Totally laparoscopic resection of right-sided colon cancer using transvaginal specimen extraction with a 10-mm-long abdominal incision.

BACKGROUND: Natural orifice specimen extraction (NOSE) has been developed as a means of decreasing the incidence of surgical wound complications. We refined the procedure for totally laparoscopic colectomy with transvaginal specimen extraction using the reduced port surgery technique with the ultimate goal of attenuating damage to the abdominal wall. We herein report this innovative technique and its short- and long-term outcomes. METHODS: We prospectively collected data on seven patients who underwent totally laparoscopic colectomy using transvaginal specimen extraction with a 10-mm-long abdominal incision for right-sided colon cancer from January 2014 to December 2021. Two 5-mm ports were used in the procedure without laparotomy. Transverse transabdominal posterior colpotomy was then performed. We introduced a GelPOINT Mini advanced access platform (Applied Medical, Rancho Santa Margarita, CA, USA) into the transvaginal route for the insertion of a laparoscope, forceps, and stapling device. Lymph node dissection and transection of the ileum and distal colon were performed with transvaginal assistance. A specimen was then extracted transvaginally. Intracorporeal functional end-to-end anastomosis was conducted using a linear stapler through the vagina. After the removal of GelPOINT Mini, the vaginal incision was closed transvaginally. RESULTS: Seven patients successfully underwent this procedure. Median operative time was 219 min (range 174-255 min), median blood loss was 23 ml (range 10-37 ml), median number of harvested lymph nodes was 21 (range 17-35 lymph nodes) and median margins were 17.0 cm (range 9.0-25.0 cm) for the proximal margin and 9.5 cm (range 5.0-13.0 cm) for the distal margin. There were no complications more severe than Clavien-Dindo Grade II and there was no mortality. The median frequency of use intravenous analgesics from postoperative day 1 to discharge was once. Two patients did not require analgesics. A node-positive patient developed recurrence at the lung and paraaortic lymph nodes. CONCLUSIONS: This procedure appears to be feasible, safe, and oncologically acceptable for selected cases.

A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that has a pivotal role in adipocyte differentiation and expression of adipocyte-specific genes. The PPARgamma1 and gamma2 isoforms result from alternative splicing and have ligand-dependent and -independent activation domains. PPARgamma2 has an additional 28 amino acids at its amino terminus that renders its ligand-independent activation domain 5-10-fold more effective than that of PPARgamma1. Insulin stimulates the ligand-independent activation of PPARgamma1 and gamma2 (ref. 5), however, obesity and nutritional factors only influence the expression of PPARgamma2 in human adipocytes. Here, we report that a relatively common Pro12Ala substitution in PPARgamma2 is associated with lower body mass index (BMI; P=0.027; 0.015) and improved insulin sensitivity among middle-aged and elderly Finns. A significant odds ratio (4.35, P=0.028) for the association of the Pro/Pro genotype with type 2 diabetes was observed among Japanese Americans. The PPARgamma2 Ala allele showed decreased binding affinity to the cognate promoter element and reduced ability to transactivate responsive promoters. These findings suggest that the PPARgamma2 Pro12Ala variant may contribute to the observed variability in BMI and insulin sensitivity in the general population.

Development of the Nutrition and Functionality Assessment (NFA) among Older Adults in Japan.

OBJECTIVE: Develop and evaluate the feasibility and validity of the Nutrition and Functionality Assessment (NFA) which identifies "target" older adults who could benefit from a personalized program following evaluation of their nutrition status and physical functionality. DESIGN: Cross-sectional study. SETTING: Community and geriatric day-care centers and university in Japan. PARTICIPANTS: 267 older adults aged 65-90. MEASUREMENTS: The "target" individuals were screened based on gait speed (0.6-1.5 m/s). Nutrition (Mini Nutrition Assessment-short form and protein intake), strength (30s chair sit-to-stand and hand-grip strength) and endurance (6-minute walk) were assessed. Physical activity was monitored using a tri-axil accelerometer for a week. Fried frailty phenotype was also assessed. RESULTS: Out of 267 individuals, 185 (69%) had gait speed between 0.6-1.5 m/s, corresponding to our "target" group from which, 184 (95%) completed the nutrition and physical functionality assessments with the physical activity monitoring. The NFA was completed in approximately 30 minutes. No adverse events directly due to the NFA were reported. NFA physical functionality and global scores were significantly related to frailty phenotype but nutrition score was not related to frailty phenotype. CONCLUSION: The study demonstrated that the NFA is a safe and feasible tool to screen target older adults and simultaneously evaluate their nutritional status and physical functionality. Validity of the NFA was partially confirmed by the significant association of the global and physical functionality scores with frailty phenotype. More studies are required to validate and maximize the applicability of the NFA in communities and institutions in Japan and elsewhere.

