats were tested for mechanical allodynia on POD 10 and on days 7 and 14 after caudal epidural PRF administration (post-PRF). At 14 days post-PRF, sections of the spinal cord from L3, L4, L5, L6, and S1 were immunostained for ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), and DRGs from the same levels were immunostained for CGRP and TRPV1. RESULTS: Mechanical withdrawal thresholds increased at 7 days post-PRF (P = 0.04), and the immunohistochemical expression of Iba1 in the L5 spinal dorsal horn and of CGRP in the L5 DRG were quantitatively reduced (P < 0.001) at 14 days post-PRF. Furthermore, the upregulations of Iba1 at L3, L4, L6, and S1 dorsal horns and CGRP at L6 DRG were also attenuated by caudal epidural PRF (P < 0.001). LIMITATION: We examined molecular changes only in ipsilateral lumbar regions and at 14 days post-PRF. CONCLUSION: Caudal epidural PRF reduced mechanical allodynia and downregulated microglia activity and CGRP expression at the lumbar disc herniated level and in adjacent lumbar spinal levels in a rat model of lumbar disc herniation.Key words: Caudal, pulsed radiofrequency, multisegmental, lumbar disc herniation, microglia, calcitonin gene-related peptide.

Identification of novel aminopiperidine derivatives for antibacterial activity against Gram-positive bacteria.

We have previously reported amidopiperidine derivatives as a novel peptide deformylase (PDF) inhibitor and evaluated its antibacterial activity against Gram-positive bacteria, but poor pharmacokinetic profiles have resulted in low efficacy in in vivo mouse models. In order to overcome these weaknesses, we newly synthesized aminopiperidine derivatives with remarkable antimicrobial properties and oral bioavailability, and also identified their in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP).

Formulation of a modified-release pregabalin tablet using hot-melt coating with glyceryl behenate.

A modified-release (MR) tablet of the anti-anxiety drug pregabalin (PRE) was prepared by hot-melt coating PRE with glyceryl behenate (GB) as a release retardant and compressing to form a matrix with microcrystalline cellulose (MCC) as a hydrophilic diluent. GB-coated PRE had a size in the range of 177-290 µm with good to acceptable flowability. Tablet hardness decreased slightly as GB content increased. PRE release from the tablet matrices was successfully modified by altering the ratio of MCC and GB, and it was found that dissolution- or diffusion-controlled release depended on the amount of GB used. Drug release was pH-independent. An accelerated stability test on the most promising MR tablet at 40°C and 75% relative humidity for 6 months showed no significant changes in PRE content, and the occurrence of total impurities--including PRE-lactam--was within acceptable limits. After oral administration of the selected MR tablet or a commercial IR capsule (Lyrica) to healthy human volunteers, pharmacokinetic parameters including Tmax, Cmax, AUC0-24, and T1/2 were compared. The confidence interval of AUC0-24 was within the adequate range, but that of Cmax was inadequate. This study demonstrated the potential use of GB for PRE-containing MR formulations.

Bioconversion of vitamin D3 to calcifediol by using resting cells of Pseudonocardia sp.

OBJECTIVES: Resting cells of Pseudonocardia sp. KCTC 1029BP were used for the bioconversion of vitamin D3 to calcifediol which is widely used to treat osteomalacia and is industrially produced by chemical synthesis. RESULTS: To obtain the maximum bioconversion yield of calcifediol by the microbial conversion of vitamin D3, a two-step optimization process was used, including the Plackett-Burman and the central composite designs. Six variables, namely agitation speed, aeration rate, resting cell concentration, vitamin D3 concentration, temperature, and pH, were monitored. Of these, aeration rate, resting cell concentration, and temperature were selected as key variables for calcifediol production and were optimized using the central composite design. Optimal bioconversion conditions obtained were as follows: aeration rate of 0.2 vvm, resting cell concentration of 4.7% w/v, and temperature of 33 °C. CONCLUSION: Using the optimal conditions, 356 mg calcifediol l(-1) was obtained with a bioconversion yield of 59.4% in a 75 l fermentor. These are the highest values reported to date.

Whole cell bioconversion of vitamin D3 to calcitriol using Pseudonocardia sp. KCTC 1029BP.

