Recombinant human growth hormone (rhGH) administration stimulate the secretion of the brain insulin-like growth factor-1 (IGF-1) concentration and IGF-1 is a pleiotropic neurotropic peptide to exert beneficial effect for the injured brain tissues. Citicoline (cytidine-59-diphosphocholine; CDP-choline) is well known to improve neurological outcome in acute stroke. This study aimed to evaluate whether rhGH can potentiate citicoline effect on functional recovery in acute stroke patient. Thirty patients were enrolled. Ten patients were treated with rhGH subcutaneous injection for 6 months on top of citicoline for 6 weeks (GH6 group), and 10 patients for 3 months (GH3 group) with 6 weeks of citicoline treatment as well, and final 10 patients only with citicoline (control group). Functional outcome was determined by Korean modified Barthel Index (K-MBI) and modified Rankin Scale (mRS) at baseline and 6 months after treatment. Seven and 4 patients withdrew from GH6 and GH3 group, respectively. Final 3 patients in GH6 group, 6 patients in GH3 group and 10 patients in control group were analyzed. The K-MBI, and mRS scores from all 3 groups increased in 6 months compared to baseline in intra-group comparison. In inter-group comparison, however, GH6 but not GH3 showed statistically significant improvement compared to control. Administration of rhGH for 6 months on top of 6-week citicoline treatment resulted in further improvement in K-MBI and mRS in acute stroke patients. Further studies in increasing injection dose or injection period is needed.
Brain ; Cytidine Diphosphate Choline ; Human Growth Hormone* ; Humans* ; Injections, Subcutaneous ; Insulin-Like Growth Factor I ; Stroke*

BACKGROUND AND PURPOSE: Cerebral white matter (WM) lesions are frequently observed in human cerebrovascular diseases, and are believed to be responsible for cognitive impairment. Various neuroprotective agents can suppress this type of WM or neuronal damage. In this study, we investigated whether citicoline, a drug used to treat acute ischemic stroke, can attenuate WM lesions and cognitive decline caused by chronic hypoperfusion in the rat. METHODS: Animals were divided into immediate- and delayed-treatment groups. Those in the immediate-treatment group received a sham operation, citicoline (500 mg/kg/day), or phosphate buffered saline (PBS) treatment. Citicoline or PBS was administered intraperitoneally for 21 days after occluding the bilateral common carotid arteries. Rats in the delayed-treatment group were intraperitoneally administered with either 500 mg/kg/day citicoline or PBS for 21 days beginning on the 8th day after the operation. From the 17th day of administration, the rats were placed in an eight-arm radial maze to examine their cognitive abilities. After completing the administration, tissues were isolated for Kluver-Barrera and the terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) staining. RESULTS: In the immediate-treatment group, cognitive functions were preserved in the citicoline-treated group, and WM damage and TUNEL-positive cells differed significantly between the citicoline- and PBS-treated animals. In the delayed-treatment group, there was no decrease in WM damage and TUNEL-positive cells, but cognitive improvement was evident for citicoline treatment relative to PBS treatment. CONCLUSIONS: These results show that citicoline can prevent WM damage and aid cognitive improvement, even after a certain extent of disease progression. Citicoline might be useful in patients with acute ischemic stroke as well as in chronic stroke accompanied with cognitive impairment.
Animals ; Carotid Artery, Common ; Cytidine Diphosphate Choline ; Disease Progression ; DNA Nucleotidylexotransferase ; Humans ; Neurons ; Neuroprotective Agents ; Rats ; Salicylamides ; Stroke

OBJECTIVE: To examine the correlation between Berg balance scale (BBS) which is tool for assessing the clinical balance function and sensory organization test (SOT) of computerized dynamic posturography (CDP) in brain injured patients. METHOD: Thirty patients with brain injury were assessed on the BBS and SOT of CDP. BBS consists of 14 items and each item is graded on a five point ordinal scale (0~4), yielding a total of 56 points. According to its characteristics, each item was divided 3 groups, which were sitting, standing and position change. Six equilibrium scores (EQ) were determined by SOT of CDP (EquiTest System , Version 5.08) under 6 conditions, and somatosensory, visual, vestibular ratios were analyzed by 6 EQ scores. RESULTS: EQ 5 was correlated with reaching forward item (r=0.513), turning 360 degrees item (r=0.537), stool stepping item (r=0.529) of BBS (p<0.01). EQ 6 was correlated with turning 360 degrees item (r=0.498) of BBS (p<0.01). Sum of standing item group scores was correlated with EQ 5 (r=0.478), EQ 6 (r=0.464), and sum of position change item scores was correlated with EQ 5 (r=0.622), EQ 6 (r=0.514) (p<0.01). Vestibular ratio was correlated with BBS total score (r=0.552, p<0.01). CONCLUSION: We concluded that vestibular ratio of SOT was correlated with BBS, especially position change item group. Therefore BBS is a good tool for evaluating vestibular function in brain injured patients.
Brain Injuries ; Brain* ; Cytidine Diphosphate ; Humans