Influence of duration of focal cerebral ischemia and neuronal nitric oxide synthase on translocation of apoptosis-inducing factor to the nucleus.

Translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus can play a major role in neuronal death elicited by oxidant stress. The time course of nuclear translocation of AIF after experimental stroke may vary with the severity of injury and may be accelerated by oxidant stress associated with reperfusion and nitric oxide (NO) production. Western immunoblots of AIF on nuclear fractions of ischemic hemisphere of male mice showed no significant increase with 1 h of middle cerebral artery occlusion and no reperfusion, whereas increases were detectable after 6 and 24 h of permanent ischemia. However, as little as 20 min of reperfusion after 1 h of middle cerebral artery occlusion resulted in an increase in nuclear AIF coincident with an increase in poly(ADP-ribose) polymer (PAR) formation. Further nuclear AIF accumulation was seen at 6 and 24 h of reperfusion. In contrast, 20 min of reperfusion after 2 h of occlusion did not increase nuclear AIF. In this case, nuclear AIF became detectable at 6 and 24 h of reperfusion. With brief occlusion of 30 min duration, nuclear AIF remained undetectable at both 20 min and 6 h and became evident only after 24 h of reperfusion. Inhibition of neuronal NO synthase attenuated formation of PAR and nuclear AIF accumulation. Gene deletion of neuronal NO synthase also attenuated nuclear AIF accumulation. Therefore, reperfusion accelerates AIF translocation to the nucleus when focal ischemia is of moderate duration (1 h), but is markedly delayed after brief ischemia (30 min). Nuclear translocation of AIF eventually occurs with prolonged focal ischemia with or without reperfusion. Neuronally-derived NO is a major factor contributing to nuclear AIF accumulation after stroke.

Immediate interlocking nailing versus external fixation followed by delayed interlocking nailing for Gustilo type IIIB open tibial fractures.

PURPOSE: To compare immediate interlocking nailing with external fixation followed by delayed interlocking nailing, for Gustilo type IIIB open tibial fractures. METHODS: 23 patients with Gustilo IIIB open tibial fractures were treated with either immediate unreamed interlocking nailing (n=9) or external fixation followed by delayed unreamed interlocking nailing (n=14). Patient age, sex ratio, fracture site, fracture type, and severity were similar in both groups. The time to union, deep infection rate, and nonunion rate in the 2 groups were compared. RESULTS: In the immediate and delayed nailing groups, respective mean times to union were 21 (standard deviation [SD], 14) months and 14 (SD, 8) months; nonunion rates were 44% (4/9) and 36% (5/14), and deep infection rates were 22% (2/9) and 7% (1/14). All corresponding differences were not statistically significant. CONCLUSION: Prospective, randomised, multicentre studies are needed to assess whether there are significant differences between the 2 treatment methods.

Computer-Assisted Detection of Cerebral Aneurysms in MR Angiography in a Routine Image-Reading Environment: Effects on Diagnosis by Radiologists.

BACKGROUND AND PURPOSE: Experiences with computer-assisted detection of cerebral aneurysms in diagnosis by radiologists in real-life clinical environments have not been reported. The purpose of this study was to evaluate the usefulness of computer-assisted detection in a routine reading environment. MATERIALS AND METHODS: During 39 months in a routine clinical practice environment, 2701 MR angiograms were each read by 2 radiologists by using a computer-assisted detection system. Initial interpretation was independently made without using the detection system, followed by a possible alteration of diagnosis after referring to the lesion candidate output from the system. We used the final consensus of the 2 radiologists as the reference standard. The sensitivity and specificity of radiologists before and after seeing the lesion candidates were evaluated by aneurysm- and patient-based analyses. RESULTS: The use of the computer-assisted detection system increased the number of detected aneurysms by 9.3% (from 258 to 282). Aneurysm-based analysis revealed that the apparent sensitivity of the radiologists' diagnoses made without and with the detection system was 64% and 69%, respectively. The detection system presented 82% of the aneurysms. The detection system more frequently benefited radiologists than being detrimental. CONCLUSIONS: Routine integration of computer-assisted detection with MR angiography for cerebral aneurysms is feasible, and radiologists can detect a number of additional cerebral aneurysms by using the detection system without a substantial decrease in their specificity. The low confidence of radiologists in the system may limit its usefulness.