Calcitriol is an important drug used for treating osteoporosis, which can be produced from vitamin D3. The current method of producing calcitriol from vitamin D3 during cultivation of microbial cells results in low yields of calcitriol and high purification costs. Therefore, in this study, the steps of cell cultivation and bioconversion of vitamin D3 to calcitriol were separated. Cells of Pseudonocardia sp. KCTC 1029BP were utilized as a whole cell catalyst to produce a high level and yield of calcitriol from vitamin D3. In addition, the effects of bioconversion buffers, cyclodextrins, and metal salts on the production of calcitriol were comparatively examined and selected for incorporation in the bioconversion medium, and their compositions were statistically optimized. The optimal bioconversion medium was determined as consisting of 15 mM Trizma base, 25 mM sodium succinate, 2 mM MgSO4, 0.08% ß-cyclodextrin, 0.1% NaCl, 0.2% K2HPO4, and 0.03% MnCl2. Using this optimal bioconversion medium, 61.87 mg/L of calcitriol, corresponding to a 30.94% mass yield from vitamin D3, was produced in a 75-L fermentor after 9 days. This calcitriol yield was 3.6 times higher than that obtained using a bioconversion medium lacking ß-cyclodextrin, NaCl, K2HPO4, and MnCl2. In conclusion, utilizing whole cells of Pseudonocardia sp. KCTC 1029BP together with the optimal bioconversion medium markedly enhanced the production of calcitriol from vitamin D3.

Effects of Polygonatum sibiricum rhizome ethanol extract in high-fat diet-fed mice.

CONTEXT: The rhizome of Polygonatum sibiricum Redoute (Liliaceae) has long been used to treat diabetes-associated complications. However, the pharmacological mechanism of P. sibiricum on metabolic disorders is not clear. OBJECTIVE: This study investigates the effect of an ethanol extract of P. sibiricum rhizomes (designated ID1216) on obesity conditions including weight loss in high-fat (HF) diet-fed mice and explores the potential underlying mechanisms. METHODS: To identify the metabolic impact of the P. sibiricum rhizome extract, HF diet-fed mice were administered ID1216 orally at doses of 250 and 1000 mg/kg/d for 10 weeks, and various factors related to metabolic syndrome were analyzed. We also examined the effects of ID1216 on the expression of genes involved in adipogenesis and lipolysis in 3T3-L1 cells, as well as genes associated with energy homeostasis in C2C12 myocytes. RESULTS: ID1216 administration led to significant decreases in body weight gain (37.5%), lipid accumulation in adipose tissues (52.8%), and the levels of plasma triglycerides (26.4%) and free fatty acids (28.1%) at a dose of 250 mg/kg/d, compared with the vehicle-treated group, as well as improved insulin resistance. In addition, ID1216 was found to regulate the expression of genes related to adipogenesis and fatty acid oxidation in 3T3-L1 cells and enhance the expression of genes that modulate energy homeostasis in C2C12 myocytes. CONCLUSIONS: ID1216 may be a promising therapeutic agent for improving obesity conditions through the sirtuin-1 and peroxisome proliferator-activated receptor γ coactivator-1α pathway.

ID1201, the ethanolic extract of the fruit of Melia toosendan ameliorates impairments in spatial learning and reduces levels of amyloid beta in 5XFAD mice.

A previous study has demonstrated the anti-amyloidogenic effects of the ethanolic extract of Meliae Fructus (ID1201) using cell lines with stably expressed human Swedish mutant APP695 and ß-secretase 1, and 5Xfamilial AD (FAD) mice carrying five mutations. Here, we investigated the effects of ID1201 on cognitive impairment in 5XFAD mice. Daily administration of ID1201 was commenced at 3 months of age and continued for 3 months. Mice were serially trained in cued/response and place/spatial training tasks in the Morris water maze. After this training, testing for strategy preference was conducted. Non-transgenic control mice with vehicle treatment, vehicle-treated 5XFAD, and ID1201-treated 5XFAD mice showed equivalent performance in cued/response training. However, as training progressed to the subsequent place/spatial learning, vehicle-treated control and ID1201-treated 5XFAD mice differed significantly from vehicle-treated 5XFAD mice in measures of spatial learning (search error and adaptive spatial learning strategy). In the strategy preference test that followed, control mice preferred a place/spatial strategy relative to vehicle-treated 5XFAD mice, but differences between ID1201-treated 5XFAD mice and vehicle-treated 5XFAD mice were not significant. Additionally, ID1201 treatment reduced hippocampal levels of insoluble Aß42 and increased cortical levels of soluble amyloid precursor protein α. These results indicate that ID1201 may possess potential as a therapeutic agent for Alzheimer's disease by decreasing Aß deposits.

