Effects of shock waves on tenocyte proliferation and extracellular matrix metabolism

The shock wave is an effective noninvasive modality for resolving various tendon pathologies. However, scientific rationale and mechanism of shock wave therapy remains limited. This study aims to investigate the effects of shock waves and their biochemical mechanisms on tenocyte proliferation and collagen synthesis. Tenocytes harvested from Achilles tendons of Sprague-Dawley rats were used in this study. Cell viability was assayed by trypan blue exclusion methods. The colorimetric assay was determined to evaluate the mitochondria activity of the tenocytes after shock wave exposure. Synthesis of collagen, nitric oxide (NO) and transforming growth factor-β1 (TGF-β1) were determined and their gene expression was also studied. The results showed that there was a dose-dependent impairment of cell viability observed in 0.36 mJ/mm² and 0.68 mJ/mm² stimulation. In the proliferation assay, low energy level with low impulses (0.36 mJ/mm² with 50 and 100 impulses) showed positive stimulatory effects, whereas the high energy level with high impulses (0.68 mJ/mm² with 250 and 500 impulses) had significant inhibitory effects. At 0.36 mJ/mm², 100 impulse shock waves treatment, up-regulation of proliferating cell nuclear antigen (PCNA) (at 6 and 24 h) and collagen type I, collagen type III and TGF-β1 gene expression (at 24 h) were observed; these were followed by the increases in NO production (at 24 h), TGF-β1 release (at 48 and 96 h) and collagen synthesis (at the 7th day). This study revealed that shock waves can stimulate tenocyte proliferation and collagen synthesis. The associated tenocyte proliferation is mediated by early up-regulation of PCNA and TGF-β1 gene expression, endogenous NO release and synthesis and TGF-β1 protein and then collagen synthesis. (E-mail: jssun@ym.edu.tw)     

Nicotine dependence subtypes: association with smoking history, diagnostic criteria and psychiatric disorders in 5440 regular smokers from the Vietnam Era Twin Registry

Studies suggest empirically derived subtypes of nicotine dependence exist in young adult populations with short smoking careers. It is not known if classes of dependence exist in middle aged smokers with longer smoking careers and whether these classes reflect quantitative or qualitative differences. It is not known if psychiatric disorders are associated with classes of nicotine dependence. Nicotine dependence symptoms were obtained from a 1992 administration of the Diagnostic Interview Schedule. Latent Class Analyses (LCA) was computed using data from 5440 members of the Vietnam Era Twin Registry. LCA was used to derive significantly different classes of nicotine dependence, which were assessed for their association with smoking history, nicotine dependence, and other psychiatric disorders. The LCA model which best fit the data was a 4 class solution characterized by severity. Age onset of regular smoking decreased with more severe classes. Cigarette consumption, failed cessation and psychiatric disorders were associated with more severe classes. Empirically derived subtypes of nicotine dependence are mostly characterized by increasing severity. Suggestions for refinement of nicotine dependence diagnostic criteria are discussed.     

Sex differences in language dysfunction in schizophrenia

OBJECTIVE: Normal sex differences in language functions are disrupted in schizophrenia. However, identification of specific language components most vulnerable in schizophrenia and how they may differ by sex remain unexamined. The current study investigated this issue in the domains of phonology, semantics, and grammar, which have been closely linked with neuroanatomic regions for which sex differences have been identified. METHOD: Thirty-one outpatients with DSM-III-R schizophrenia and 27 healthy subjects comparable within sex on age, handedness, parental socioeconomic status, and ethnicity were systematically ascertained from a Boston catchment area. The subjects were administered an extensive language battery in the context of a comprehensive neuropsychological battery that included measures of phonology, semantics, and grammar. RESULTS: Male patients performed significantly worse than their healthy counterparts on all three domains, with phonology least affected. In contrast, language function was relatively preserved in the female patients, compared to their healthy counterparts, with phonology most affected. Across domains, the effect sizes in comparisons of male patients and healthy male subjects had a twofold difference, whereas the difference in effect sizes in comparisons of female patients and healthy female subjects was less in all areas. CONCLUSIONS: Findings were consistent with prior evidence of overall language dysfunction in schizophrenia and may have implications for understanding sex differences in neuroanatomic abnormalities in regions associated with phonological processing.     

IQ decline in cross-sectional studies of schizophrenia: methodology and interpretation

Some researchers have compared neuropsychological performance in schizophrenia groups with and without presumed IQ decline. Inherent in this approach is an assumption that group differences are due to different IQ trajectories (stable vs. declining), but neuropsychological differences could be a function of current IQ regardless of the presence or absence of previous IQ decline. We examined this issue in 93 normal controls and in 80 patients classified as having preserved (27.5%), deteriorated (50%), or compromised (22.5%) intellect based on IQ and reading recognition-IQ difference scores. We also examined group differences in verbal and performance IQ. Deteriorated patients had the largest verbal performance-IQ differences. They were more neuropsychologically impaired than the preserved group (average effect size=0.43), but deteriorated patients also had significantly lower current IQs. When subgroups of preserved and deteriorated patients with equivalent current IQs were compared, neuropsychological differences were essentially eliminated (average effect size=0.10); however, both groups were significantly more impaired than controls with similar IQs. Neuropsychological impairment, even in patients with apparently preserved IQ, is consistent with a prefrontal-dysexecutive syndrome. Overall, these results strongly suggest that differences in current neuropsychological function in schizophrenia are attributable primarily to current IQ instead of to IQ trajectory over time.     

