A novel synthetic method for 3-hydroxyhomoisoflavanone

A novel synthetic method was developed for 3-hydroxyhomoisoflavanone. Treatment of aryllithium14 to aldehyde13 which was obtained from dihydroxylation of10, followed by cycloetherification to give 3-hydroxyhomoisoflavanones.     

A novel bromolactonization reaction using racemic 3-bromo-5-isobutyl-5-methylhydantoin

By using racemic 3-bromo-5-isobutyl-5-methylhydantoin (3a′) in dry N, N-dimethylformanide which is a model reagent for asymmetric bromolactonization, bromolactonization of a series of olefinic acids was carried out to furnish corresponding bromolactones in moderate yields.     

The absolute configuration of ketoprofen

(+)-Ketoprofen was obtained from resolution with (S)(+)-2-amino-1-butanol and its absolute configuration was determined to be (S) by chemical correlation with (S)(+)-ethyl hydratropate using Beckmann rearrangement as a key step.     

Intraoperative facial electromyography and brainstem auditory evoked potential findings in microvascular decompression for hemifacial spasm: correlation with postoperative delayed facial palsy

Background: Delayed facial palsy (DFP) after microvascular decompression (MVD) in patients with hemifacial spasm (HFS) is not uncommon, but the cause remains unknown. Objectives: To assess whether intraoperative electromyography (EMG) and brainstem auditory evoked potential (BAEP) can predict DFP after MVD. Methods: Between September 2009 and February 2011 we examined 86 patients, 9 of whom (10.4%) developed DFP after MVD on the same side. All patients underwent MVD and were followed-up for a median period of 13 months (range 6-22). We retrospectively examined intraoperative facial EMG and BAEP findings using our MVD patients' registry. We excluded secondary HFS and immediate postoperative facial palsy after MVD in this study. We assessed the prevalence and clinical characteristics of DFP and compared EMG and BAEP findings between DFP and non-DFP groups. Results: All patients recovered completely, with a mean time to recovery of 37.8 days (range 22-57). There were no significant differences between DFP and non-DFP patients in terms of the amplitude and latency of intraoperative EMG and BAEP. Conclusion: The usefulness of intraoperative facial EMG and BAEP is limited and cannot predict DFP after MVD for HFS. We speculate that DFP after MVD is not associated with permanent nerve damage according to the EMG findings.     

Fluorescence immunohistochemistry and confocal scanning laser microscopyA protocol for studies of joint innervation

We have developed a reliable technique for labeling and examining neural structures in soft tissues associated with articular joints and have tested it in human wrist joints under various specimen-related conditions. The labeling protocol employs an immunohistochemical process with a panneuronal marker (PGP 9.5) as the primary antibody and Alexa Fluor 488 as the fluorescing secondary antibody. Imaging was done using a confocal laser scanning microscope, which produced exceptionally detailed three-dimensional images of nerve endings and transiting nerve fibers from thick sections of wrist joint ligaments obtained from human cadavers. The protocol provided a practical postmortem window for specimen acquisition and processing without significant apparent worsening of image quality. The images produced are resistant to fading with repeated exposure to a fluorescent light source, which gives many opportunities for observation. Background staining is minimal, producing high contrast labeling of target tissues, which, in turn, enhances image analysis.     

Electromyographic analysis of traditional and nontraditional abdominal exercises: implications for rehabilitation and training

BACKGROUND AND PURPOSE: Performing nontraditional abdominal exercises with devices such as abdominal straps, the Power Wheel, and the Ab Revolutionizer has been suggested as a way to activate abdominal and extraneous (nonabdominal) musculature as effectively as more traditional abdominal exercises, such as the crunch and bent-knee sit-up. The purpose of this study was to test the effectiveness of traditional and nontraditional abdominal exercises in activating abdominal and extraneous musculature. SUBJECTS: Twenty-one men and women who were healthy and between 23 and 43 years of age were recruited for this study. METHODS: Surface electromyography (EMG) was used to assess muscle activity from the upper and lower rectus abdominis, external and internal oblique, rectus femoris, latissimus dorsi, and lumbar paraspinal muscles while each exercise was performed. The EMG data were normalized to maximum voluntary muscle contractions. Differences in muscle activity were assessed by a 1-way, repeated-measures analysis of variance. RESULTS: Upper and lower rectus abdominis, internal oblique, and latissimus dorsi muscle EMG activity were highest for the Power Wheel (pike, knee-up, and roll-out), hanging knee-up with straps, and reverse crunch inclined 30 degrees. External oblique muscle EMG activity was highest for the Power Wheel (pike, knee-up, and roll-out) and hanging knee-up with straps. Rectus femoris muscle EMG activity was highest for the Power Wheel (pike and knee-up), reverse crunch inclined 30 degrees, and bent-knee sit-up. Lumbar paraspinal muscle EMG activity was low and similar among exercises. DISCUSSION AND CONCLUSION: The Power Wheel (pike, knee-up, and roll-out), hanging knee-up with straps, and reverse crunch inclined 30 degrees not only were the most effective exercises in activating abdominal musculature but also were the most effective in activating extraneous musculature. The relatively high rectus femoris muscle activity obtained with the Power Wheel (pike and knee-up), reverse crunch inclined 30 degrees, and bent-knee sit-up may be problematic for some people with low back problems.     