In vitro virucidal effect of mouthrinse containing C31G on seasonal influenza viruses.

C31G is a potent antimicrobial agent and can disrupt the microbial membrane by the alkyl portion of the molecule. The objective of this study was to evaluate the virucidal effectiveness of C31G and mouthrinse containing C31G (Sense-Time) on seasonal influenza viruses. Evaluation of the virucidal activity against influenza viruses was performed with end-point titration in 10-day-old chicken embryos and Madin-Darby canine kidney cells. In vitro studies demonstrated that C31G and Sense-Time inhibited the growth of seasonal influenza viruses even in the presence of 5% organic material. Gargling with C31G or Sense-Time would enhance oropharyngeal hygiene, which would be helpful for reducing influenza transmission.

Anti-amyloidogenic effects of ID1201, the ethanolic extract of the fruits of Melia toosendan, through activation of the phosphatidylinositol 3-kinase/Akt pathway.

Amyloid beta (Aß) peptides, which are generated from amyloid precursor protein (APP), are thought to play a major role in the pathogenesis of Alzheimer's disease (AD). This study investigated the anti-amyloidogenic effects of the ethanolic extract of Meliae Fructus (ID1201) using human embryonic kidney 293 cells with stably expressed human wild-type or Swedish mutant APP695 and ß-secretase 1. ID1201 treatment enhanced the non-amyloidogenic metabolism of APP; increases in soluble APPα levels and decreases in soluble APPß and Aß levels resulted from the α-secretase activation through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In addition, ID1201-treated 5×familial AD (FAD) mice with 5 mutations in APP and presenilin 1 showed reduced levels of Aß and amyloid plaques in the brain relative to those of 5×FAD mice with vehicle treatments. These results indicate that ID1201 possesses anti-amyloidogenic effects via the activation of the PI3K/Akt pathway, suggesting that it is a potential therapeutic agent for AD.

Optimization of medium components for high-molecular-weight hyaluronic acid production by Streptococcus sp. ID9102 via a statistical approach.

Hyaluronic acid (HA), linear high-molecular-weight glycosaminoglycan produced from Streptococcus sp., has raised interest in the medical and cosmetics industries because of the various biological functions of HA. In this paper, we report on the optimization of medium components for HA production in Streptococcus sp. ID9102 (KCTC 11935BP) by two-step optimization (one-factor-at-a-time and taguchi orthogonal array design). In the first step, medium components, such as carbon, nitrogen, phosphate, and mineral sources, were selected for HA production in Streptococcus sp. ID9102 (KCTC 11935BP) using the one-factor-at-a-time method. In the second step, the concentration of the selected medium components was optimized using taguchi orthogonal array design. The design for medium optimization was developed and analyzed using MINITAB 14 software. In addition, the effect of amino acid and organic acid, such as glutamine, glutamate, and oxalic acid, was studied for HA production in Streptococcus sp. ID9102 (KCTC 11935BP). Through these processes, the optimum medium comprising 4% glucose, 0.75% yeast extract, 1.0% casein peptone, 0.25% K(2)HPO(4), 0.05% MgCl(2), 0.5% NaCl, 0.04% glutamine, 0.06% glutamate, and 0.02% oxalic acid was determined. We were able to produce HA with a molecular weight of 5.9 x 10(6) at a productivity of 6.94 g/l on pilot scale fermentation.

Macular hole as a risk factor of choroidal detachment in rhegmatogenous retinal detachment.