A haplotype analysis of CYP2E1 polymorphisms in relation to alcoholic phenotypes in Mexican Americans

Background: Studies regarding the association between the 4 polymorphisms of CYP2E1 (CYP2E1*1D, *5B, *6, and *1B) and alcoholism are inconsistent and inconclusive. The purpose of the present study was to clarify previously discordant studies by haplotype analysis in the Mexican American population. Methods: The 4 polymorphisms of CYP2E1 were studied in 334 alcoholics and 365 controls. Genotype, allele, and haplotype frequency comparisons between alcoholics and controls were assessed. Patterns of linkage disequilibrium (LD) at CYP2E1 were determined. Reconstructed haplotypes were tested for associations with clinical phenotypes (age onset of drinking, Maxdrinks, and smoking status). Results: No significant associations between the 4 polymorphisms of CYP2E1 and alcoholism were revealed by single allele tests. High LD was found between the CYP2E1 c2 and C alleles in Mexican Americans. Eleven haplotypes were present in the 699 participants. The 6 main haplotypes with frequencies higher than 1% made up 97% of the total halpotypes. The frequency of subjects carrying H6 (1C‐c2‐C‐A2) was significantly higher in alcoholics than in controls (p = 0.0001). In contrast, the frequencies of H7 (1C‐c2‐C‐A1) and H10 (1C‐c2‐D‐A1) were significantly lower in alcoholics than in controls (p = 0.0072 for H7 and p = 0.0407 for H10). The frequency of H6 was significantly higher in alcoholics who had late onset of drinking than in nonalcoholic controls. Furthermore, the frequencies of H6 haplotype were also consistently higher in groups who had high number of maximum drinks (9 to 32 drinks) than in controls. When smokers are excluded, the frequencies of H6, H7, and H9 (1C‐c2‐D‐A2) showed statistically significant differences between alcoholics and controls (p < 0.05). Moreover, the association between H6 and alcoholism become more robust when smokers are excluded. Furthermore, the frequency of H1 (1C‐c1‐D‐A2) in alcoholic‐smokers was much higher than in alcoholic‐nonsmokers (p = 0.0028). In contrast, alcoholic‐smokers carried less H2 (1C‐c1‐D‐A1) in comparison with alcoholic‐nonsmokers (p = 0.0417). The H3 (1D‐c2‐C‐A2) frequency in alcoholic‐smokers was much lower than in alcoholic‐nonsmokers (p = 0.0042) and control‐smokers (p = 0.0363). Conclusions: Our data demonstrate that carrying haplotype H6 might enhance susceptibility to developing alcoholism, but possessing the H7 or H10 haplotype appears to decrease this susceptibility. The H6, H7, and H9 haplotypes may play certain roles in different clinical phenotypes in Mexican American alcoholics. In addition, our data suggest that the H1, H2, and H3 haplotypes are associated with alcohol drinking and smoking. These results support that haplotype analysis is much more informative than single allele analysis. Our findings clearly indicate the importance of H6 haplotype in alcohol drinking in Mexican Americans.     

More evidence supports the association of PPP3CC with schizophrenia

Calcineurin is a calcium/calmodulin-dependent protein phosphatase composed of two subunits, a regulatory subunit of calcineurin B (CNB) and a catalytic subunit of calcineurin A (CNA). PPP3CC is the gamma isoform of CNA located at the chromosome 8p21.3 region. To evaluate the association between PPP3CC and schizophrenia in the Taiwanese population, 10 single nucleotide polymorphism (SNP) markers across the gene were genotyped by the method of MALDI-TOF in 218 schizophrenia families with at least two affected siblings. One SNP (rs2272080) located around the exon 1 untranslated region was nominally associated with schizophrenia (P=0.024) and significantly associated with the expression of PPP3CC in lymphoblast cell line; the TT and TG genotype had significantly higher relative expression levels than the GG genotype (P=0.0012 and 0.015, respectively). In further endophenotype stratification, the single locus of rs2272080 and the haplotypes of both two-SNP haplotype (rs7833266-rs2272080) and seven-SNP haplotype (rs2461491-rs2469758-rs2461489-rs2469770-rs2449340-rs1482337-rs2252471) showed significant associations with the subgroup of schizophrenia with deficits of the sustained attention as tested by the continuous performance test (CPT, P<0.05) and the executive functioning as tested by the Wisconsin Card Sorting Test (WCST, P<0.05). The results suggest that PPP3CC gene may be a true susceptibility gene for schizophrenia.     

Neuroanatomic substrates of sex differences in language dysfunction in schizophrenia: a pilot study

OBJECTIVE: This pilot study investigated whether our previous findings of disrupted normal sexual brain dimorphisms in language-associated regions in schizophrenia were linked with our previously reported sex differences in language dysfunction in schizophrenia. METHOD: Nineteen adults with schizophrenia and 15 normal comparisons were tested on phonology, semantics and grammar and underwent structural MRI. RESULTS: Among males, left hippocampal and left planum temporale (PT) abnormalities were associated with phonological, semantic and grammar deficits, accounting for 17-52% and 27-33%, respectively, of variance in diagnostic group differences. Anterior cingulate gyrus was significantly associated with semantics. Among females, right Heschl's Gyrus (HG) and left PT were significantly associated with phonology, right HG with semantics and grammar and right hippocampus with semantics. CONCLUSIONS: These preliminary findings suggest disrupted sexual brain dimorphisms in schizophrenia are associated with sex-specific language deficits, and left hippocampal abnormalities, in particular, contribute to language dysfunction among men. Abnormalities in right cortical temporal regions showed stronger associations with language dysfunction among females.