Obesity and Muscle Weakness as Risk Factors for Mobility Limitation in Community-Dwelling Older Japanese Women: A Two-Year Follow-Up Investigation.

OBJECTIVES: To examine the combined association of obesity and low muscle strength with mobility limitation in older adults. DESIGN, SETTING AND PARTICIPANTS: This two-year follow-up longitudinal study included pooled data from 283 older community-dwelling Japanese women without mobility limitations who were 65 to 87 years of age (mean age 72.2 ± 5.0 years). MEASUREMENTS: Muscle strength was measured by hand-grip strength (HGS). The participants were categorized by HGS (high muscle strength: HGS ≥19.6 kg, low muscle strength: HGS <19.6 kg) and body mass index (BMI) (obese: BMI ≥25 kg/m2, normal weight: BMI <25 kg/m2). The main outcome was mobility limitation, assessed by a self-reported questionnaire (difficulty walking one-half mile or climbing 10 steps without resting). Multivariate logistic regression analysis was performed to determine the combined effect of HGS and BMI on mobility limitation, adjusting for age, exercise habits, medications, and knee pain. RESULTS: During the follow-up period, 82 of 283 participants (29.0%) developed mobility limitation. The adjusted odds ratios (95% confidence interval) for the incidence of mobility limitation were 1.53 (0.86-2.73) and 2.05 (1.08-3.91) in the obese and low muscle strength groups, respectively. Obesity combined with low muscle strength exhibited a significant and strong association with mobility limitation (odds ratio: 3.88, 1.08-13.91) compared with participants with normal weight and high muscle strength. CONCLUSION: Among community-dwelling older Japanese women, obesity alone was not associated with the incidence of mobility limitation, but when combined with low muscle weakness, the risk of developing mobility limitation was 3.9-fold greater than for the reference group.

The potential impact of a single amino-acid substitution on the efficacy of equine influenza vaccines.

REASONS FOR PERFORMING STUDY: The protection induced by an equine influenza (EI) vaccine strain depends on its antigenic relatedness to the challenge virus. Although the World Organisation for Animal Health (OIE) recommend that both Florida sublineage clade 1 (Fc1) and clade 2 (Fc2) viruses should be included in EI vaccines, Japanese EI vaccines have not, thus far, been updated to include a Fc2 virus. OBJECTIVES: To evaluate the efficacy of antibodies raised against Japanese EI vaccine strains in the neutralisation of recent Fc2 viruses. STUDY DESIGN: Antigenic analysis. METHODS: Virus neutralisation tests were performed using antisera from experimentally infected horses and from horses that had received a primary course of the currently available vaccines. RESULTS: Antiserum raised against the Japanese EI vaccine strain, A/equine/La Plata/1993, exhibited poor cross-neutralising activity against the Fc2 viruses isolated recently in Ireland and the UK, which have the substitution of alanine to valine at position 144 in antigenic site A of the haemagglutinin gene. In contrast, the antiserum exhibited good cross-neutralising activity against the Fc2 viruses without the substitution. This finding was supported in experiments with antisera collected from vaccinated horses. CONCLUSIONS: This suggests that the efficacy of the Japanese EI vaccine for some of the recent Fc2 viruses is suboptimal and that vaccines should be updated in accordance with the OIE recommendations.

Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: dynamic changes in hemoglobin concentration and oxygenation.

