Beneficial effect of Flos magnoliae extract on multiple low dose streptozotocin-induced type 1 diabetes development and cytokine-induced beta-cell damage

In the present study, Flos magnoliae extract (FME) was evaluated to determine if it could protect pancreatic beta-cells against multiple low dose streptozotocin (MLDS) and interleukin-1beta and interferon-gamma. Injection of mice with MLDS resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining. However, the induction of diabetes by MLDS was completely prevented when mice were pretreated with FME. FME also effectively protected beta-cells against cytokine toxicity, which was demonstrated by an increase in the viability of rat insulinoma RINm5F cells and by preserved insulin secreting responses to glucose in isolated rat islets. Moreover, cytokine-induced nitric oxide production and iNOS mRNA and protein expression were significantly reduced in RINm5F cells and islets that were preincubated with FME. The molecular mechanism by which FME inhibits iNOS gene expression in in vitro and in vivo appears to involve inhibition of NF-kappaB activation. Taken together, these results reveal the possible therapeutic value of FME for the prevention of type 1 diabetes progression.     

Protective effect of antioxidant supplementation in sperm-preparation medium against oxidative stress in human spermatozoa

BACKGROUND: Oxidative stress induced by reactive oxygen species (ROS) isassociated with an impaired fertilization ability of spermatozoa.We investigated the effects of adding antioxidants to a spermpreparation medium on the functional parameters of the spermatozoa. METHODS: Spermatozoa were washed with Ham's F-10 media containing theantioxidants, ethylenediaminetetraacetic acid (EDTA) and catalase,at various concentrations, and then the ROS levels in spermsuspensions, and the forward motility, acrosome reaction, DNAintegrity and lipid peroxidation of the spermatozoa were assessed. RESULTS: The ROS levels were significantly lower in sperm suspensionswashed with the antioxidants (196312 rlu; relative light units)than in control sperm (604 rlu, P < 0.05). The addition of10 µM EDTA to the sperm preparation medium significantlyimproved the motility of the spermatozoa compared with the controlgroup, the groups containing EDTA at other concentrations andthe groups containing catalase. Catalase significantly increasedthe acrosome reaction rate of the spermatozoa. Both EDTA andcatalase significantly decreased the DNA fragmentation rateof the spermatozoa. However, the antioxidants did not reducelipid peroxidation. CONCLUSIONS: Supplementing sperm preparation medium with EDTA or catalasesignificantly improved the overall functional parameters ofthe spermatozoa by reducing the ROS levels.     

Response preparation changes following practice of an asymmetrical bimanual movement

The purpose of the current study was to examine the effects of practice on the advance preparation of an asymmetrical bimanual movement. Participants performed 170 trials of a discrete bimanual aiming movement where the right arm moved twice the amplitude of the left, in response to an auditory “go” signal. During three of the first and last ten trials, the “go” signal was replaced with a startle (124 dB) stimulus, which is thought to trigger a prepared movement. Startle and non-startle (control) trials from early and late practice were compared on various kinematic and EMG measures. Results indicated that it is possible to pre-program a bimanual asymmetrical movement, and that advance preparation of movement amplitude changes with practice. Evidence was also provided that the different amplitude movements were performed using similar EMG timing between limbs, while adjusting the relative ratio of EMG amplitude. Furthermore, learning of the task appeared to be related to the ability to prepare the correct asymmetrical EMG amplitudes rather than changing the timing of the EMG pattern.     

Subconjuctival Loa loa with Calabar swelling

Loa loa is unique among the human filariae in that adult worms are occasionally visible during subconjunctival migration. A 29-yr-old African female student, living in Korea for the past 5 yr without ever visiting her home country, presented with acute eyelid swelling and a sensation of motion on the left eyeball. Her symptoms started one day earlier and became worse over time. Examination revealed a threadlike worm beneath the left upper bulbar conjunctiva with mild eyelid swelling as well as painless swelling of the right forearm. Upon exposure to slit-lamp illumination, a sudden movement of the worm toward the fornix was noted. After surgical extraction, parasitologic analysis confirmed the worm to be a female adult Loa loa with the vulva at the extreme anterior end. On blood smear, the microfilariae had characteristic features of Loa loa, including sheath and body nuclei up to the tip of the tail. The patient also showed eosinophilia (37%) measuring 4,100/microL. She took ivermectin (200 microg/kg) as a single dose and suffered from a mild fever and chills for one day. This patient, to the best of our knowledge, is the first case of subconjunctival loiasis with Calabar swelling in Korea.     

Nomograms for prediction of disease recurrence in patients with primary Ta, T1 transitional cell carcinoma of the bladder

We developed nomograms to predict disease recurrence in patients with Ta, T1 transitional cell carcinoma of the bladder. Thirty-eight training hospitals participated in this retrospective multicenter study. Between 1998 and 2002, a total of 1,587 patients with newly diagnosed non-muscle invasive bladder cancer were enrolled in this study. Patients with prior histories of bladder cancer, non-transitional cell carcinoma, or a follow-up duration of less than 12 months were excluded. With univariate and multivariate logistic regression analyses, we constructed nomograms to predict disease recurrence, and internal validation was performed using statistical techniques. Three-year and five-year recurrence-free rates were 64.3% and 55.3%, respectively. Multivariate analysis revealed that age (hazard ratio [HR]=1.437, p<0.001), tumor size (HR=1.328, p=0.001), multiplicity (HR=1.505, p<0.001), tumor grade (HR=1.347, p=0.007), concomitant carcinoma in situ (HR=1.611, p=0.007), and intravesical therapy (HR=0.681, p<0.001) were independent predictors for disease recurrence. Based on these prognostic factors, nomograms for the prediction of disease recurrence were developed. These nomograms can be used to predict the probability of disease recurrence in patients with newly diagnosed Ta, T1 transitional cell carcinoma of the bladder. They may be useful for patient counseling, clinical trial design, and patient follow-up planning.     

