Efficacy of percutaneous ethanol injection therapy (PEIT) is related to the number of parathyroid glands in haemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: Percutaneous ethanol injection therapy (PEIT) is used for advanced secondary hyperparathyroidism. We investigated the efficacy, remission period and risk of relapse to determine the effect of the number of hyperplastic glands and other factors on the therapeutic effect of PEIT. METHODS: We studied 321 patients divided into two groups: effective [serum corrected calcium (cCa) level < or =10.5 mg/dl and serum intact parathyroid hormone (iPTH) level < or =250 pg/ml], and ineffective (failed to achieve the target levels). Advanced hyperplasia was defined as an estimated volume > or =0.5 cm(3) on ultrasonography. RESULTS: PEIT was effective in 201 patients (62.6%), in whom serum iPTH levels dropped from 603+/-292 to 183+/-62 pg/ml (ng/l) and serum cCa levels from 10.7+/-0.8 to 10.1+/-0.5 mg/dl. Univariate analysis identified age, the number of hyperplastic glands and iPTH level as factors related to the efficacy of PEIT. The odds ratio for success vs failure by multivariate analysis was 0.55 times for the number of hyperplastic glands > or =0.5 cm(3) (> or =2 vs 0,1) and 0.29 times for iPTH (> or =500 vs <500 pg/ml). Using the Kaplan-Meier method, the number of hyperplastic glands > or =0.5 cm(3) (> or =2 vs 0,1) was a factor affecting the remission period, with a remission significantly longer seen in the group with one hyperplastic gland (P=0.0025). CONCLUSIONS: Superior results in efficacy rate, remission period and risk of relapse are obtained when PEIT is restricted to patients with one hyperplastic gland > or =0.5 cm(3).     

Successful ultrasonically guided percutaneous ethanol injection for secondary hyperparathyroidism.

Ultrasonically guided percutaneous ethanol injection to all of four enlarged parathyroid glands, which were confirmed by fine-needle aspiration biopsy, was successfully performed in a hemodialysis patient with secondary hyperparathyroidism. In addition to marked reduction of serum parathyroid hormone, the size of parathyroid glands was significantly decreased after the procedure. As an adverse effect, the patient experienced a transient self-limiting dysphonia due to right recurrent nerve palsy after the first injection. This procedure may be an effective alternative to surgical treatment or administration of high-dose 1,25(OH)2 vitamin D3 in uremic patients with sonographically verified multiple enlarged parathyroid glands.     

Dietary diacylglycerol induces the regression of atherosclerosis in rabbits

Recent studies of the relation between serum triacylglycerol concentration and the risk for coronary artery disease suggest that inefficient clearance of postprandial triacylglycerols promotes atherogenesis. We recently demonstrated that dietary diacylglycerol (DAG), rich in the 1,3-species, suppresses the postprandial increase in serum triacylglycerol levels compared with dietary triacylglycerol (TAG). Here, we investigated the effects of dietary DAG on atherosclerosis in rabbits with cholesterol-induced atherosclerosis. New Zealand White rabbits (n = 20) were fed a diet containing 3% lard and 1.3% cholesterol for 50 d to induce atherosclerotic lesions. Thereafter, the rabbits were assigned to 2 groups and fed 90 g/d nonpurified diet and orally administered 5 g DAG or TAG for an additional 34 d. Reference rabbits (n = 5) were fed only the nonpurified diet throughout the 84-d study. The area of atherosclerotic lesions and aortic lipid concentrations were significantly lower in DAG-fed rabbits compared with TAG-fed rabbits. The VLDL receptor and macrophage antigen-1 mRNA expression levels were significantly lower in DAG-fed rabbits than in TAG-fed rabbits. In the liver of DAG-fed rabbits, the triacylglycerol concentration was lower and the carnitine palmitoyltransferase activity higher than in TAG-fed rabbits. Stimulation of hepatic lipid catabolism might be related to the reduced lipid accumulation in the liver and aorta by reducing the release of triacylglycerol into the circulation. Thus, long-term consumption of DAG, which reduces postprandial lipemia, might be useful for the regression of atherosclerosis by stimulating hepatic lipid catabolism and thereby modulating monocyte/macrophage migration and aortic lipid accumulation.     

High-dose granulocyte-colony stimulating factor promotes neointimal hyperplasia in the early phase and inhibits neointimal hyperplasia in the late phase after vascular injury

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) affects injured arteries through early endothelialization. Some reports, however, have cautioned that the restenosis rate may increase after G-CSF injection. In the present study, high-dose G-CSF was administered to mice with vascular injury to clarify its effect. METHODS AND RESULTS: Mice were received daily subcutaneous injections of saline or a high dose (300 microg/kg) of G-CSF for 5 days after vascular injury. In the FACS analysis, CD34-/Sca-1-positive progenitor cells were more abundant in the G-CSF group (p<0.05). Neointimal hyperplasia was more evident in the G-CSF group at 1 week (p<0.05), whereas at 4 weeks it was more evident in the control group (p<0.01). TUNEL-positive cells in the arterial wall were more numerous in the G-CSF group at day 1 (p<0.01). CD34-positive cells were observed in the G-CSF group at 1 week. Re-endothelialization appeared earlier in the G-CSF group (at 4 weeks; p<0.01). An increased number of 1A4-positive smooth muscle cells were found in bone marrow cell culture treated with G-CSF. CONCLUSION: High-dose G-CSF induced neointimal proliferation through excessive inflammation and bone marrow cell mobilization in the early phase. In the late phase, however, it induced early re-endothelialization and thereby inhibited neointimal hyperplasia.     