The origins of reflected light changes associated with neuronal activity (optical signals) were investigated in rat somatosensory cortex with optical imaging, microspectrophotometry, and laser-Doppler flowmetry, and dynamic changes in local hemoglobin concentration and oxygenation were focused on. Functional activation was carried out by 2-second, 5-Hz electrical stimulation of the hind limb under chloralose anesthesia. These measurements were performed at the contralateral parietal cortex through a thinned skull. Regional cortical blood flow (rCBF) started to rise 1.5 seconds after the stimulus onset, peaked at 3.5 seconds (26.7% +/- 9.7% increase over baseline), and returned to near baseline by 10 seconds. Optical signal responses at 577, 586, and 805 nm showed a monophasic increase in absorbance coincident with the increase in rCBF; however, the signal responses at 605 and 760 nm were biphasic (an early increase and late decrease in absorbance) and microanatomically heterogeneous. The spectral changes of absorbance indicated that the concentrations of both total hemoglobin and oxyhemoglobin increased together with rCBF; deoxyhemoglobin, increased slightly but distinctly (P = 0.016 at 1.0 seconds, P = 0.00038 at 1.5 seconds) just before rCBF increases, then decreased. The authors conclude that activity-related optical signals are greatly associated with a moment-to-moment adjustment of rCBF and metabolism to neuronal activity.

Implications of phosphoinositide 3-kinase in the mu- and delta-opioid receptor-mediated supraspinal antinociception in the mouse.

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that activates signalling pathways. The present study was designed to investigate whether PI3K could be involved in supraspinal antinociception induced by intracerebroventricular (i.c.v.) administration of micro- and delta-opioid receptor agonists in the mouse. We demonstrated using the mouse warm-plate assay that the prototype of micro-opioid receptor agonist morphine, selective mu-opioid receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO) and delta-opioid receptor agonists [D-Ala(2)]deltorphin II and [D-Pen(2,5)]enkephalin (DPDPE) when given i.c.v. produced profound antinociceptive responses. Under these conditions, i.c.v. pretreatment with cell-permeable and specific PI3K inhibitors wortmannin (0.7-2.3 nmol) and LY294002 (3-33 nmol), which alone had no effects on the basal warm-plate latencies, caused a dose-dependent inhibition of either morphine-, DAMGO-, DPDPE- or [D-Ala(2)]deltorphin II-induced antinociception. Furthermore, LY294002 at 33 nmol significantly shifted the dose-response curves for DAMGO-, DPDPE- and [D-Ala(2)]deltorphin II-induced antinociception to the right. In the immunoblotting assay, we found that PI3K gamma is dense in the periaqueductal gray and lower medulla regions that include several key sites for the production of opioid-induced antinociception. Our findings provide evidence that central PI3K pathways may, at least in part, contribute to the expression of supraspinal antinociception induced by both mu- and delta-opioid receptor agonists in the mouse.

Pirfenidone prevents collagen accumulation in the remnant kidney in rats with partial nephrectomy.

Pirfenidone (PFD) is a new compound that prevents and even reverses the extracellular matrix accumulation in several organs as shown by experimental and clinical studies. In the present study, we examined the effect of PFD (500 mg/kg daily in the food) on the progression of chronic renal failure (CRF) in the 5/6 nephrectomy rat model. Proteinuria progressively increased in rats with renal ablation (C) at 12 weeks. Urinary protein excretion in PFD-treated rats (P) was numerically lower than C, but the difference did not reach statistical significance. In contrast, in the chronic phase, PFD improved renal function and reduced collagen accumulation detected by hydroxyproline content (OH-Pro) in the cortex of the remnant kidney. Although creatinine clearance decreased with time in C, the values in P were significantly better at 10 and 12 weeks. The OH-Pro in C at 12 weeks was significantly higher than that of no-ablation, sham-operated rats, whereas OH-Pro in CRF was lower in (P). Expression of mRNA for type IV and I collagen in the cortex also increased in C, but it was inhibited in (P). To study the role that TGF-beta plays in the regulatory process following CRF, we examined the expression of TGF-beta mRNA in this model. Levels of cortical TGF-beta mRNA in C were significantly elevated at 12 weeks. The increase was suppressed by PFD. These results demonstrate that PFD attenuates the development of CRF by preventing collagen accumulation in this model, and suggest that PFD can be clinically useful for treating CRF.

Regulation of serotonin transporter gene expression in human glial cells by growth factors.