PURPOSE: Choroidal detachment (CD) associated with rhegmatogenous retinal detachment (RRD) is a rare, but serious condition, which makes the prognosis worse. Previously reported risk factors for CD in RRD patients include high myopia, aphakia, pseudophakia, and advanced age. However, macular hole has not been discussed as an important factor in increasing the risk of CD in RRD patients. The purpose of this study was to evaluate macular hole as a risk factor for CD in eyes evidencing RRD. METHODS: The medical records of 480 patients with primary RRD were reviewed. We compared the CD incidence among the RRD patients in accordance with the presence or absence of macular holes. The relationship between gender, age, presence of systemic disease, refractive errors, lens status, intraocular pressure and the development of CD were also analyzed. RESULTS: The incidence (4/21 eyes, 19.0%) of CD in the RRD with macular hole was significantly higher than that (7/459 eyes, 1.5%) observed in the RRD without macular hole (p=0.010). The preoperative intraocular pressure (mean+/-SD; 2.5+/-1.3 mmHg) in the RRD with CD and macular hole was significantly lower than that (7.4+/-4.4 mmHg) observed in the cases of RRD with CD without macular hole (p=0.035). The eyes complicated by CD evidenced a higher prevalence of diabetes mellitus (p=0.024) than was observed in the eyes without CD. CONCLUSIONS: The retinal detachment combined with macular hole creates a predisposition toward the development of profound hypotony and CD.

Production of teicoplanin from Actinoplanes teichomyceticus ID9303 by adding proline.

We evaluated the influence of amino acids in improving teicoplanin productivity. Arginine, lysine, and proline were selected for better productivity among 20 amino acids in Erlenmeyer flasks. Proline was finally chosen as the additive for maximum teicoplanin productivity in a 5-liter fermenter. We obtained the highest teicoplanin productivity, 3.12 g/l, on the eighth d in a 75-liter pilot fermenter.

Induction of retinochoroidal venous anastomosis in central retinal vein occlusion with macular edema via a full-thickness retinochoroidal incision.

PURPOSE: To report the induction of retinochoroidal venous anastomosis (RCVA) in the treatment of nonischemic central retinal vein occlusion (CRVO) with macular edema via a full-thickness retinochoroidal incision. METHODS: In nine eyes with nonischemic CRVO and intractable macular edema, one or two full-thickness incisions transacting a major retinal branch vein to the level of inner sclera were made in conjunction with vitrectomy. Fluorescein angiography was conducted to evaluate the formation of functional RCVA. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after the surgery. RESULTS: The mean follow-up period +/- SD was 12.0 +/- 5.1 months. All nine eyes developed functional RCVA after the surgery. The mean BCVA +/- SD improved from 0.75 +/- 0.30 logMAR (logarithm of the minimal angle of resolution) to 0.55 +/- 0.26 logMAR (P = 0.018), and the mean CMT +/- SD was reduced from 686 +/- 265 microm to 251 +/- 150 microm (P = 0.011). Additional surgery was performed on one eye due to persistent vitreous hemorrhage. CONCLUSION: Full-thickness retinochoroidal incision appears to raise the rate of successful RCVA formation and may improve the outcome of CRVO with macular edema.

Retinal angiomatous proliferation and intravitreal bevacizumab injection.

PURPOSE: To evaluate the short-term efficacy and safety of intravitreal bevacizumab injection (IVBI) in patients with retinal angiomatous proliferation (RAP). METHODS: Seven eyes of 5 patients with RAP were included in this study. All of the eyes evidenced stage 2 RAP lesions, except for one eye with a stage 3 lesion. IVBI (1.25 mg/0.05 cc) were conducted at 4 or 6-week intervals. Complete ocular examinations, angiographic results and optical coherence tomographic findings before and after the IVBI were analyzed at baseline and upon the follow-up visits. RESULTS: Seven eyes were studied in 5 patients who had undergone IVBI. Partial (3 eyes) or complete (4 eyes) regression of RAP was noted after IVBI in all of the studied eyes. Visual acuity improved in 5 of the eyes, and was stable in 2 of the eyes. One eye evidenced severe intraocular inflammation after IVBI and a subsequent development of new RAP, which was controlled with vitrectomy and repeat IVBI. CONCLUSIONS: This treatment was effective over 6 months, stabilizing or improving visual acuity and reducing angiographic leakage. These short-term results suggest that IVBI may constitute a promising therapeutic option, particularly in the early stages of RAP.

Triple therapy of vitrectomy, intravitreal triamcinolone, and macular laser photocoagulation for intractable diabetic macular edema.

