Intravitreal conbercept for branch retinal vein occlusion induced macular edema: one initial injection versus three monthly injections.

BACKGROUND: To compare the efficacy of one initial intravitreal injection of conbercept (IVC) versus three monthly IVCs in patients with macular edema (ME) after branch retinal vein occlusion (BRVO). Both options were followed by a pro re nata (PRN) retreatment regimen. METHODS: This study retrospectively investigated and followed 60 patients with acute ME secondary to BRVO for over a year. 30 subjects received one initial injection (1 + PRN group); while, 30 received three monthly injections (3 + PRN group). The functional and anatomic outcomes were assessed during each follow-up. RESULTS: The general characteristics of the 60 subjects were as follows: mean [SD] age, 57.43 [13.06] years; 33 [55%] female; 36 [60%] non-ischemic form. Both groups showed a stable gain in visual acuity (VA) with similar logMAR (mean ± SD) (1 + PRN group 0.308 ± 0.399, 3 + PRN group 0.34 ± 0.352) during the first 12 months. Additionally, both groups exhibited a significant reduction in central foveal thickness (CFT) with no statistically significant difference between them (1 + PRN group 222.1 µm ± 197.1 µm, 3 + PRN group 228.4 µm ± 200.2 µm). Both treatment groups had similar improvements in logMAR and anatomic outcomes over time. The stratified analysis showed that patients with the non-ischemic form and those with the ischemic form had similar improvements in VA (0.346 ± 0.366 VS 0.29 ± 0.39, P = 0.575) during the 12 months follow-ups. The number of injections was lower in the 1 + PRN group (4.0 ± 1.6) than in the 3 + PRN group (4.7 ± 1.3) (P = 0.068). No adverse effects or unexpected safety issues were reported in either group. CONCLUSIONS: Conbercept yielded significant improvements in VA and CFT among patients with BRVO induced ME, independent of their retinal ischemia status. The results showed that the 3 + PRN regimen do not lead to better functional outcomes or lower treatment needs in clinical practice as compared to the 1 + PRN regimen.

Architecture of the drug-drug interaction network.

PURPOSE: Drug interaction information has been extensively compiled into large databases. The objective of the present study was to provide a systematic overview of the available drug interaction information, using a network approach. METHODS: The drug-drug interaction information was retrieved from a comprehensive source reference that documents primary drug interaction information over an extended period of time. With careful examination of the information, we identified three continuously growing databases that consisted of 351, 636 and 966 drugs and 742, 1858 and 3351 pairs of interaction, respectively. We then constructed three drug-drug interaction networks in which the interacting drugs were treated as nodes and were connected with links that represent interactions. For each network, we determined the number of interactions that each drug in that network has, and prepared histograms to show the frequency distribution. RESULTS: The frequency distribution or the probability that a given drug has k interactions, P(k), followed a power-law distribution, where the power law exponent was close to -1·5 and was independent of the network size. The results suggested that while the majority of the drugs in the network had few interactions (small k), highly interacting drugs (large k) were rare but contributed most of the network interactions. CONCLUSIONS: The present study demonstrated that drug interaction information can be viewed and analysed as a connecting, growing network. As with many real-world networks, the drug interaction network was scale free, indicating that drug interaction information has been dominated by a relatively small number of highly interacting drugs.

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics.

Noradrenaline and adrenaline are neurotransmitters of the sympathetic nervous system that interact with various adrenergic receptor (ADR) subtypes, and this regulates the basal metabolic rate, thermogenesis and efficiency of energy utilization. We examined a possible role of the gene coding for ADRA1A receptor in weight gain in schizophrenia subjects exposed to antipsychotics. A total of 401 schizophrenia in-patients treated with antipsychotics for >2 years were recruited and a final 394 DNA samples were genotyped. Their body mass indexes (BMIs) were recorded for 12 months and parameterized to be correlated in regression. Among the 58 single-nucleotide polymorphisms (SNPs) genotyped, 44 valid SNPs, which had minor allele frequency > or =0.03, were analyzed in statistics. Linear regression model with age, gender, diabetes, use of typical antipsychotics and use of atypical antipsychotics as covariates, with or without gender interaction, showed evidence of associations between the ADRA1A gene and BMI. Most of the SNPs associated with BMI are located in the promoter and intron regions, and being female appeared to enhance the gene effect. Our study suggests that the ADRA1A gene is involved in weight gain among schizophrenia patients treated with antipsychotics. Further molecular dissection of the ADRA1A gene warrants better understanding on weight gain mechanisms in schizophrenia.