The aims of this study were to identify monoamine transporters expressed in human glial cells, and to examine the regulation of their expression by stress-related growth factors. The expression of serotonin transporter mRNA was detected by reverse transcriptase-polymerase chain reaction in normal human astrocytes, whereas the dopamine transporter (DAT) and the norepinephrine transporter (NET) were not detected. The cDNA sequence of the "glial" serotonin transporter in astrocytes was consistent with that reported for the "neuronal" serotonin transporter (SERT). Moreover, we also demonstrated SERT expression in glial fibrillary acidic protein-positive cells by immunocytochemical staining in normal human astrocytes. Serotonin transporter gene expression was also detected in glioma-derived cell lines (A172, KG-1-C and KGK). Addition of basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) for 2 days increased serotonin transporter gene expression in astrocytes and JAR (human choriocarcinoma cell line). Basic fibroblast growth factor, but not epidermal growth factor, increased specific [3H]serotonin uptake in astrocytes in a time (1-4 days)- and concentration (20-100 ng/ml)-dependent manner. The expression of genes for basic fibroblast growth factor and epidermal growth factor receptors was detected in astrocytes. These findings suggest that the expression of the serotonin transporter in human glial cells is positively regulated by basic fibroblast growth factor.

Effects of CP-99, 994, a tachykinin NK(1) receptor antagonist, on abdominal afferent vagal activity in ferrets: evidence for involvement of NK(1) and 5-HT(3) receptors.

The effect of CP-99, 994, a tachykinin NK(1) receptor antagonist, on abdominal vagal afferent nerve activity in the ferret was investigated. Substance P (1 microg/kg, i.v.) increased vagal afferent activity by 449.0+/-51.9% and this was reduced to 145.9+/-5.7% (p<0.01) by pre-treatment with CP-99, 994 (1 mg/kg, i.v.), and to 149.5+/-1.5% (p<0.001) by granisetron (1 mg/kg, i.v.), a 5-HT(3) receptor antagonist. In addition, the increase in vagal nerve activity induced by 5-HT (25 microg/kg, i.v., 552.0+/-57.0% increase from pre-injection level) was significantly reduced (401.3+/-10.6% increase from pre-injection level, p<0.05) by CP-99, 994 (100 microg/kg, i.v.). These results provide evidence for an involvement of peripheral NK(1) and 5-HT(3) receptors in substance P-induced vagal afferent activation. While the functional consequences (if any) of such peripheral effects were not investigated, they could contribute either directly (e.g. by blockade of receptors on vagal afferents) or indirectly (e.g. modulation of 5-HT release or reduction of local inflammatory response) to the antiemetic effects of CP-99, 994 against cisplatin and other emetic agents acting primarily via the vagus.

Neuroepithelial (colloid) cyst of the cerebellar vermis containing a xanthogranuloma.

A case of a neuroepithelial cyst of the cerebellar vermis is presented. The cyst contained a viscous fluid and a xanthogranulomatous nodule. The fluid showed high signal on T1- and low signal on T2-weighted MR images. The xanthogranuloma showed mixed intensities with partial contrast enhancement. The correlation of the cyst contents and MR signals is discussed.

Exchange transfusion with fluorocarbon for studying synaptically evoked optical signal in rat cortex.