PURPOSE: To evaluate the effect of a sequentially combined triple therapy on intractable diabetic macular edema (DME). DESIGN: Prospective, interventional case series. METHODS: Twenty-four eyes from 24 subjects, diagnosed with intractable DME of nontractional origin, were subjected to vitrectomy. Intravitreal triamcinolone acetonide injection and macular laser photocoagulation were conducted sequentially at one and 14 days after vitrectomy. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were recorded before surgery and at three, six, and 12 months after triple therapy. RESULTS: The mean (+/- standard deviation [SD]) logarithm of the minimum angle of resolution BCVAs before and three, six, and 12 months after the triple therapy were 0.88 +/- 0.37, 0.55 +/- 0.33, 0.56 +/- 0.27, and 0.48 +/- 0.28, respectively. The mean (+/- SD) CMTs before and three, six, and 12 months after the triple therapy were 514 +/- 187 microm, 253 +/- 138 microm, 219 +/- 95 microm, and 197 +/- 91 microm, respectively. The changes in both BCVA and CMT at three, six, and 12 months from baseline were statistically significant (P < .003). The major adverse events after triple therapy were development of nuclear sclerotic cataracts (eight among 12 phakic eyes) and elevation of intraocular pressure (eight among 24 eyes). CONCLUSIONS: The triple therapy may facilitate early recovery of vision and may improve the long-term outcomes in some patients with DME refractory to conventional monotherapy.

Motor outcome according to diffusion tensor tractography findings in the early stage of intracerebral hemorrhage.

We tried to investigate the motor outcome according to diffusion tensor tractography (DTT) findings for the corticospinal tract (CST) in the early stage for hemiparetic patients with intracerebral hemorrhage (ICH). Forty patients with severe paralysis of the affected side were enrolled. DTT was obtained in the early stage of the stroke (7-30 days) and was classified into four groups: type A, the CST originating from primary motor cortex was preserved around the hematoma; type B, the CST was similar to type A except the fiber originated from the adjacent areas to the primary motor cortex; type C, the CST was interrupted at or around the hematoma; and type D, the CST did not reach the hematoma due to degeneration (Fig. 1). Six months after onset, motor function was measured and the statistical influence of the DTT type was tested. Initially, none of the motor function scales of the affected side differed among the four DTT types. Six months after the onset of ICH, motor functions of the same side were significantly different according to DTT type (p<0.05). All motor scales were highest in the DTT type A group, and were lowest in the DTT type D group (p<0.0003). The early DTT findings for CST may be used to predict the motor outcome of the affected extremities in hemiparetic patients with ICH.

Differences of cortical activation pattern between cortical and corona radiata infarct.

The aim of this study was to elucidate the differences of cortical activation pattern between patients with cortex (CO) infarct and those with corona radiata (CR) infarct. Twenty chronic patients with cerebral infarct and 11 normal subjects were recruited. The patients were classified into two groups according to infarct location: CO and CR group. After functional MRI was performed during the motor task of hand grasp-release movements, the hand motor function was assessed. The CO group tended to be activated on the contralateral primary sensori-motor cortex, whereas the CR group largely showed activation of the bilateral primary sensori-motor cortex. Namely, there was significantly more lateralized activation pattern of primary sensori-motor cortex in the CO group than in the CR group. Additionally, the CO group had better hand motor function than the CR group. Our results suggest that the motor recovery mechanism vary according to the lesion location between CO and CR infarct, indicating that the adaptive cortical reorganization proceeds under different patterns according to the lesion location.

Comparative QSAR studies on peptide deformylase inhibitors.

Comparative quantitative structure-activity relationship (QSAR) analyses of peptide deformylase (PDF) inhibitors were performed with a series of previously published (British Biotech Pharmaceuticals, Oxford, UK) reverse hydroxamate derivatives having antibacterial activity against Escherichia coli PDF, using 2D and 3D QSAR methods, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR). Statistically reliable models with good predictive power were generated from all three methods (CoMFA r (2) = 0.957, q (2) = 0.569; CoMSIA r (2) = 0.924, q (2) = 0.520; HQSAR r (2) = 0.860, q (2) = 0.578). The predictive capability of these models was validated by a set of compounds that were not included in the training set. The models based on CoMFA and CoMSIA gave satisfactory predictive r (2) values of 0.687 and 0.505, respectively. The model derived from the HQSAR method showed a low predictability of 0.178 for the test set. In this study, 3D prediction models showed better predictive power than 2D models for the test set. This might be because 3D information is more important in the case of datasets containing compounds with similar skeletons. Superimposition of CoMFA contour maps in the active site of the PDF crystal structure showed a meaningful correlation between receptor-ligand binding and biological activity. The final QSAR models, along with information gathered from 3D contour and 2D contribution maps, could be useful for the design of novel active inhibitors of PDF.