Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

Electrical stimulation of the medial prefrontal cortex increases dopamine release in the striatum

Exogenous and endogenous glutamate has been shown to evoke dopamine (DA) release in the striatum using both in vitro and in vivo techniques. We hypothesized that stimulation of the prefrontal cortex (PFC) would phasically enhance striatal DA release via the glutamatergic corticostriatal pathway. To test this hypothesis, in vivo brain microdialysis was employed to measure extracellular concentrations of DA in the striatum during electrical stimulation of the PFC. Five rats were implanted with bilateral electrodes located in the medial PFC and dialysis probes in the dorsal striatum. Two days later the PFC of these awake, freely moving rats was stimulated first at 50 microA and then at 100 microA for 20 minutes at 2-hour intervals. Both currents significantly increased DA release. Extracellular DA rose rapidly during stimulation, peaked immediately afterward, and then slowly returned to baseline values. Dopamine reached 118% of baseline values with 50 microA stimulation and 138% with 100 microA stimulation. Histologic analysis using the fluorescent retrograde dye Fluoro Gold confirmed that cells projecting to the vicinity of the striatal dialysis probe originated in the vicinity of the PFC electrodes. These results provide direct evidence for phasic, excitatory modulation of striatal DA release by the PFC.     

Long-term follow-up (8 to 17 years) after thromboexclusion operation for thoracic aortic aneurysms

Forty-eight Russell's viper bite patients (40 males, 8 females), age ranging from 16-76 years were studied. Out of 48 patients, 14 were found to have a prolonged whole blood clotting time test (WBCT) (i.e. incoagulable blood) (Group 1); 23 had a normal WBCT (i.e. clotted blood) (Group II); and 11 patients had a normal WBCT on admission which changed to non-clotting during the clinical course (Group III). Four patients from group I developed hypotension and 2 expired. The serum cortisol concentration (mean +/- SEM) on admission among groups I and II were 639 +/- 45.6 and 424 +/- 33.2 nmol/l respectively. The blood cortisol level in 35 subjects (controls) were 370.7 +/- 17.7 nmol/l (mean +/- SEM). There was a significant rise of blood cortisol in patients with incoagulable blood when compared to controls at the time of admission to the hospital (p < 0.05); but there was no significant difference among those patients with clotted blood. A much higher mean serum cortisol level was observed in 4 patients with hypotension as compared to 10 patients without shock. These patients with hypotension according to our study shown to have a favorable response to steroid therapy and eventually recovered. Whether higher doses of steroid in addition to antiserum confer extra benefit in suppressing nonspecific venom effects on the pituitary and/or adrenal is not known.     

The directional effects of passive eye movement on the directional visual responses of single units in the pigeon optic tectum

We have investigated the visual responses of 184 single units located in the superficial layers of the optic tectum (OT) of the decerebrate, paralysed pigeon. Visual responses were similar to those reported in non-decerebrate preparations; most units responded best to moving visual stimuli, 18% were directionally selective (they had a clear preference for a particular direction of visual stimulus movement), 76% were plane-selective (they responded to movement in either direction in a particular plane). However, we also found that a high proportion of units showed some sensitivity to the orientation of visual stimuli. We examined the effects of extraocular muscle (EOM) afferent signals, induced by passive eye movement (PEM), on the directional visual responses of units. Visual responses were most modified by particular directions of eye movement, although there was no unique relationship between the direction of visual stimulus movement to which an individual unit responded best and the direction of eye movement that caused the greatest modification of that visual response. The results show that EOM afferent signals, carrying information concerning the direction of eye movement, reach the superficial layers of the OT in the pigeon and there modify the visual responses of units in a manner that suggests some role for these signals in the processing of visual information.     

Treatment of hypertension in nondiabetic renal disease

To clarify whether long-term impaired glucose tolerance (IGT) is associated with dysfunction of peripheral and autonomic nerves, age-matched men with IGT and diabetes mellitus were followed prospectively for 12-15 years, when peripheral and autonomic nerve function was assessed. The patients comprised four subgroups: (1) 51 IGT subjects (duration of IGT at least 12-15 years); (2) 35 diabetic patients, with IGT 12-15 years ago, who later developed diabetes; (3) 34 diabetic patients, duration of diabetes at least 12-15 years; and (4) 62 age-matched non-diabetic control subjects. Mean age of the whole study population was 61 +/- 2 years (mean +/- SD), not different in the four groups. Peripheral nerve function tests included nerve conduction velocities, amplitudes, distal latencies, F-reflexes, and sensory perception thresholds for heat, cold, and vibration. Autonomic nerve function tests included the heart rate reaction during deep breathing (expiration to inspiration ratio) and to tilt (acceleration and brake indices). Despite 12-15 years of IGT, peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio (a sign of vagal nerve dysfunction) was significantly more common (15/51 versus 5/62; p < 0.01) in IGT than in control subjects. Diabetic patients (groups 2 and 3) showed lower conduction velocities (in general 2-4 m s-1 lower) than IGT and control subjects in all tested nerves. In conclusion, diabetes but not IGT, is associated with peripheral nerve dysfunction.     

Acidity and basicity of hydrotalcite derived mixed Mg-Al oxides studied by test reaction of MBOH conversion and temperature programmed desorption of NH3 and CO2

Mg-Al hydrotalcites intercalated with five different interlayer anions—CO₃²⁻, SO₄²⁻, Cl⁻, HPO₄²⁻ or terephthalate—were synthesized by either the coprecipitation or ion-exchange method. The structure of the as-synthesized samples and the presence of intended anions in the interlayer gallery of hydrotalcites were determined by X-ray diffraction and FTIR spectroscopy. On calcination at 600 °C the materials were transformed into mixed metal oxides. The kind of the counterbalancing anions present in the parent hydrotalcite influences strongly textural parameters of the obtained Mg-Al oxides. Both temperature-programmed desorption of NH₃ and CO₂, and test reaction of 2-methyl-3-butyn-2-ol (MBOH) conversion were used to determine the acidity and basicity of the samples. The hydrotalcite derived mixed Mg-Al oxides showed the presence of Brønsted and Lewis acid and base sites. However, the strong basic character of the solids caused that acetone and acetylene were observed as the major products of MBOH conversion.