Optical imaging of intrinsic signal is a powerful technique for studying the functional organization of the brain [T. Bonhoeffer, D. S. Kim, D. Malonek, D. Shoham, A. Grinvald, Optical imaging of the layout of functional domains in area 17 and across the area 17/18 border in cat visual cortex, Eur. J. Neurosci. 7 (1995) 1973-1988; M. Hubener, D. Shoham, A. Grinvald, T. Bonhoeffer, Spatial relationships among three columnar systems in cat area 17, J. Neurosci. 17 (1997) 9270-9284; D. Malonek, A. Grinvald, Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping, Science 272 (1996) 551-554; A. Shmuel, A. Grinvald, Functional organization for direction of motion and its relationship to orientation maps in cat area 18, J. Neurosci. 16 (1996) 6945-6964] [1] [10] [14] [22]. Three components of intrinsic optical signal can be distinguished. Two of these components can be attributed either to changes in blood volume or to changes in oxygen consumption [R.D. Frostig, E.E. Lieke, D.Y. Ts'o, A. Grinvald, Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high resolution optical imaging of intrinsic signals, Proc. Natl. Acad. Sci. U. S. A. 87 (1990) 6082-6086] [7]. The origin of the third component is not yet clear but the component seems to be based on scattered light [H.U. Dodt, G. D'Arcangelo, E. Pestel, W. Zieglgansberger, The spread of excitation in neocortical columns visualized with infrared-dark field videomicroscopy, NeuroReport 7 (1996) 1553-1558; K. Holthoff, O.W. Witte, Intrinsic optical signals in rat neocortical slices measured with near-infrared dark-field microscopy reveal changes in extracellular space, J. Neurosci. 16 (1996) 2740-2749; B.A. MacVicar, D. Hochman, Imaging of synaptically evoked intrinsic optical signals in hippocampal slices, J. Neurosci. 11 (1991) 1458-1469; L. Trachsel, H.U. Dodt, W. Zieglgansberger, The intrinsic optical signal evoked by chiasm stimulation in the rat suprachiasmatic nuclei exhibits GABAergic day-night variation, Eur. J. Neurosci. 8 (1996) 319-328] [3] [9] [13] [24]. A spectral fitting method with three components is used for the analysis of intrinsic optical signal [M. Nemoto, Y. Nomura, C. Sato, M. Tamura, K. Houkin, I. Koyanagi, H. Abe, Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: dynamic changes in hemoglobin concentration and oxygenation, J. Cereb. Blood Flow Metab. 19 (1999) 246-259] [17]. In order to validate the analysis, we need the knowledge on contribution of signal resulted from hemoglobin to total intrinsic optical signal. The exchange transfusion with fluorocarbon has the advantage that can change the spectral contribution of hemoglobin [M. Ferrari, M.A. Williams, D.A. Wilson, N.V. Thakor, R.J. Traystman, D.F. Hanley, Cat brain cytochrome-c oxidase redox changes induced by hypoxia after blood-fluorocarbon exchange transfusion, Am. J. Physiol. 269 (1995) H417-H424; A.L. Sylvia, C.A. Piantadosi, O(2) dependence of in vivo brain cytochrome redox responses and energy metabolism in bloodless rats, J. Cereb. Blood Flow Metab. 8 (1988) 163-172] [6] [23]. Here we describe a new method of the reduction of hemoglobin signal from somatosensory evoked optical intrinsic signal in rat cortex by the combination of exchange transfusion with fluorocarbon and imaging system of thinned skull cranial window. The method allows for the study of the synaptically evoked changes in light scattering as well as fluorescence of calcium indicator or voltage-sensitive dye without absorption of hemoglobin.

Pathogenesis of vascular dementia in stroke-prone spontaneously hypertensive rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) are the best model for essential hypertension and stroke. In this study, one investigated whether SHRSP might be a useful animal model for vascular dementia. An impairment of learning-memory function was found in SHRSP. A disturbance in circadian rhythm after stroke in SHRSP was clarified. Desynchronization of light and dark alternation cycles and abnormal rhythm were also demonstrated. These observations point to the possibility that the decreased passive avoidance response observed in SHRSP might be similar to the phenomenon of memory impairment in patients with vascular dementia. The behavioral changes in ambulation in SHRSP, including the desynchronization between light and dark alternation cycles and the abnormal rhythm before death, might correspond to the behavioral changes associated with the delirium-state observed in patients with dementia. Cerebral cortex levels of acetylcholine and choline in SHRSP decreased significantly as compared with the Wistar Kyoto rats (WKY) control group. Hippocampal levels of acetylcholine and choline in SHRSP decreased significantly as compared with those in WKY. Moreover, a correlation between passive avoidance response latency and hippocampal acetylcholine levels was observed. These findings suggest that decreased acetylcholine levels in both the cerebral cortex and the hippocampus may be related to the impairment of learning-memory function and abnormal behavior. In SHRSP, increases in blood viscosity, hematocrit and fibrinogen might produce the formation of thrombus and induce cerebral infarction. Some histopathological findings caused by cerebrovascular disorder in human brain very similar to those observed in the SHRSP brain. On the other hand, so called 'senile changes' were detected only in the human case, and not observed in the SHRSP.

Neurochemistry and neuropharmacology of emesis - the role of serotonin.

