Investigation of mechanisms mediating 8-OH-DPAT-induced impairment of spatial memory: involvement of 5-HT1A receptors in the dorsal hippocampus in rats

The purpose of this study was to identify mechanisms that mediate the impairment of spatial memory induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A/5-HT7 receptor agonist, in the eight-arm radial maze in rats. WAY-100635 and NAN-190, 5-HT1A receptor antagonists, reversed the impairment of spatial memory induced by systemic injection of 8-OH-DPAT (1 mg/kg, i.p.). On the other hand, the alpha1-adrenoceptor antagonist prazosin and a selective 5-HT7 receptor antagonist SB269970 had no effect on 8-OH-DPAT-induced impairment of spatial memory. Bilateral microinjection of 8-OH-DPAT (4 microg/side) impaired spatial memory when injected into the dorsal hippocampus (DH). Contrastingly, spatial memory was unaffected by microinjections of 8-OH-DPAT into the other six areas examined: ventral hippocampus (VH), central amygdaloid nucleus (ACE), lateral hypothalamus (LH), nucleus accumbens (NAc), and dorsal (DR) and median (MR) raphe nucleus. Furthermore, NAN-190 significantly reversed the impairment of spatial memory induced by intra-DH injection of 8-OH-DPAT. These findings suggest that 5-HT1A receptors in the DH play an important role in the mechanisms underlying the 8-OH-DPAT-induced impairment of spatial memory in rats.     

Acetazolamide acts directly on the human skeletal muscle chloride channel

Acetazolamide, a carbonic anhydrase inhibitor, is used empirically in neuromuscular diseases with episodic ataxia, weakness, and myotonia, although not all of the mechanisms responsible for its therapeutic effects are understood. To elucidate whether acetazolamide acts directly on the human skeletal muscle voltage-gated chloride channel (ClC-1), which is associated with myotonia, we evaluated the effects of acetazolamide on ClC-1 expressed in cultured mammalian cells, using whole-cell recording. Acetazolamide significantly shifted the voltage dependency of the open probability (P(o)) toward negative potentials in a dose-dependent manner, resulting in an increase of chloride conductance at voltages near the resting membrane potential. This effect was attenuated when using a pipette solution containing 30 mmol/L Hepes. These results suggest that acetazolamide can influence the voltage-dependent opening gate of ClC-1 through a mechanism related to intracellular acidification by inhibiting carbonic anhydrase, and that the therapeutic effects of acetazolamide in neuromuscular diseases may be mediated by activation of ClC-1.     

Nonuniformity of sarcomere shortenings in the isolated rat ventricular myocyte

By projecting the image of a single ventricular myocyte upon a linear image sensor, the striation pattern was analyzed during resting and contracting states. During rest, the individual cycle length (ICL) of the striation pattern varied from 1.8 to 2.0 microm within a given cell. ICL measured every 2 ms fluctuated approximately 0.05 microm around the mean. The variance of temporal fluctuations was decreased by chelating the extracellular Ca(2+) and increased by the Ca(2+) overload. Blocking the Ca(2+) release channels with 10 micromol/l ryanodine reversed this increase. In the power spectral density, an increase in the power occurred in the frequency range below 10 Hz. This increase should reflect overall kinetics of both intracellular Ca(2+) handling and responses of contractile filaments, because the same pattern was observed when spontaneous contractions occurred as well as when contractions were evoked by activating the L-type Ca(2+) channels. It is suggested that the temporal fluctuations of ICL in the resting state are caused by spontaneous Ca(2+) release from ryanodine receptors on the sarcoplasmic reticulum. Furthermore, under evoked contractions the shortenings of ICL were spatially inhomogeneous. These findings of nonuniform sarcomere shortenings are consistent with the temporal and spatial inhomogeneity of Ca(2+) transients.     

Delayed-onset temporary auditory threshold shift following head blow in guinea pigs

This study attempts to investigate the development of sensorineural hearing loss following a head blow without skull fracture in association with physiological and histopathologic changes in an experimental animal model. With the head in a freely movable position, albino guinea pigs were given a single blow to the occipital region by a head blow device. At 1, 7, and 14 days after the blow, the animals' auditory brainstem response (ABR) and cochlear microphonics (CM) were examined, and both the temporal bone and brain stem were observed by light and electron microscopy. The ABR threshold was unchanged at day 1, was significantly increased at day 7, and was fully recovered at day 14. The I-V and I-II interpeak latencies were significantly prolonged at days 1 and 7, and wave I latency was significantly prolonged at day 7 only. These latencies were recovered to normal limits at day 14. On the other hand, no significant change in CM versus the control group was observed at any point in the measurements. Histopathologically, no abnormal finding was seen at the light microscopic level. However, at the electron microscopic level, there were some injuries to the eighth nerve. At day 1, the lamellar structure of the myelin sheath was irregular, and the periaxonal space was expanded; at day 7, the myelin sheath was disintegrated. At day 14, however, these changes were partially reversed. These results suggest that sensorineural hearing loss following a head blow in this model is attributed to dysfunction of the eighth nerve rather than to cochlear impairment.     