PURPOSE: To examine whether citicoline has a neuroprotective effect on kainic acid (KA) -induced retinal damage. METHODS: KA (6 nmol) was injected into the vitreous of rat eyes. Citicoline (500mg/kg, i.p.) was administered to the rats once before and twice a day after KA-injection for 3- and 7-day intervals. The neuroprotective effects of citicoline were estimated by measuring the thickness of the various retinal layers using hematoxylin-eosin (H and E) staining. In addition, immunohistochemistry was conducted to elucidate the expression of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS). RESULTS: Morphometric analysis of retinal damage in KA-injected eyes showed significant cell loss in the inner nuclear layer (INL) and inner plexiform layer (IPL) of the retinas at 3 and 7 days after KA injection, but not in the outer nuclear layer (ONL). At 3 days after citicoline treatment, no significant changes were detected in the retinal thickness and immunoreactivities of eNOS and nNOS. The immunoreactivities of eNOS and nNOS increased in the retina at 7 days after the KA injection. However, prolonged treatment for 7 days significantly attenuated the immunoreactivities and the reduction of thickness. CONCLUSIONS: The results indicate that citicoline has a neuroprotective effect on KA-induced neurotoxicity in the retina.
Retina/*drug effects/*pathology ; Rats, Sprague-Dawley ; Rats ; Neurotoxins/*pharmacology ; Neuroprotective Agents/*pharmacology ; Male ; Kainic Acid/*pharmacology ; Cytidine Diphosphate Choline/*pharmacology ; Animals

OBJECTIVETo assess the clinical efficacy of the therapeutic schema for treatment of diabetic peripheral neuropathy (DPN) with ligustrazine and citicoline injection in combination.

METHODSAdopting double-centered randomized controlled trial, 300 patients were randomly assigned to 3 groups, who were treated respectively by ligustrazine plus citicoline (group A), ligustrazine alone (group B) and citicoline alone (group C). Clinical efficacy, symptomatic integral (SI), electromyogram ( EMG), blood sugar and blood lipids were assessed 4 weeks after treatment, and the clinical efficacy and SI were assessed at the end of 3-month follow-up.

RESULTSAfter 4-week treatment, improvements of blood sugar and blood lipids were seen in all the three groups, showing insignificant difference among them (P > 0.05). But the clinical efficacy, improvement of SI and EMG in group A were superior to those in group B and C (P < 0.05), while the difference between group B and C was insignificant. No severe adverse reaction was found. Results at the end of 3-month follow-up showed that the clinical efficacy in group A was still better than in the other two groups, so did the SI (6.39 +/- 2.04 vs 8.36 +/- 1.17 and 8.05 +/- 1.34, P < 0.05).

CONCLUSIONThe therapeutic schema of using ligustrazine and citicoline in combination is effective and safe for improving DPN, and worthy of clinical spreading.

Adolescent ; Adult ; Aged ; Cytidine Diphosphate Choline ; therapeutic use ; Diabetic Neuropathies ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Young Adult

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.
Rats ; Animals ; Periploca ; Cysteine ; Cytidine Diphosphate Choline ; Network Pharmacology ; Phosphorylcholine ; Metabolomics ; Arthritis, Rheumatoid/drug therapy* ; Biomarkers ; Glycerophospholipids ; Methionine ; Purines ; Chromatography, High Pressure Liquid

OBJECTIVE: To study normal values of wnwry organimtion test(SOT) and motor control test(MCT) of computerized dynamic posturography(CDP) in the healthy Koreans. BACKGROUND: Balance is made up of three biological functions ; sensory input, motor output, and CNS integration. But, there has been no method for assessing the sensory, motor, and CNS integration function quantitatively. CDP is a tool for assessing the balance function quantitatively under a variety of tasks. METHODS: To assess the balance using CDP, I studied equilibrium score(ES) of SOT and weight symmetry, latency, and adaptation seems of MCT in 112 Korean healthy population. Arbitarily I divided the population into two groups, under 60 years and over 60 years of age. In SOT, I studied the contribution of each sense to maintaining equilibrium when other senses were either absent or provided with inaccurate information. MCT provoked autonomic postural reactions through a series of sudden anterior and posterior support surface translations. In MCT, I studied latencies in sudden translation of fact plate. RESULTS: The study group was 112 Korean healthy population with a mean age of 47 +/- 26 years. In SOT, the range of median equilibrium seems were from 68 to 93 under 60 years group, 58 to 91 over 60 years group. In MCT, during sudden anterior and posterior pertubation, weight symmetries were 101 +/- 24.8 under 60 years group and 104 + 30. 1 over 60 years group. Median latencies were 116 to 141msec under 60 years, 127 to 130msec over 60 down test of MCT the mean adaptation scores were 60 years. 64 to 75 and 48 to 73 over 60 years, respectively. CONCLUSION: This study could be a baseline control data in sensory, motor, and CNS integration function of balance in dizziness patient using CDP.
Cytidine Diphosphate ; Dizziness ; Humans ; Posture* ; Reference Values ; Translations