Emesis is an instinctive defense reaction caused by the somato-autonomic nerve reflex which is integrated in the medulla oblongata. Emesis caused by cytotoxic drugs and radiation is associated with an increase in the concentration of 5-hydroxytryptamine (5-HT) in the intestinal mucosa and in the brainstem. 5-HT released from enterochromaffin (EC) cells, which synthesize and secrete 5-HT, stimulates the 5-HT(3) receptors on the adjacent vagal afferent nerves. This vagal afferent nerve depolarization may evoke the vomiting reflex. This review describes the role of 5-HT in anticancer drug-induced emesis from the viewpoint of 5-HT release from EC cells and afferent vagus nerve activity.

Evaluation of serum uric acid changes in different forms of hepatic vascular inflow occlusion in human liver surgeries.

Uric acid values in serum have been analyzed as one of the markers to predict cellular damage due to ischemia reperfusion injury in the field of organ transplantation. The present study was conducted to confirm that uric acid values in serum could be an efficient marker of ischemic injury of liver parenchyma following hepatic vascular occlusion in human liver surgery. The changes in serum uric acid values were analyzed at fixed intervals during different liver surgeries. Significant increases in serum uric acid values were observed in patients who received the Pringle's maneuver in which hepatic vascular inflow was manipulated with a repetition of 15 min occlusion and 5 min perfusion, whereas almost no changes in uric acid values were found in both groups of patients who received the hemilobal occlusion of the Glisson's triad in which the right or left vessels were manipulated with a repetition of 30 min occlusion and 5 min perfusion and the "control method" in which the hepatic vessels of the lesion side were previously cut before liver resection. Uric acid values in serum increased in patients of Pringle's maneuver compared to those of the hemilobal occlusion of the Glisson's triad and the control method though these procedures were used in larger hepatectomies rather than Pringle's maneuver. The results indicated that serum uric acid values do not always reflect the severity of ischemia of the liver parenchyma but reflect intestinal congestion because marked intestinal congestion was observed in patients of Pringle's maneuver but not in patients of the hemilobal occlusion of the Glisson's triad and the control method. The evaluation of the severity of the ischemic injury of the liver should be done with caution when uric acid is used as a marker in human liver surgery.

Induction of metallothionein and stimulation of calcification by dexamethasone in cultured clonal osteogenic cells, MC3T3-E1.

To clarify the effects of dexamethasone (Dex) on metallothionein (MT) synthesis and calcification in osteoblastic cells, a clonal osteogenic cell line (MC3T3-E1) was used in the present study. Under culture conditions designed not to cause calcification, MT synthesis of cells at 3 days after inoculation increased with increasing concentration of Dex (2.5-50 nM) for a 24-h culture period. Cells at 6 or 9 days after inoculation also synthesized MT by a 24-h exposure to Dex. These show that undifferentiated osteoblasts have the ability to synthesize MT by Dex. Under culture conditions designed to cause calcification, cells at 6 days after inoculation were cultured with 50 nM Dex in the presence of 7 mM beta-glycerophosphate (beta-GP) for 7 days. Ca content of Dex-treated cells was about 7.5 times as high as that of untreated cells. Dex-treated cells showed a high activity of alkaline phosphatase (ALP). The Zn content of the MT fraction in Dex-treated cells was about 8 times as high as that of untreated cells. These results show that Dex has the ability to induce MT synthesis in osteoblastic cells and to cause a high calcification which is due at least partly to an enhanced activity of ALP.

Delayed inactivation of Citrobacter freundii cephalosporinase by 6 beta-[3-(2-chlorophenyl)-5-methyl-4-isoxazolyl]penicillin sulfone.

When Citrobacter freundii cephalosporinase was incubated with 6 beta-[3-(2-chlorophenyl)-5-methyl-4-isoxazolyl]penicillin sulfone (cloxacillin sulfone) in phosphate buffer, the enzyme was suddenly inactivated just after the completion of enzymatic degradation of the cloxacillin sulfone. Such delayed inactivation was due to a secondary inhibitor formed from cloxacillin sulfone during the incubation period. The inactivation was delayed due to the protection of the enzyme by cloxacillin sulfone from the attack of the secondary inhibitor. Phosphate anions were essential for the formation of the secondary inhibitor. However, once the secondary inhibitor was formed, the inactivation occurred in the absence of phosphate anions although the degree of the inactivation depended on the length of the preincubation period with phosphate anions. The main species (more than 80%) of the inactivated enzyme was detected as a single protein band with a slightly lower pI value than that of the native enzyme on isoelectric focusing on a plate.