In Vivo AAV1 Transduction With hRheb(S16H) Protects Hippocampal Neurons by BDNF Production

Recent evidence has shown that Ras homolog enriched in brain (Rheb) is dysregulated in Alzheimer''s disease (AD) brains. However, it is still unclear whether Rheb activation contributes to the survival and protection of hippocampal neurons in the adult brain. To assess the effects of active Rheb in hippocampal neurons in vivo, we transfected neurons in the cornu ammonis 1 (CA1) region in normal adult rats with an adeno-associated virus containing the constitutively active human Rheb (hRheb(S16H)) and evaluated the effects on thrombin-induced neurotoxicity. Transduction with hRheb(S16H) significantly induced neurotrophic effects in hippocampal neurons through activation of mammalian target of rapamycin complex 1 (mTORC1) without side effects such as long-term potentiation impairment and seizures from the alteration of cytoarchitecture, and the expression of hRheb(S16H) prevented thrombin-induced neurodegeneration in vivo, an effect that was diminished by treatment with specific neutralizing antibodies against brain-derived neurotrophic factor (BDNF). In addition, our results showed that the basal mTORC1 activity might be insufficient to mediate the level of BDNF expression, but hRheb(S16H)-activated mTORC1 stimulated BDNF production in hippocampal neurons. These results suggest that viral vector transduction with hRheb(S16H) may have therapeutic value in the treatment of neurodegenerative diseases such as AD.     

Characteristics and Treatment Outcomes of Isoniazid Mono-Resistant Tuberculosis: A Retrospective Study

PurposeIsoniazid (INH) mono-resistant tuberculosis (Hr-TB) is a highly prevalent type of drug-resistant TB, possibly associated with unfavorable treatment outcomes. However, definitive guidelines on an optimal treatment regimen and duration for Hr-TB are currently under discussion. We evaluated the characteristics and treatment outcomes of Hr-TB patients.Materials and MethodsWe retrospectively reviewed the medical records of Hr-TB patients treated at a South Korean tertiary referral hospital from January 2005 to December 2018.ResultsWe included 195 Hr-TB patients. 113 (57.9%) were male, and the median age was 56.6 [interquartile range, 40.2–68.6] years. Mutations in katG were the most frequent [54 (56.3%)], followed by those in the inhA [34 (35.4%)]. Favorable and unfavorable outcomes were noted in 164 (84.1%) and 31 (15.9%) patients, respectively. Smoking history [odds ratio (OR)=5.606, 95% confidence interval (CI): 1.695–18.543, p=0.005], low albumin level (OR=0.246, 95% CI: 0.104–0.578, p=0.001), and positive acid-fast bacilli culture at 2 months (OR=7.853, 95% CI: 1.246–49.506, p=0.028) were associated with unfavorable outcomes.ConclusionA tailored strategy targeting high-risk patients is imperative for improved treatment outcomes. Further research on the rapid and accurate detection of resistance to INH and other companion drugs is warranted.     

Symptomatic subependymoma--a case report

Subependymoma is a rare, slow-growing, benign noninvasive tumor of the central nervous system that may be located in the fourth ventricle, the septum pellucidum, the third and the lateral ventricles, the aqueduct, and the proximal spinal cord. Symptoms, if any, usually result either from direct compression of the brain stem or from acute hydrocephalus due to occlusion of the foramen of Monro or aqueduct of Sylvius. In this report, we describe a case of subependymoma of the lateral ventricle with headache in a young female patient. This is the first reported case subependymoma in Korea that was documented along with Magnetic resonance image.     

Variations in urinary 1-hydroxypyrene glucuronide in relation to smoking and the modification effects of GSTM1 and GSTT1.

The measurement of the pyrene metabolite, 1-hydroxypyrene, in human urine has been used to assess recent exposure to polycyclic aromatic hydrocarbons (PAH). The objective of this study was to see whether genetic polymorphisms in metabolic enzymes could explain some of the variation in urinary 1-hydroxypyrene glucuronide (1-OHPG) excretion in relation to smoking. Forty-seven male hospital workers, who were not occupationally exposed to PAH, participated in this study. The urine samples were analyzed for 1-OHPG utilizing immunoaffinity chromatography and synchronous fluorescence spectroscopy. The analysis of GSTM1 and GSTT1 polymorphism was performed by PCR. The 1-OHPG concentration in the urine of the hospital workers was 0.57 +/- 0.85 micromol/mol creatinine, and ranged from 0.02 to 5.04 mciromol/mol creatinine. Cigarette smoking was significantly correlated with urinary 1-OHPG (r = 0.3976, P = 0.0056). The 1-OHPG excretion in GSTM1-deficient smokers was higher than that in GSTM1-positive smokers. On the other hand, 1-OHPG excretion was higher in GSTT1-positive smokers than in GSTT1-deficient smokers. It is important to note the variability of individual PAH metabolite excretion due to different GSTM1 and GSTT1 genotypes.     

Mechanical and heat sensitization of cutaneous nociceptors in rats with experimental peripheral neuropathy

This study examined whether or not the properties of cutaneous nociceptive fibers are altered in the neuropathic state by comparing lumbars 5 and 6 spinal nerve ligation (SNL) rats with sham-operated controls. The rats with the unilateral SNL developed mechanical allodynia in the ipsilateral hind limb, whereas the sham group did not. Two to 5 weeks after the neuropathic or sham surgery, rats were subjected to single fiber-recording experiments to examine the properties of afferent fibers in the sural and plantar nerves. A total of 224 afferents in the C- and Adelta-ranges were characterized in the neuropathic and sham groups. Spontaneous activity was observed in 16 of 155 fibers in the neuropathic group and one of 69 fibers in the sham group. The response threshold of both the C- and Adelta-fibers to mechanical stimuli was lower in the neuropathic group than the sham group. The afferent fibers responsive to heat stimuli were all C-fibers, and none were Adelta-fibers. The response threshold of the C-fibers to the heat stimuli was lower in the neuropathic group than the sham group. The magnitude of the responses of both C- and Adelta-fibers to the suprathreshold intensity of the mechanical stimulus was greater in the neuropathic group than the sham group. However, the magnitude of the responses of C-fibers to the suprathreshold intensity of the heat stimulus in the neuropathic group was not different from that in the sham group. These results suggest that after a partial peripheral nerve injury, the nociceptors on the skin supplied by an uninjured nerve become sensitized to both mechanical and heat stimuli. This nociceptor sensitization can contribute to neuropathic pain.     

Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia

Based on the use of Scutellaria baicalensis for the treatment of stroke in traditional Oriental medicine, the current study was carried out to evaluate neuroprotective effects of S. baicalensis after transient global ischemia using rat 4-vessel occlusion model. Methanol extracts from the dried roots of S. baicalensis (0.1-10 mg/kg) administered intra-peritoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. Methanol extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production, and protected PC12 cells from hydrogen peroxide-induced toxicity in vitro.