OBJECTIVETo investigate the dynamic expression of placenta growth factor (PLGF) in the lungs with paraquat (PQ)-induced pulmonary fibrosis.

METHODSForty-two adult healthy female Sprague-Dawley (SD) rats were randomly divided into two groups: the control group and the PQ group. Each group was divided into three subgroups, seven animals each. The rats in PQ group were treated intragastrically (ig) with PQ (40 mg/kg) and the rats in control group were treated with the same volume of saline at the beginning of the experiment. The animals of model and control group were sacrificed and lungs were harvested on the 7(th), 14(th) and 28th days respectively. A semiquantitative assay of histological examination and hydroxyproline in lung tissues were used to determine the severity of alveolitis and fibrosis. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of PLGF.

RESULTSHydroxyproline contents in lung tissue were significantly increased after PQ administration. Inflammatory cell infiltration and fibrotic scores were more prominent in the model group compared to the control group. Further study showed that PLGF mRNA on day 7, 14 and 28 (1.28 +/- 0.29, 0.80 +/- 0.07, 0.65 +/- 0.13) and positive index of protein expression (2.27 +/- 0.34, 1.78 +/- 0.41, 1.25 +/- 0.69) in the PQ group were all upregulated as compared with those of the control group.

CONCLUSIONThe PLGF expression in the lung tissue in rats with paraquat-induced pulmonary fibrosis is upregulated.

Animals ; Disease Models, Animal ; Female ; Hydroxyproline ; metabolism ; Lung ; metabolism ; pathology ; Paraquat ; poisoning ; Placenta Growth Factor ; Pregnancy Proteins ; genetics ; metabolism ; Pulmonary Fibrosis ; chemically induced ; metabolism ; pathology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Calcium calmodulin-dependent kinase Ⅱ (CaMKⅡ) can be more active in patients with left ventricular hypertrophy (LVH), which in turn causes phosphorylation of ryanodine receptors, resulting in inactivation and the instability of intracellular calcium homeostasis. The present study aimed to determine the effect of CaMKⅡ–ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia. METHODS: Forty New Zealand rabbits were randomized into four groups (10 per group): sham group, LVH group, KN-93 group (LVH+KN-93), and ryanodine group (LVH+ryanodine). Rabbits in the LVH, KN-93, and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta, while those in the sham group did not undergo the coarctation. After eight weeks, action potentials (APs) were recorded simultaneously in the endocardium and epicardium, and a transmural electrocardiogram (ECG) was also recorded in the rabbit left ventricular wedge model. Drugs were administered to the animals in the KN-93 and ryanodine groups, and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline (1 mol/L) and high-frequency stimulation. RESULTS: The frequency (animals/group) of triggered APs was 0/10 in the sham group, 10/10 in the LVH group, 4/10 in the KN-93 group, and 1/10 in the ryanodine group. The frequencies of ventricular tachycardia were 0/10, 9/10, 3/10, and 1/10, respectively. The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10, 7/10, 2/10, and 1/10, respectively. The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group (P<0.05). CONCLUSIONS: KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH. The CaMKⅡ–ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.

OBJECTIVETo investigate the relationship of susceptibility loci in chromosomes 1q21-25 and 6p21-25 and schizophrenia subtypes in Chinese population.

METHODSA genomic scan and parametric and non-parametric analyses were performed on 242 individuals from 36 schizophrenia pedigrees, including 19 paranoid schizophrenia and 17 undifferentiated schizophrenia pedigrees, from Henan province of China using 5 microsatellite markers in the chromosome region 1q21-25 and 8 microsatellite markers in the chromosome region 6p21-25, which were the candidates of previous studies. All affected subjects were diagnosed and typed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised (DSM-IV-TR; American Psychiatric Association, 2000). All subjects signed informed consent.

RESULTSIn chromosome 1, parametric analysis under the dominant inheritance mode of all 36 pedigrees showed that the maximum multi-point heterogeneity Log of odds score method (HLOD) score was 1.33 (α = 0.38). The non-parametric analysis and the single point and multi-point nonparametric linkage (NPL) scores suggested linkage at D1S484, D1S2878, and D1S196. In the 19 paranoid schizophrenias pedigrees, linkage was not observed for any of the 5 markers. In the 17 undifferentiated schizophrenia pedigrees, the multi-point NPL score was 1.60 (P= 0.0367) at D1S484. The single point NPL score was 1.95(P= 0.0145) and the multi-point NPL score was 2.39 (P= 0.0041) at D1S2878. Additionally, the multi-point NPL score was 1.74 (P= 0.0255) at D1S196. These same three loci showed suggestive linkage during the integrative analysis of all 36 pedigrees. In chromosome 6, parametric linkage analysis under the dominant and recessive inheritance and the non-parametric linkage analysis of all 36 pedigrees and the 17 undifferentiated schizophrenia pedigrees, linkage was not observed for any of the 8 markers. In the 19 paranoid schizophrenias pedigrees, parametric analysis showed that under recessive inheritance mode the maximum single-point HLOD score was 1.26 (α = 0.40) and the multi-point HLOD was 1.12 (α = 0.38) at D6S289 in the chromosome 6p23. In nonparametric analysis, the single-point NPL score was 1.52 (P= 0.0402) and the multi-point NPL score was 1.92 (P= 0.0206) at D6S289.

CONCLUSIONSusceptibility genes correlated with undifferentiated schizophrenia pedigrees from D1S484, D1S2878, D1S196 loci, and those correlated with paranoid schizophrenia pedigrees from D6S289 locus are likely present in chromosome regions 1q23.3 and 1q24.2, and chromosome region 6p23, respectively.

Adult ; Chromosomes, Human ; Genetic Linkage ; Genetic Loci ; Genetic Predisposition to Disease ; Humans ; Microsatellite Repeats ; genetics ; Middle Aged ; Schizophrenia ; genetics ; Young Adult