Unusual ent-Labdane Diterpenoid Dimers and their Selective Activation of TRPV Channels.

Five unusual dimers of ent-labdane diterpenoids (1-5) were isolated and identified from Andrographis paniculata, a famous medicinal plant. Bisandrographolide E (1) represents the first example of a labdane dimer possessing an unprecedent tricyclic system that comprised a spiroketal moiety fused with a ketal-γ-lactone unit in its skeleton. Its biosynthetically related intermediates, all four stereoisomers at C-12 and C-15', bisandrographolides F (2, a new compound) and A-C (3-5), were obtained at the same time. The steric configurations of the newly formed asymmetric carbons in 1-5 were first solved by single-crystal X-ray diffraction of the diacetone derivatives of 2-4 and ECD and NMR calculations of 1. More importantly, bisandrographolides 1-5, with different chemical structures or absolute configurations at C-12 and C-15', selectively activated different TRPV1-4 channels and protected cardiomyocytes from hypoxia-reoxygenation injury. Among them, 5 with 12R/15'S configuration activated TRPV1 most effectively and displayed the best cardiomyocyte protection.

Intensity Dependence of Auditory Evoked Potentials in Primary Dysmenorrhea.

Some studies suggest that women with primary dysmenorrhea have distinct emotional or personality features. For example, they might exaggerate their responses to external stimuli, such as to intensity-increasing auditory stimuli. Fifteen women with primary dysmenorrhea and 15 healthy women were invited to undergo tests of the intensity dependence of auditory evoked potentials (IDAEP), the Functional and Emotional Measure of Dysmenorrhea, and the Plutchik-van Praag Depression Inventory. Study participants with dysmenorrhea showed higher Functional and Emotional scale scores and stronger IDAEP. Regarding the IDAEP generation, the source inversion of N1 and P2 disclosed the activated bilateral superior temporal gyri, medial and superior prefrontal gyri in all participants, and additionally, the middle frontal gyri in dysmenorrhea patients. We report a pronounced IDAEP in primary dysmenorrhea, which indicates the decreased cerebral serotonergic innervations and points to increased activations in the prefrontal and frontal areas in the disorder. PERSPECTIVE: Using an IDAEP technique, the authors found decreased serotonergic innervation and altered cerebral activation in women with primary dysmenorrhea, which might offer some pharmacotherapeutic clues for the disorder.

Sitagliptin attenuated brain damage and cognitive impairment in mice with chronic cerebral hypo-perfusion through suppressing oxidative stress and inflammatory reaction.

BACKGROUND: Sitagliptin, a new antidiabetic drug that inhibits dipeptidyl peptidase (DPP)-4 enzyme activity, has been reported to possess neuroprotective property. We tested the protective effects of sitagliptin against chronic cerebral hypoperfusion (CHP) in mice after bilateral carotid artery stenosis (BCAS). METHOD: Thirty C57BL/6 mice were divided into three groups: sham control (n = 10), CHP (n = 10) and CHP-sitagliptin (orally 600 mg/kg/day) (n = 10). Working memory was assessed with novel-object recognition test. MRI was performed at day 0 and day 90 after BCAS procedure prior to sacrifice. RESULTS: Immunohistochemical (IHC) staining showed significantly enhanced white matter lesions, microglia activation and astrocytosis of white matter in CHP group than in sham control, but the changes were significantly suppressed after sitagliptin treatment (all P < 0.01). The mRNA expressions of inflammatory [tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein (MCP-1) and matrix metalloproteinase (MMP)-2] and apoptotic (Bax) biomarkers showed an identical pattern, whereas the anti-inflammatory (interleukin, IL-10) and antiapoptotic (Bcl-2) biomarkers showed an opposite pattern compared with that of IHC among all groups (all P < 0.01). The protein expressions of oxidative stress (NOX-I, NOX-II, nitrotyrosin, oxidized protein), inflammatory [nuclear factor-kappa B (NF-κB), TNF-α and MMP-2], apoptotic [mitochondrial Bax, cleaved poly(ADP-ribose) polymerase (PARP)] and DNA-damage (γ-H2AX) markers showed an identical pattern, while expression pattern of antiapoptotic marker (Bcl-2) was opposite to that of IHC (all P < 0.01). Glycogen-like peptide-1 receptor protein expression progressively increased from sham control to CHP-sitagliptin (P < 0.01). The short-term working-memory loss and MRI/diffusion tensor imaging (DTI) showed a pattern identical to that of IHC in all groups (all P < 0.01). CONCLUSION: Sitagliptin protected against cognitive impairment and brain damage in a murine CHP model.

EEG theta power and coherence to octave illusion in first-episode paranoid schizophrenia with auditory hallucinations.