IgA Antibody Response of Swine to Foot-and-Mouth Disease Virus Infection and Vaccination

Foot-and-mouth disease virus (FMDV) continues to be a significant economic problem worldwide. Control of the disease involves the use of killed-virus vaccines, a control measure developed decades ago. After natural infection, the primary site of replication of FMDV is the pharyngeal area, suggesting that a mucosal immune response is the most effective. Humoral immunity to killed-virus vaccination induces antibodies that can prevent the clinical disease but not local infection. Determining whether infection or vaccination stimulates IgA-mediated local immunity depends on the method of analysis. Different assays have been described to analyze the quality of antibody responses of cattle and swine to FMDV, including indirect double-antibody sandwich enzyme-linked immunosorbent assay (IDAS-ELISA) and antibody capture assay-ELISA (ACA-ELISA). We tested these assays on swine and show that vaccinated animals had FMDV-specific IgM and IgG but no IgA in either serum or saliva. After the infection, both assays detected FMDV-specific IgM, IgG, and IgA in serum. Notably, serum IgA was more readily detected using the ACA-ELISA, whereas IgA was not detected in saliva with this assay. FMDV-specific IgA antibodies were detected in saliva samples using the IDAS-ELISA. These data show that parenterally administered, killed-virus vaccine does not induce a mucosal antibody response to FMDV and illuminates limitations and appropriate applications of the two ELISAs used to measure FMDV-specific responses. Further, the presence of the IgA antivirus in serum correlates with the presence of such antibodies in saliva.Foot-and-mouth disease virus (FMDV) continues to be a significant economic problem worldwide. In FMDV-free countries, an outbreak of the virus freezes the export of all animal products, causing significant loss of revenue to the livestock industry. Eradication of the disease from areas of endemicity involves the use of killed-virus vaccines, a control measure developed decades ago. The vaccine offers clinical protection against FMDV, but it does not prevent virus excretion or the establishment of latency after challenge infection (14). Recovery from FMDV and protection from reinfection are associated predominantly with the presence of circulating neutralizing antibody (20, 25, 32).Transmission of FMDV between animals is primarily via oral-pharyngeal exposure from contaminated feed and aerosols emitted from infected animals. This has led to a particular interest in the local, mucosal immune response to FMDV infection in the pharynx since, following exposure, this region is the most common site for primary virus replication (30, 36). Unfortunately, analysis of mucosal immunity has essentially been limited to assessment of immunoglobulin A (IgA) responses to FMDV infection of swine. Alternatively, the virus can gain direct entry into the skin through cuts or abrasions, particularly during infection of swine, as reviewed by Alexandersen and colleagues (2). The latter route of viral entry is more common in swine than in other susceptible species.The role of T cells in stimulating B cell proliferation and subsequent differentiation to high-affinity antibody production in the swine response to FMDV is of particular interest. In the response of other species to different pathogens, it has been clearly demonstrated that both Th1 and Th2 responses contribute to effective immunity and clearance of pathogens (4, 26, 28, 33, 34). Manipulating vaccine formulations to target immune responses will be useful for FMDV prophylactics in swine and cattle, but the present knowledge of immune responses in these species offers little insight into the importance of the Th1/Th2 paradigm in effective antiviral immunity. Thus, extrapolating the Th1/Th2 paradigm of mice to swine is problematic.In mice, the B cell switch from IgM to IgG2b antibody secretion is mediated by Th1 cytokines, specifically, gamma interferon (IFN-γ), whereas Th2 cytokines, including interleuken-4 (IL-4), IL-5, IL-13, and transforming growth factor β (TGF-β), accompany class switch to IgG1, IgG3, IgE, and IgA. However, IgG1 and IgG2b are not homologous immunoglobulins among distantly related mammals since speciation preceded subclass diversification (13, 23).Further complicating our understanding of antibody responses in pigs is the fact that there are six subclasses of porcine IgG, five of which occur in at least two allelic forms (13). IgG1 is transcribed predominately in fetal and adult swine but not in the ileal Peyer''s patches and mesenteric lymph nodes of fetal and neonatal piglets, where IgG3 predominates (11). IgG2 is poorly transcribed in all tissues of fetal and neonatal piglets. IgG3, the primordial porcine IgG, is most 5′ in the CH locus and, based on sequences motifs, is best equipped to activate complement and bind to Fcγ receptors (13, 17a). Currently, only two monoclonal antibodies (MAbs) that are described as specific for IgG1 and IgG2 are available. Based on preliminary results, anti-IgG1 is quite likely IgG1 specific, whereas the anti-IgG2 MAb likely recognizes an infraclass group that includes IgG2, IgG4, and IgG6. Since purified forms of IgG4 and IgG6 are not yet available, this has yet to be tested.There are other factors that complicate understanding antibody responses to viral infection of mucosal surfaces in swine. In their studies on the distribution of antibody-containing cells, Bianchi and colleagues recognized differential reactivities among anti-porcine IgA MAb, which they suggested might reflect different IgA subclasses, as in humans (3). At nearly the same time, the porcine Cα gene was cloned and was shown to occur in two allelic forms, one of which was missing 4 amino acids of the hinge due to a splice accepter site mutation (5, 6). Sera from swine homozygous for IgAa and IgAb were exchanged to show that the MAbs generated by Bianchi and colleagues differentially recognized the two allotypic variants (29). The distribution of the two allotypes appears to be founder and breed associated, with IgAa occurring in the highest frequency (29).The study reported here focuses on the mucosal antibody response of swine and utilizes isotype-specific reagents in two different, sensitive enzyme-linked immunosorbent assays (ELISAs). The comparison of assays for determination of the quality of antibody responses to FMDV addresses the limitations of presently available reagents. We tested for antibody responses in serum and saliva at 7, 14, or 21 days postvaccination (dpv) with a single dose of vaccine and compared the responses to those resulting from direct inoculation of pigs or following contact transmission of infection. FMDV-specific IgA, IgM, and IgG antibodies were readily detected in serum after infection, and IgA was detected in the saliva of the same animals. However, following vaccination, there were IgM and IgG responses in serum but no IgA antibodies in serum or saliva. These results illuminate the need to develop alternative FMDV vaccines designed for more efficient mucosal delivery and the induction of a mucosal IgA response that is predicted to yield better control of FMDV in an outbreak.     

Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia

The posterior cingulate cortex (PCC), a key component of the limbic system, has been implicated in the pathology of schizophrenia because of its sensitivity to NMDA receptor antagonists. Recent studies have shown that the PCC is dysfunctional in schizophrenia, and it is now suspected to be critically involved in the pathogenesis of schizophrenia. Studies also suggest that there are abnormalities in muscarinic and GABAergic neurotransmission in schizophrenia. Therefore, in the present study we used quantitative autoradiography to investigate the binding of [(3)H]pirenzepine, [(3)H]AF-DX 384 and [(3)H]muscimol, which respectively label M1/4 and M2/4 muscarinic and GABA(A) receptors, in the PCC of schizophrenia and control subjects matched for age and post-mortem interval. The present study found that [(3)H]pirenzepine binding was significantly decreased in the superficial (-24%, p=0.002) and deep (-35%, p<0.001) layers of the PCC in the schizophrenia group as compared with the control group. In contrast, a dramatic increase in [(3)H]muscimol binding was observed in the superficial (+112%, p=0.001) and deep layers (+100%, p=0.017) of the PCC in the schizophrenia group. No difference was observed for [(3)H]AF-DX 384 binding between the schizophrenia and control groups. The authors found a significant inverse correlation between [(3)H]pirenzepine binding in the deep cortical layers and [(3)H]muscimol binding in the superficial layers (rho=-0.732, p=0.003). In addition, negative correlations were also found between age and [(3)H]pirenzepine binding in both superficial and deep cortical layers (rho=-0.669 p=0.049 and rho=-0.778, p=0.014), and between age of schizophrenia onset and [(3)H]AF-DX 384 binding (rho=-0.798, p=0.018). These results for the first time demonstrated the status of M1/M4, M2/M4 and GABA(A) receptors in the PCC in schizophrenia. Whilst the exact mechanism causing these alterations is not yet known, a possible increased acetylcholine and down regulated GABA stimulation in the PCC of schizophrenia is suggested.