Selection of an affinity-matured antibody against a defined epitope by phage display of an immune antibody library

In a previous study, we generated a murine hepatitis B virus (HBV)-neutralizing monoclonal antibody (mAb), KR127, that binds to an epitope (amino acids 37-45, NSNNPDWDF) of the preS1 antigen. Furthermore, an epitope tag, S1 (NANNPDWDF), was developed for protein tagging. The aim of the present study was to develop a high-affinity antibody to the same preS1 epitope. Mice were immunized with the N-terminal domain of human thrombopoietin fused to the S1 tag (nTPO-S1), and a phage-displayed chimeric Fab library was constructed and screened by panning against nTPO-S1. A high-affinity antibody (3-34) was selected that binds to the preS1 antigen. The IgG molecules of 3-34 showed approximately nine-fold higher affinity (K(D) 1.2 nM) for preS1 compared with KR127 (K(D) 10.4 nM), competed with KR127 for binding to the epitope, and bound to HBV particles. This study provides a simple and efficient way to develop a high-affinity antibody to a defined epitope by phage display of an immune antibody library.     

Detecting neural-state transitions using hidden Markov models for motor cortical prostheses

Neural prosthetic interfaces use neural activity related to the planning and perimovement epochs of arm reaching to afford brain-directed control of external devices. Previous research has primarily centered on accurately decoding movement intention from either plan or perimovement activity, but has assumed that temporal boundaries between these epochs are known to the decoding system. In this work, we develop a technique to automatically differentiate between baseline, plan, and perimovement epochs of neural activity. Specifically, we use a generative model of neural activity to capture how neural activity varies between these three epochs. Our approach is based on a hidden Markov model (HMM), in which the latent variable (state) corresponds to the epoch of neural activity, coupled with a state-dependent Poisson firing model. Using an HMM, we demonstrate that the time of transition from baseline to plan epochs, a transition in neural activity that is not accompanied by any external behavior changes, can be detected using a threshold on the a posteriori HMM state probabilities. Following detection of the plan epoch, we show that the intended target of a center-out movement can be detected about as accurately as that by a maximum-likelihood estimator using a window of known plan activity. In addition, we demonstrate that our HMM can detect transitions in neural activity corresponding to targets not found in training data. Thus the HMM technique for automatically detecting transitions between epochs of neural activity enables prosthetic interfaces that can operate autonomously.     

Familial Hemiplegic Migraine with Prolonged Coma and Cerebellar Atrophy: CACNA1A T666M Mutation in a Korean Family

We report the first Korean patient with familial hemiplegic migraine type 1, with clinical and multimodal imaging findings. A 43-yr-old man was admitted for right hemianopia and aphasia, followed by coma. MRI showed only cerebellar atrophy. CT angiography showed mild vasodilation of intracranial blood vessels and increased vascularity in the left hemisphere and perfusion-weighted imaging showed elevated cerebral blood flow. Gene analysis of the patient and his mother led to the identification of a heterozygous point mutation (1997C→T, T666M) in exon 16 of the CACNA1A gene. Familial hemiplegic migraine should be considered in patients with episodic neurological dysfunction with cerebellar atrophy.     

Central anti-diabetic action of biguanide and thizolidinediones in d-glucose fed and streptozotocin-treated mouse models

Background

In the present study, the possible anti-diabetic action of biguanide and thiazolidinediones administered supraspinally or spinally was studied in ICR mice.

Methods

Mice were intracerebroventricular (i.c.v.) or intrathecal (i.t.) treated with 20 or 30 μg metformin, pioglitazone and rosiglitazone in d-glucose fed and streptozotocin-treated models, and blood glucose levels was measured at 30, 60 and 120 min after i.c.v. or i.t. administration.

Results

We found that i.c.v. injection with metformin or rosiglitazone slightly attenuated the blood glucose level in d-glucose fed model, whereas pioglitazone showed no effect on the blood glucose level in d-glucose fed model. The i.t. administration with metformin, pioglitazone or rosiglitazone did not alter the blood glucose level in d-glucose fed model. We also assessed the possible roles of biguanide and thiazolidinedione in the regulation of the blood glucose level in streptozotocin-treated model. We found in the present study that i.c.v. or i.t. administration with metformin caused a pronounced attenuation of the blood glucose level in streptozotocin-treated model. However, rosiglitazone administered i.c.v. did not affect the blood glucose level in streptozotocin-treated model.

Conclusions

Our results suggest that the anti-diabetic actions of metformin and rosiglitazone appear to be mediated via the brain regions as revealed in d-glucose fed animal model. Furthermore, metformin administered supraspinally or spinally may be effective for treating type I diabetes mellitus as revealed in streptozotocin-treated mouse model.