Selective decline in protein F1 phosphorylation in hippocampus of senescent rats

Certain forms of neuronal plasticity have been found to be expressed through alterations in brain protein phosphorylation, and its regulation by protein kinase activity. Of interest in this regard is the possibility that the decline in neuronal plasticity and cognitive function that occurs in advanced age may result in part from altered phosphorylation of specific proteins. As a first attempt to identify age-related changes in phosphoproteins, we assayed in vitro phosphorylation of proteins in hippocampus, cerebellum, entorhinal cortex, and frontal cortex from Fischer-344 rats of 5 months, 11 months, and 25 months of age. Compared to the middle-aged animals, the aged rats showed a selective 46% decline in phosphorylation of the 47 kDa protein (F1) in hippocampus, with no change in the phosphorylation of other proteins measured in this structure. Aged animals also showed decreased phosphorylation relative to young animals. No age-related change was observed in any protein band for the other brain areas examined. Since protein F1 is phosphorylated by protein kinase C (PKC), the cytosolic and membrane distribution of this enzyme was compared across age groups. The activity of PKC in hippocampus did not change across age. The explanation of this age-related decline in protein F1 phosphorylation is likely to be a decline in the substrate protein itself. The results are discussed in terms of protein F1's possible role in age-related decline of hippocampal synaptic plasticity.     

A DLST genotype associated with reduced risk for Alzheimer's disease

Recent studies suggest that variants of the DLST gene alter the risk of AD. DLST encodes the core subunit of the mitochondrial alpha-ketoglutarate dehydrogenase complex, which is deficient in AD. The authors report that in 247 US white subjects, homozygosity for DLST A19,117, T19,183 was associated with a reduced risk of AD (odds ratio [OR] = 0.35, p = 0.018). The reduced risk was marked in subjects who did not carry the apolipoprotein (APOE)-4 allele (OR = 0.16, p = 0.014). Further study of DLST in AD appears warranted.     

Current role of local ablative treatments for hepatocellular carcinoma.

Due to modern diagnostic imaging and the sensitive alpha-fetoprotein test, small hepatocellular carcinoma can now be detected at an early stage. Studies have shown that surgical resection of the tumors is a valuable treatment. Local treatment under ultrasound guidance was initially considered as an alternative when patients' liver reserves were not good enough for surgical resection; however, this technique has been improved and the results indicate that its survival rate can compete with that of surgical resection. In follow-up studies of patients with small hepatocellular carcinoma, a 5-year survival of 60% has been achieved after percutaneous ethanol injection therapy. Percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation therapy have been shown to have some advantages over percutaneous ethanol injection therapy, although the follow-up durations of these studies were not long enough. Percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation therapy have become the 3 most widely used techniques for the treatment of hepatocellular carcinomas that are less than 5 cm in diameter and have a tumor number less than 3. In general, a tumor size of 3 to 5 cm is a good candidate for radiofrequency ablation and a tumor size of 2 to 3 cm is suitable for radiofrequency ablation or microwave coagulation. If the tumor size is around 2 cm or less, microwave coagulation or ethanol injection is often chosen due to the relatively low cost and similar efficacy. Ethanol injection also has the advantage of needing only a fine needle for injection. Informed selection of the appropriate technique, or combining a technique with transcatheter hepatic arterial embolization according to the tumor size and number, might provide the most effective treatment and achieve better results for hepatocellular carcinoma, even if the liver reserve is not good. However, large-scale, randomized, controlled trials are required before a definitive conclusion can be reached.     

Percutaneous microwave coagulation therapy under ultrasound guidance for small hepatocellular carcinoma.

BACKGROUND AND PURPOSE: Percutaneous microwave coagulation therapy (PMCT) can effectively treat hepatocellular carcinomas (HCCs) smaller than 2 cm. However, for tumors 2 to 3 cm in size, combination of transarterial chemoembolization (TACE) or multiple insertions of electrodes may be more effective. This study investigated the treatment efficacy of PMCT for tumors 2 to 3 cm in size. METHODS: Nineteen HCCs smaller than 3 cm in diameter (< 2 cm in 11, and 2-3 cm in 8) in 18 patients (including 14 previously treated patients) were treated by PMCT under ultrasound guidance. One or 2 PMCT electrodes were consecutively inserted either into the left and right portion, or into the distal and proximal portion of the tumor, according to the size, shape, and margin of tumors and puncture direction. Liver function tests and contrast-enhanced computed tomography were used to examine preoperative status and response to PMCT. RESULTS: After an average of 1.6 emissions of PMCT, 18 tumors (95%) were completely ablated. The only case of treatment failure was due to a tumor location which made the approach of the electrode difficult. Bacteremia developed after the procedure in 1 patient (5%) and local inflammatory reaction of the puncture wound in another (5%). During follow-up ranging from 5 to 19 months, no recurrence was noted at the site of the original tumors. Tumor recurrence was detected at another site 2-9 months after PMCT in 9 of the 14 previously treated patients. CONCLUSION: PMCT can effectively and safely treat HCCs smaller than 3 cm in size without combination of TACE or multiple insertions of electrodes.     