BACKGROUND: The exact mechanism behind auditory hallucinations in schizophrenia remains unknown. A corollary discharge dysfunction hypothesis has been put forward, but it requires further confirmation. Electroencephalography (EEG) of the Deutsch octave illusion might offer more insight, by demonstrating an abnormal cerebral activation similar to that under auditory hallucinations in schizophrenic patients. METHODS: We invited 23 first-episode schizophrenic patients with auditory hallucinations and 23 healthy participants to listen to silence and two sound sequences, which consisted of alternating 400- and 800-Hz tones. EEG spectral power and coherence values of different frequency bands, including theta rhythm (3.5-7.5 Hz), were computed using 32 scalp electrodes. Task-related spectral power changes and task-related coherence differences were also calculated. Clinical characteristics of patients were rated using the Positive and Negative Syndrome Scale. RESULTS: After both sequences of octave illusion, the task-related theta power change values of frontal and temporal areas were significantly lower, and the task-related theta coherence difference values of intrahemispheric frontal-temporal areas were significantly higher in schizophrenic patients than in healthy participants. Moreover, the task-related power change values in both hemispheres were negatively correlated and the task-related coherence difference values in the right hemisphere were positively correlated with the hallucination score in schizophrenic patients. LIMITATIONS: We only tested the Deutsch octave illusion in primary schizophrenic patients with acute first episode. Further studies might adopt other illusions or employ other forms of schizophrenia. CONCLUSION: Our results showed a lower activation but higher connection within frontal and temporal areas in schizophrenic patients under octave illusion. This suggests an oversynchronized but weak frontal area to exert an action to the ipsilateral temporal area, which supports the corollary discharge dysfunction hypothesis.

Passive event-related potentials to a single tone in treatment-resistant depression, generalized anxiety disorder, and borderline personality disorder patients.

PURPOSE: Treatment-resistant depression is comorbid with personality or anxiety disorder; how passive attention functions in these disorders remains unknown. A single tone-elicited event-related potential P3 component (passive P3) might help to characterize the passive attention in these disorders. METHODS: The passive P3 test was applied to 32 patients with treatment-resistant depression, 35 with generalized anxiety disorder, and 21 with borderline personality disorder, as well as to 31 healthy volunteers. The Zung Self-rating Depression and Anxiety Scales were used to measure the respective depression and anxiety levels in these participants. RESULTS: All patients scored significantly higher on depression and anxiety than the healthy participants did. P3 amplitude was significantly reduced in groups with treatment-resistant depression and generalized anxiety disorder but not in the group with borderline personality disorder or healthy controls. Anxiety level was negatively correlated with P3 amplitude in healthy controls rather than in other groups. CONCLUSIONS: This study did not discriminate treatment-resistant depression and generalized anxiety disorder regarding the passive P3 but suggested that there was a generalized impairment of passive attention in these disorders.

Preliminary study of relationships between hypnotic susceptibility and personality disorder functioning styles in healthy volunteers and personality disorder patients.

BACKGROUND: Hypnotic susceptibility is one of the stable characteristics of individuals, but not closely related to the personality traits such as those measured by the five-factor model in the general population. Whether it is related to the personality disorder functioning styles remains unanswered. METHODS: In 77 patients with personality disorders and 154 healthy volunteers, we administered the Stanford Hypnotic Susceptibility Scale: Form C (SHSSC) and the Parker Personality Measure (PERM) tests. RESULTS: Patients with personality disorders showed higher passing rates on SHSSC Dream and Posthypnotic Amnesia items. No significant correlation was found in healthy volunteers. In the patients however, SHSSC Taste hallucination (ß=0.26) and Anosmia to Ammonia (ß=-0.23) were significantly correlated with the PERM Borderline style; SHSSC Posthypnotic Amnesia was correlated with the PERM Schizoid style (ß=0.25) but negatively the PERM Narcissistic style (ß=-0.23). CONCLUSIONS: Our results provide limited evidence that could help to understand the abnormal cognitions in personality disorders, such as their hallucination and memory distortions.

Mismatch negativity in treatment-resistant depression and borderline personality disorder.

OBJECTIVE: Cognitive dysfunctions, such as attentional impairment, are central features of both treatment-resistant depression (TRD) and borderline personality disorder (BPD). The treatment failure of TRD due to its comorbidity with BPD is debated in the literature. The mismatch negativity (MMN) of the event-related potentials provides an objective marker of involuntary stimulus selective processing, which might help shed light on this issue and provide an avenue for investigating a possible endophenotypic marker for TRD. METHOD: We investigated MMN in 22 patients with TRD, 19 with BPD, and 22 with TRD cormorbid with BPD (TRD+BPD), as well as in 32 healthy volunteers, by employing an acoustic frequency deviance paradigm. In addition, we measured the depressive mood using the Plutchik-van Praag (PVP) depression inventory. RESULTS: There was no significant between-group difference for the N1 latencies/amplitudes, both to the standard and deviant stimuli, and no significant between-group difference for MMN latencies. However, MMN amplitudes were higher in the TRD group than those in the other three groups. PVP scores were highest in TRD+BPD, then TRD, BPD patients, and lowest in healthy subjects. The higher MMN was not correlated with PVP score, nor with the duration of life-long depression, which can be considered as a neurophysiological marker for TRD. CONCLUSION: An atypical lack of inhibition on the irrelevant stimuli or increased cortical neuronal activity, especially frontal area, or both, might be responsible for the finding.