Effects of inulin on performance, egg quality, gut microflora and serum and yolk cholesterol in laying hens.

1. The present study was conducted to investigate the effects of inulin on laying hens. A total of 360 Brown Nick laying hens were divided randomly into 6 groups of 60 with 6 replicates of 10 hens and fed on diets containing 0 (control), 0·1, 0·5, 1·0, 1·5 or 2·0% inulin during the 4-week trial. 2. Dietary supplementation of inulin reduced cholesterol concentration (mg/g yolk) and content (mg/egg) in eggs. Cholesterol content in eggs decreased linearly with increasing levels of dietary inulin level. 3. Supplementation of inulin in diets decreased coliform bacteria counts and pH in the caecum. The lowest coliform bacteria counts (6·30 ± 0·03 log10 cfu/g) and pH (6·47 ± 0·01) were obtained in the 2·0% inulin group, the two indices decreasing by 21·6% and 3·0% respectively, compared with the control group. Coliform bacteria count and pH were changed linearly in accordance with increasing levels of dietary inulin level. Caecal Bifidobacteria counts were increased in the 2·0%-inulin group. 4. Inulin supplementation of layer diets did not appear to have any adverse effects on laying rate, egg weight, feed intake, feed conversion efficiency, cracked-egg rate, eggshell thickness or Haugh unit compared with the control laying hens. 5. Therefore, dietary supplementation with inulin may lead to the development of low-cholesterol chicken eggs as demanded by health-conscious consumers.

Performance of a neuro-fuzzy model in predicting weight changes of chronic schizophrenic patients exposed to antipsychotics.

Artificial intelligence has become a possible solution to resolve the problem of loss of information when complexity of a disease increases. Obesity phenotypes are observable clinical features of drug-naive schizophrenic patients. In addition, atypical antipsychotic medications may cause these unwanted effects. Here we examined the performance of neuro-fuzzy modeling (NFM) in predicting weight changes in chronic schizophrenic patients exposed to antipsychotics. Two hundred and twenty inpatients meeting DSMIV diagnosis of schizophrenia, treated with antipsychotics, either typical or atypical, for more than 2 years, were recruited. All subjects were assessed in the same study period between mid-November 2003 and mid-April 2004. The baseline and first visit's physical data including weight, height and circumference were used in this study. Clinical information (Clinical Global Impression and Life Style Survey) and genotype data of five single nucleotide polymorphisms were also included as predictors. The subjects were randomly assigned into the first group (105 subjects) and second group (115 subjects), and NFM was performed by using the FuzzyTECH 5.54 software package, with a network-type structure constructed in the rule block. A complete learned model trained from merged data of the first and second groups demonstrates that, at a prediction error of 5, 93% subjects with weight gain were identified. Our study suggests that NFM is a feasible prediction tool for obesity in schizophrenic patients exposed to antipsychotics, with further improvements required.

A case of Huntington’s disease presenting with psychotic symptoms and rapid cognitive decline in the early stage

No disponible

Determination of galactose in human blood by high-performance liquid chromatography: comparison with an enzymatic method and application to the pharmacokinetic study of galactose in patients with liver dysfunction.

Galactose, the C-4 epimer of glucose, is an agent of choice for the quantitation of liver function. A simple, precise, and accurate high-performance liquid chromatographic (HPLC) assay with refractive index detection was developed for the determination of galactose in human whole blood. The method consists of organic solvent-heavy metal deproteinization procedures and reversed-phase chromatography on a cation-exchange column in the calcium form. Calibration graphs were linear over the concentration range 100-2500 microgram/mL, with correlation coefficients > 0.999. The within-day coefficient of variation (CV) ranged from 2.08 to 8.94%, and the between-day CV ranged from 1.61 to 10.9%. The limit of quantitation was 100 micrograms/mL in whole blood. However, the limit of detection was 75 micrograms/mL based on a signal-to-noise ratio of > or = 3. Eight structurally related sugars and polyols were investigated to check for potential interferences using the analytical condition of the assay. The possible metabolites of galactose present in the body were also checked to determine the specificity of this assay. The proposed HPLC assay was compared with an enzymatic assay and an excellent correlation was observed (HPLC = 1.0299Enz. - 12.907, r = 0.952, p < 0.001). This HPLC method has been successfully applied to the pharmacokinetic study of galactose in six patients with liver dysfunction. Following the intravenous administration of a dose of 0.5 g/kg body weight, galactose pharmacokinetics followed a nonlinear two-compartment model with Michaelis-Menten elimination from the central compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of guaiphenesin in anti-tussive pharmaceutical preparations containing dextromethorphan by first- and second-derivative ultraviolet spectrophotometry.