OBJECTIVES: The Korean College of Neuropsychopharmacology and the Korean Academy of Schizophrenia developed the Korean medication algorithm project for schizophrenia (KMAP) to aid clinical decisions. The purpose of this study was to investigate problems and revision of Korean Medication Algorithm for Schizophrenia after feasibility test. METHODS: A total of 108 schizophrenia patients were enrolled at 19 centers and treated according to the algorithm. Prescribing investigators were able to change the recommended treatment strategies of the algorithm if necessary. All subjects were assessed over a 4-month period. Appropriateness of choice, dosage, duration and switch of antipsychotics and definition of treatment response were examined. RESULTS: Compliance of 1(st) choice antipsychotics in KMAP was favorable. Atypical antipsychotics which is a 1(st) stage drug selected first was above 84%, especially in case of no previous medical history was nearly all. In case that shift of stage was needed, there is a trend that combination treatment stage (6(th) stage) and clozapine treatment stage (5(th) stage) were preferred to rather than 3(rd) stage and 4(th) stage (typical antipsychotics and atypical antipsychotics treatment stage). The rates of switching antipsychotics at the time points other than CDP (critical decision points) was low and the reason was almost the side effects. So the compliance of CDPs in KMAP was good in case of insufficiency of treatment response. Also the reasons why many investigators continued using current antipsychotics without switching despite insufficiency of treatment response were definition of treatment response, discrepancy between brief symptom rating scale for negative symptom and decision of clinicians. In addition, compliance of co-existence symptoms and side effect of medication in KMAP was favorable. CONCLUSION: It is some difference from clinical practice such as stage of antipsychotics, definition of treatment response and usefulness of brief symptom rating scale for negative symptom. But the majority apart from points of preceding paragraph is feasible in clinical practice. These results are essential to revise the next version of KMAP.
Antipsychotic Agents ; Clozapine ; Compliance ; Cytidine Diphosphate ; Humans ; Research Personnel ; Schizophrenia

BACKGROUND: The purpose of this study was to quantitatively assess the subclinical balance dysfunction in elderly people taking antiepileptic drugs. METHODS: We recruited sixty-three patients who were at least 50 years old, without complaint of dizziness or imbalance, and on a stable dose of carbamazepine, lamotrigine or levetiracetam. Their balance scores were compared with those of newly diagnosed untreated age- and sex-matched epilepsy patients (n=21). All the subjects underwent balance measurements that included an activities-specific balance confidence scale, quantitative caloric and rotational chair testing and posturography. The spectral frequency analysis of body sway while standing upright was also investigated. Sensory organization (SOT) and motor control tests were done by computerized dynamic posturography (CDP). RESULTS: The sway distance and area of center of pressure significantly increased in the patients treated with carbamazepine. Spectral frequency analysis of this group showed a significantly increased spectral power at low and middle frequencies on the antero-posterior (Y) plane and at low frequencies on the lateral (X) plane. CDP showed no significant differences in SOT results among the groups. However, motor control test revealed increased latencies and slowed adaptations in the carbamazepine group. CONCLUSIONS: These findings suggest that newer drugs such as lamotrigine or levetiracetam may induce less disequilibrium than carbamazepine in older people on monotherapy for epilepsy. The disturbance is likely related to slowed central postural reflexes.
Aged ; Anticonvulsants ; Carbamazepine ; Cytidine Diphosphate ; Dizziness ; Epilepsy ; Humans ; Piracetam ; Triazines

OBJECTIVETo investigate the effects of citicoline on spatial learning and memory of rats after focal cerebral ischemia.

METHODSThe rats were randomly divided into sham-operation group, ischemia control group and citicoline group. In the later two groups, focal cerebral ischemia model was established by introducing an intraluminal filament into the left middle cerebral artery, and citicoline (500 mg/kg) or 0.9% NaCl was administered intraperitoneally once a day for 2 weeks after the operation. The rats in the sham-operation group were not subjected to middle cerebral artery occlusion (MCAO) with intraluminal filament. The spatial learning and memory functions of the rats were evaluated by Morris water maze test 15 days after MCAO for 5 days.

RESULTSThe rats in ischemia control group exhibited serious spatial learning and memory deficits in both place navigation test and spatial probe test. In the former test, the mean escape latency of citicoline-treated rats were significantly shorter than that of ischemia control rats (P<0.01), and in the latter test significant diffidence was noted between citicoline and ischemia control groups in the percentage time spent in the former platform quadrant and frequency of crossing the former platform (P<0.05).

CONCLUSIONCiticoline can improve the spatial learning and memory function of rats after focal cerebral ischemia.

Animals ; Avoidance Learning ; drug effects ; Cytidine Diphosphate Choline ; pharmacology ; Infarction, Middle Cerebral Artery ; physiopathology ; Male ; Maze Learning ; drug effects ; Nootropic Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spatial Behavior ; drug effects