Laparoscopic-assisted vaginal hysterectomy with in situ morcellation for large uteri

STUDY OBJECTIVE: To estimate whether laparoscopic in situ morcellation (LISM) can facilitate laparoscopic-assisted vaginal hysterectomy (LAVH) for large uteri. DESIGN: Prospective study (Canadian Task Force classification II-1). SETTING: University-affiliated hospital. PATIENTS: In all, 147 women with myoma or adenomyosis weighing more than 500 g from January 2004 through December 2007 were enrolled. The patients were divided into 4 subgroups: patients with uteri weighing 500 to 749 g who had traditional LAVH without LISM (group 1A, n = 69) or with LISM (group 1B, n = 16); and patients with uteri weighing 750 g or more who were treated by traditional LAVH without LISM (group 2A, n = 38) or with LISM (group 2B, n = 24). INTERVENTIONS: Laparoscopic-assisted vaginal hysterectomy with or without LISM. MEASUREMENT AND MAIN RESULTS: No significant differences existed in age, body mass index, preoperative diagnoses, complications, or duration of hospital stay among groups. The mean uterine weights were 608 +/- 75, 597 +/- 66, 989 +/- 179, and 935 +/- 226 g for groups 1A, 1B, 2A, and 2B, respectively. The operative time (120 +/- 16 vs 157 +/- 36 minutes, p <.001; 140 +/- 19 vs 224 +/- 57 minutes, p <.001) were significantly shorter in patients with LISM than without in both groups 1 and 2. The estimated blood loss was highest in group 2A. Six (16%) patients lost more than 500 mL of blood and 3 (8%) of them needed blood transfusions. Conversion to laparotomy occurred in 1 (2.6%) of 38 patients in group 2A. No repeated surgery or surgical mortality occurred. CONCLUSION: Laparoscopic-assisted vaginal hysterectomy with LISM was an efficient and safe procedure for removal of large uteri during LAVH.     

Anti-inflammatory cembranoids from the soft corals Sinularia querciformis and Sinularia granosa

Four new cembranoids, querciformolides A-D (1-4), along with two known cembranoids, 7 and 8, have been isolated from the soft coral Sinularia querciformis. Furthermore, chemical investigation of Sinularia granosa has afforded three new cembranoids, querciformolide B (2) and granosolides A (5) and B (6). The structures of the new metabolites were elucidated on the basis of extensive spectroscopic methods, and that of 2 was further confirmed by X-ray diffraction analysis. The absolute configurations of 1 and 2 were determined by a modified Mosher's method. Among these metabolites, 2-6 are rarely found cembranoids possessing a tetrahydrofuran moiety with a 4,7-ether linkage; in addition, 1 is the first epsilon-lactone cembrane found that possesses a tetrahydropyran moiety with a 4,8-ether linkage. None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. However, compounds 3, 7, and 8 significantly inhibited the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.     

Twenty-minute pad test: comparison of infusion of 250 ml of water with strong-desire amount in the bladder in women with stress urinary incontinence

OBJECTIVE: The objective was to compare the sensitivity of the 20-min pad test by infusion of 250 ml of water with the strong-desire amount in the bladder in women with stress urinary incontinence (SUI). STUDY DESIGN: Eighty-three women with SUI were enrolled between November 2005 and January 2006. The 20-min pad test by infusion of 250 ml of water was performed before urodynamic study (UDS). The strong-desire amount pad test was done after UDS. The results were analyzed by Pearson's chi(2) and Wilcoxon's signed-rank tests. RESULTS: The sensitivity by infusion of the strong-desire amount was better than infusion of 250 ml of water in the 20-min pad test (P<0.001). In the quantitative study, the two pad tests had fair agreement and the pad weight results of the infusion of the strong-desire amount were statistically higher than the infusion of 250 ml of water (P=0.0004). CONCLUSIONS: The infusion of the strong-desire amount had better sensitivity measured by the 20-min pad test in women with SUI compared with infusion of 250 ml of water in the bladder.     

Comparison of recurrence rates after anterior colporrhaphy for cystocele using three different surgical techniques

AIMS: To compare the recurrence rates after anterior colporrhaphy for cystocele using three different surgical techniques: standard plicating, purse-string, and rolling anterior colporrhaphy. METHODS: A retrospective chart review of women undergoing anterior colporrhaphy for cystocele with or without concomitant operations between 1988 and 2000 was conducted. Women were assessed by vaginal examination pre- and postoperatively at 6 weeks and over 2 years. Grades of cystocele were assessed by Baden-Walker halfway grading system. chi(2) tests and ANOVAs were performed for categorical and continuous variables, respectively. Cox regressions were used to calculate recurrent rates. RESULTS: Among the studied 363 women, 296, 33, and 34 underwent standard plicating, purse-string and rolling techniques, respectively. There was no significant difference in age, parity, menopausal status, or mean length of follow-up among the three groups. The purse-string group revealed a significantly higher risk of recurrence than the standard plicating group (hazard ratio: 2.67; 95% CI: 1.05-6.08). The severity of cystocele was another key role of determining the prognosis for recurrences (grades 3 & 4 relative to grade 1, hazard ratio: 3.35; 95% CI: 1.34-8.38). CONCLUSION: Our study showed that standard plicating and rolling technique provided similar anatomic cure rates. However, the purse-string technique was less effective in restoring vaginal anatomy than standard plicating anterior colporrhaphy.     

Changes of brachial flow-mediated vasodilation in different ischemic stroke subtypes

The relationship between endothelial dysfunction and stroke subtypes is unclear. We prospectively measured brachial flow-mediated vasodilation (FMD) in 143 patients with acute ischemic stroke and 40 controls. The overall stroke patients had impaired FMD, but only lacunar infarction had significantly impaired FMD vs the controls. Impaired FMD was an independent predictor for lacunar infarction. Ischemic stroke is associated with endothelial dysfunction, which is more conspicuous in lacunar infarction.