Rapid, simple and direct assay procedures based on selective first (D1)- and second (D2)-derivative spectrophotometry, using a zero-crossing technique of measurement at 279.2 and 280.0 nm, respectively, have been developed for the specific determination of guaiphenesin in the presence of dextromethorphan, drugs with closely overlapping absorption spectra, in synthetic admixtures and in pharmaceutical dosage forms (tablets and syrups). The methods do not require extraction with organic solvents and are easier to perform than their conventional counterparts. Calibration graphs were linear (r = 0.99999 for D1 and 0.99969 for D2, respectively). Good selectivity, accuracy and precision were found. However, the performance of the analysis of guaiphenesin by the second-derivative mode deteriorated when the ratio of dextromethorphan to guaiphenesin was greater than one. Thus, the first-derivative spectrophotometry is the method of choice for the assay of tablets and syrups containing the two drugs.

Allometric scaling of xenobiotic clearance: uncertainty versus universality.

Statistical analysis and Monte Carlo simulation were used to characterize uncertainty in the allometric exponent (b) of xenobiotic clearance (CL). CL values for 115 xenobiotics were from published studies in which at least 3 species were used for the purpose of interspecies comparison of pharmacokinetics. The b value for each xenobiotic was calculated along with its confidence interval (CI). For 24 xenobiotics (21%), there was no correlation between log CL and log body weight. For the other 91 cases, the mean +/- standard deviation of the b values was 0.74 +/- 0.16; range: 0.29 to 1.2. Most (81%) of these individual b values did not differ from either 0.67 or 0.75 at P = 0.05. When CL values for the subset of 91 substances were normalized to a common body weight coefficient (a), the b value for the 460 adjusted CL values was 0.74; the 99% CI was 0.71 to 0.76, which excluded 0.67. Monte Carlo simulation indicated that the wide range of observed b values could have resulted from random variability in CL values determined in a limited number of species, even though the underlying b value was 0.75. From the normalized CL values, four xenobiotic subgroups were examined: those that were (i) protein, and those that were (ii) eliminated mainly by renal excretion, (iii) by metabolism, or (iv) by renal excretion and metabolism combined. All subgroups except (ii) showed a b value not different from 0.75. The b value for the renal excretion subgroup (21 xenobiotics, 105 CL values) was 0.65, which differed from 0.75 but not from 0.67.

Severity of psychosis syndrome and change of metabolic abnormality in chronic schizophrenia patients: severe negative syndrome may be related to a distinct lipid pathophysiology.

BACKGROUND: Metabolic abnormality is common among schizophrenia patients. Some metabolic traits were found associated with subgroups of schizophrenia patients. OBJECTIVES: We examined a possible relationship between metabolic abnormality and psychosis profile in schizophrenia patients. METHOD: Three hundred and seventy-two chronic schizophrenia patients treated with antipsychotics for more than 2 years were assessed with the Positive and Negative Syndrome Scale. A set of metabolic traits was measured at scheduled checkpoints between October 2004 and September 2006. RESULTS: Multiple regressions adjusted for sex showed negative correlations between body mass index (BMI) and total score and all subscales; triglycerides (TG) was negatively correlated with total score and negative syndrome, while HDLC was positively correlated with negative syndrome. When sex interaction was concerned, total score was negatively correlated with BMI but not with others; negative syndrome was negatively correlated with BMI and positively with HDLC. No metabolic traits were correlated with positive syndrome or general psychopathology. CONCLUSIONS: Loss of body weight is a serious health problem in schizophrenia patients with severe psychosis syndrome, especially the negative syndrome. Schizophrenia patients with severe negative syndrome may have a distinct lipid pathophysiology in comparison with those who were less severe in the domain.

A comparative efficacy and safety study of long-acting risperidone injection and risperidone oral tablets among hospitalized patients: 12-week randomized, single-blind study.

