Background
Ketamine is a commonly used anesthetic but the mechanistic basis for its clinically relevant actions remains to be determined. We previously showed that HCN1 channels are inhibited by ketamine and demonstrated that global HCN1 knockout mice are two-fold less sensitive to hypnotic actions of ketamine. Although that work identified HCN1 channels as a viable molecular target for ketamine, it did not determine the relevant neural substrate.
Methods
To localize the brain region responsible for HCN1-mediated hypnotic actions of ketamine, we employed a conditional knockout strategy to delete HCN1 channels selectively in excitatory cells of the mouse forebrain. A combination of molecular, immunohistochemical and cellular electrophysiological approaches was used to verify conditional HCN1 deletion; a loss-of-righting reflex assay served to ascertain effects of forebrain HCN1 channel ablation on hypnotic actions of ketamine.
Results
In conditional knockout mice, HCN1 channels were selectively deleted in cortex and hippocampus, with expression retained in cerebellum. In cortical pyramidal neurons from forebrain-selective HCN1 knockout mice, effects of ketamine on HCN1-dependent membrane properties were absent; notably, ketamine was unable to evoke membrane hyperpolarization or enhance synaptic inputs. Finally, the half maximal effective concentration (EC50) for ketamine-induced loss-of-righting reflex was shifted to significantly higher concentrations (by ~31%).
Conclusions
These data indicate that forebrain principal cells represent a relevant neural substrate for HCN1-mediated hypnotic actions of ketamine. We suggest that ketamine inhibition of HCN1 shifts cortical neuron electroresponsive properties to contribute to ketamine-induced hypnosis.
Acne vulgaris is a common skin condition in adolescents. The prevalence of acne is thought to vary between ethnic groups and countries. A large-scale community-based study was performed in six cities in China to determine the prevalence and possible risk factors for acne in the Chinese population. A total of 17,345 inhabitants were included in this study. Of these, 1,399 were found to have acne. No acne was found in subjects under 10 years of age, and only 1.6% in the 10-year-old group had acne. Prevalence then increased rapidly with age, up to 46.8% in the 19-year-old group. After that, it declined gradually with age. Acne was rare in people over 50 years of age. In subjects in their late teens and 20s, acne was more prevalent in males, while in those over 30 years of age it was more prevalent in females. In subjects with acne, 68.4% had mild; 26.0% had moderate and 5.6% had severe acne. In adult acne, persistent acne was much more common (83.3%) than late-onset acne (16.7%). Smoking and drinking were found to be associated with adolescent acne, while no association was found between diet and acne. These results suggest that the prevalence of acne in the Chinese population is lower than that in Caucasian populations, and that adult acne is not uncommon in Chinese subjects.
Vitiligo is a common skin disease, the prevalence of which varies between races and countries. In China, no population-based study has been reported, although there have been some epidemiological studies on single cities or regions. The objective of this study was to obtain the prevalence and clinical profile of vitiligo in China. The study was conducted in 6 cities. Cluster sampling was used in selecting communities. Residents were visited at home and were asked to complete questionnaires and receive dermatological examinations. A total of 19,974 residents were visited and 17,345 valid questionnaires were obtained. The overall prevalence of vitiligo was 0.56%. Men were affected more than women (0.71% vs. 0.45%, p < 0.01). The prevalence of vitiligo increased with age. The most common type was focal vitiligo (36.1%). A positive family history was found in 9.8% of patients. Thirty-two percent of patients reported a negative impact of vitiligo on their quality of life.
In our screening program for insecticidal activity of the essential oils/extracts derived from some Chinese medicinal herbs and spices, garlic (Allium sativum L.) essential oil was found to possess strong insecticidal activity against overwintering adults of Cacopsylla chinensis Yang et Li (Hemiptera: Psyllidae). The commercial essential oil of A. sativum was analyzed by gas chromatography-mass spectrometry. Sixteen compounds, accounting for 97.44% of the total oil, were identified, and the main components of the essential oil of A. sativum were diallyl trisulfide (50.43%), diallyl disulfide (25.30%), diallyl sulfide (6.25%), diallyl tetrasulfide (4.03%), 1,2-dithiolane (3.12%), allyl methyl disulfide (3.07%), 1,3-dithiane (2.12%), and allyl methyl trisulfide (2.08%). The essential oil of A. sativum possessed contact toxicity against overwintering C. chinensis, with an LC50 value of 1.42 microg per adult. The two main constituent compounds, diallyl trisulfide and diallyl disulfide, exhibited strong acute toxicity against the overwintering C. chinensis, with LC50 values of 0.64 and 11.04 /g per adult, respectively.
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