Hexokinase-II expression in untreated oral squamous cell carcinoma: Comparison with FDG PET imaging

Hexokinase is thought to be one of the key factors of glucose catabolism in the cell. The aim of this study was to investigate the relationship between HK-II expression and 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in human untreated oral squamous cell carcinoma (OSCC). Pre-operatively FDG positron emission tomography (PET) was performed 60 min after FDG injection in all the patients. Maximum standardized uptake value (SUV) was used for evaluation of tumor FDG uptake. Tumor sections were stained immunohistochemically for HK-II. All the tumor sections stained positive for HK-II. Eighteen (95%) tumors in HK-II showed immunostained positive area >50%. HK-II findings revealed eleven (58%) tumors with strong intensity, six (32%) with moderate intensity and two with weak intensity (10%). There was no statistically significant correlation between SUV and the expression of HK-II (p = 0.46). In conclusion, OSCC showed increased FDG accumulation and overexpression of HK-II. However, we did not find any significant relationship between high FDG uptake and overexpression of HK-II in this patient population, and thus other properties need to be evaluated in order to elucidate key factors responsible for FDG activity in OSCC.     

Laparoscopic hepatectomy with the hook blade of ultrasonic coagulating shears and bipolar cautery with a saline irrigation system

Background The number of patients who have undergone laparoscopic hepatectomy is small, and the operative procedure is not yet well established.Methods We performed laparoscopic hepatectomy in eight patients, using the hook blade of ultrasonic coagulating shears, and bipolar cautery with a saline irrigation system, with minilaparotomy. The operative time, blood loss, and postoperative hospital stay of patients with laparoscopic left lateral segmentectomy were compared with these parameters in ten patients who had had a left lateral segmentectomy with laparotomy.Results The laparoscopic hepatectomies included seven left lateral segmentectomies and one nonanatomical partial resection of the lateral segment. The mean duration of the operation in these eight patients was 181.1 ± 44.6min. The mean amount of blood loss was 177.6 ± 129.1ml. Postoperative complications consisted of two cases of bleeding. The mean postoperative hospital stay in all eight patients was 9.88 ± 4.36 days. The mean duration of operation (185.9 ± 46.0min) and mean postoperative hospital stay (9.47 ± 4.61 days) in the seven patients with laparoscopic left lateral segmentectomies were significantly shorter than these parameters (255.7 ± 59.4min and 24.6 ± 8.82 days) in the ten patients who had had left lateral segmentectomies with laparotomy. The mean amount of blood loss (160.0 ± 128.9ml) in the laparoscopic series was less than that (318.5 ± 192.2 days) in the patients who had had laparotomy.Conclusions Laparoscopic hepatectomy with the ultrasonic coagulating shears and bipolar cautery with minilaparotomy was safe, and less invasive than the open procedure, for minor hepatectomy procedures such as left lateral segmentectomy.     

Establishment of rat model of acute staphylococcal osteomyelitis: relationship between inoculation dose and development of osteomyelitis

Introduction Many animal models of acute and chronic osteomyelitis have been developed. In these models, osteomyelitic lesions are induced using sclerosing agents and foreign bodies with bacterial strains. In the present rat model, these sclerosing agents were not used. We assessed the relationship between inoculation dose and histological, radiological, and microbiological changes in the acute phase (1 week after inoculation) using this rat osteomyelitis model.Materials and methods An experimental rat model of acute osteomyelitis was developed by direct inoculation of the virulent strain BB of Staphylococcus aureus into tibial bone without sclerosants. To examine the relationship between the inoculation dose of the bacteria and the progression of the osteomyelitis, the inoculated lesions were assessed for changes in histological, radiological, and bacteriological parameters at 1 week after infection. Serial dilutions of the bacteria [6×10¹ to 6×10⁵ colony-forming units (CFU)/5 l] suspended in saline or saline alone were inoculated into the proximal metaphysis of the tibia.Results Development of significant histological and radiological signs of osteomyelitis required an inoculum of at least 6×10³ CFU/5 l. The number of viable bacteria at the lesion reached a maximum of 6×10³ CFU/5 l.Conclusion These results suggest that strain BB induces the development of acute staphylococcal osteomyelitis with clear infective destruction in the tibia, and that our model may be applied to the identification of virulence factors in studies of posttraumatic osteomyelitis.