OBJECTIVE: The superiority of risperidone long-acting injection (RLAI) over oral typical and atypical antipsychotics demonstrated in previous studies may be related to the improved drug compliance. The aim of the 12-week randomized, single-blind study was to test whether the superiority of RLAI remained among hospitalized patients that drug compliance could be optimally controlled. METHODS: Fifty hospitalized stable schizophrenic patients, who had maintained on oral risperidone for more than 3 months, were randomized to the RLAI and oral risperidone group. Finally 49 patients (98 %) completed the study, and no dose change of oral risperidone, or RLAI was noted among all patients. RESULTS: The RLAI group showed significantly increased positive score of Positive and Negative Syndrome Scale (PANSS) than the risperidone group (0.72 +/- 3.52 vs. -1.24 +/- 3.81, p = 0.022), but without significance difference for the PANSS total, negative and general psychopathology scores. The RLAI group also showed a significantly improved Udvalg for Kliniske Undersogelser (UKU) Scale (p = 0.037), social life domains of Short-Form Health Survey (SF-36) (p = 0.011), and reduced prolactin level (p = 0.001). CONCLUSION: The results indicated that with optimal controlling of drug compliance among hospitalized patients, RLAI showed no benefit of efficacy over oral risperidone, but with advantages of improved side-effect profiles, social life ratings, and reduced prolactin levels.

The effect of aging on the pharmacokinetics of nalbuphine in rabbits.

For the purpose of selecting an animal model for the study of the aging effect on the pharmacokinetics of nalbuphine, the pharmacokinetic properties in young and in aged rabbits were reported. Thirty-one healthy New Zealand white rabbits ranging in ages (mean) from three months to 43 months (six three months old, group I; nine eight months old, group II; nine 18 months old, group III; and seven 43 months old, group IV) were included in the study. After intravenous bolus injection of nalbuphine (10 mg kg-1) to each rabbit, plasma samples were collected and analysed for nalbuphine by a high-performance liquid chromatography method. The plasma concentration-time data regarding nalbuphine were successfully fitted to a linear two-compartment open model. The elimination half-life of nalbuphine in rabbits increased significantly with age. Consequently, clearance decreased significantly with age. The parameter AUCO-affinity, which is derived from dose/clearance, increased significantly with age. The effect of aging on the pharmacokinetics of nalbuphine in rabbits is quite similar to that in humans. From the present study, it is concluded that rabbits may be suitable for the study of aging effects on the pharmacokinetics of nalbuphine.

Novel single-point plasma or saliva dextromethorphan method for determining CYP2D6 activity.

O-Demethylation of dextromethorphan co-segregates with 4-hydroxylation of debrisoquin and is used for CYP2D6 phenotyping. In most previous studies, 8-h urinary samples were collected for determining the dextromethorphan metabolic ratio (dextromethorphan/dextrorphan molar ratio). In addition, a salivary sampling at 3 h had been suggested for the phenotyping. To evaluate the repeatability and validity of previously reported and other potential phenotyping methods, we determined the metabolic ratios from urine samples (for various intervals), or from plasma or saliva (at varying time points) after repetitive single doses of immediate-release or repetitive multiple doses of controlled-release dextromethorphan preparations. For the single-dose study, each of 12 subjects received 15 mg of immediate-release dextromethorphan in period I and period II, respectively, with a 1-week washout period. For the multiple-dose study, each of 16 subjects received 60 mg controlled-release dextromethorphan twice daily for 5 days in period I and period II, respectively, with a 2-week washout period. Dextromethorphan and dextrorphan were assayed by high-performance liquid chromatography. In the single-dose study, most metabolic ratios revealed good repeatabilities for the two periods (paired t test). The metabolic ratio from urine collected for 4 h, 6 h, 8 h or 12 h from plasma at any time between 1 h and 5 h or at 8 h, or from saliva at 2 h or 6 h, could reflect that from 0- to 24-h urine or AUCinfinity. In the multiple-dose study, all metabolic ratios revealed good repeatabilities. The plasma metabolic ratio at any time between 0.5 h and 10 h or the saliva metabolic ratio at any time between 3 h and 12 h, but not the urine metabolic ratio from any interval, could predict the metabolic ratio from ACUSStau. The 2 h, 3 h, 4 h or 5 h plasma metabolic ratio and 6 h saliva metabolic ratios after a single dose correlated significantly with their corresponding multiple-dose metabolic ratio (r > 0.8, P < .05). In conclusion, the plasma sample at 2 h, 3 h, 4 h or 5 h or the saliva sample at 6 h in either the single immediate-release (15 mg) or the multiple controlled-release dose (60 mg) procedure could be used for determining the dextromethorphan metabolic ratio.