Bi-level positive airway pressure ventilation for treating heart failure with central sleep apnea that is unresponsive to continuous positive airway pressure.

BACKGROUND: Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is associated with a poor prognosis in patients with heart failure (HF). However, some patients do not respond to continuous positive airway pressure (CPAP), so other therapeutic modalities should be considered, such as bi-level positive airway pressure (PAP), which also assists respiration and might be effective for such patients. METHODS AND RESULTS: The 20 patients with HF because of left ventricular systolic dysfunction were assessed: 8 had ischemic etiology, and all had severe CSA according to the apnea - hypopnea index (AHI) determined by polysomnography. All diagnosed patients underwent repeat polysomnography using CPAP. The AHI improved significantly in 11 (AHI <15), but only slightly in 9, in whom the AHI remained high (>or=15). Bi-level PAP titration significantly improved the AHI in the latter group. Those who were unresponsive to CPAP had significantly lower PaCO(2), higher plasma brain natriuretic peptide (BNP), longer mean duration of CSR and fewer obstructive episodes than CPAP responders. After 6 months of positive airway support with either CPAP (n=9) or bi-level PAP (n=7), BNP levels significantly decreased and left ventricular ejection fraction significantly increased. CONCLUSIONS: Bi-level PAP could be an effective alternative for patients with HF and pure CSR-CSA who are unresponsive to CPAP.     

Coronary Artery Disease Severity and Cardiovascular Biomarkers in Patients with Peripheral Artery Disease

Cardiovascular mortality in peripheral artery disease (PAD) patients is higher in critical limb ischemia (CLI) than in intermittent claudication (IC). We sought to evaluate differential characteristics of coronary artery disease (CAD) severity and prognostic biomarkers for cardiovascular events between CLI and IC patients. Coronary angiography was performed on 242 PAD patients (age 73 ± 8 years) with either CLI or IC. High-sensitivity troponin T (hs-TnT), eicosapentaenoic acid–arachidonic acid ratio (EPA/AA), and lipoprotein(a), as biomarkers for prognostic factors, were measured from blood samples. The study patients were divided into a CLI-group (n = 42) and IC-group (n = 200). The Gensini score as an indicator of coronary angiographic severity was higher in the CLI-group than in the IC-group (39.1 ± 31.2 vs. 8.5 ± 8.3, p < 0.0001). Hs-TnT and lipoprotein(a) values were higher in the CLI-group than in the IC-group (0.152 ± 0.186 ng/mL vs. 0.046 ± 0.091, p < 0.0001, 45.9 ± 23.3 mg/dL vs. 26.2 ± 27.7, p = 0.0002, respectively) and EPA/AA was lower in the CLI-group than in the IC-group (0.22 ± 0.11 vs. 0.38 ± 0.29, p = 0.0049, respectively). Greater CAD severity, higher hs-TnT, and lipoprotein(a), and lower EPA/AA were observed in the CLI-group, which may explain higher cardiovascular events in patients with CLI.     

Network mechanisms of hippocampal laterality,place coding,and goal-directed navigation

The hippocampus and associated structures are responsible for episodic memory in humans. In rodents, the most prominent behavioral correlate of hippocampal neural activity is place coding, which is thought to underlie spatial navigation. While episodic memory is considered to be unique to humans in a restricted context, it has been proposed that the same neural circuitry and algorithms that enable spatial coding and navigation also support episodic memory. Here we review the recent progress in neural circuit mechanisms of hippocampal activity by introducing several topics: (1) cooperation and specialization of the bilateral hippocampi, (2) the role of synaptic plasticity in gamma phase-locking of spikes and place cell formation, (3) impaired goal-related activity and oscillations in a mouse model of mental disorders, and (4) a prefrontal-thalamo-hippocampal circuit for goal-directed spatial navigation.     

Role of PKA signaling in D2 receptor-expressing neurons in the core of the nucleus accumbens in aversive learning

The nucleus accumbens (NAc) serves as a key neural substrate for aversive learning and consists of two distinct subpopulations of medium-sized spiny neurons (MSNs). The MSNs of the direct pathway (dMSNs) and the indirect pathway (iMSNs) predominantly express dopamine (DA) D1 and D2 receptors, respectively, and are positively and negatively modulated by DA transmitters via Gs- and Gi-coupled cAMP-dependent protein kinase A (PKA) signaling cascades, respectively. In this investigation, we addressed how intracellular PKA signaling is involved in aversive learning in a cell type-specific manner. When the transmission of either dMSNs or iMSNs was unilaterally blocked by pathway-specific expression of transmission-blocking tetanus toxin, infusion of PKA inhibitors into the intact side of the NAc core abolished passive avoidance learning toward an electric shock in the indirect pathway-blocked mice, but not in the direct pathway-blocked mice. We then examined temporal changes in PKA activity in dMSNs and iMSNs in behaving mice by monitoring Förster resonance energy transfer responses of the PKA biosensor with the aid of microendoscopy. PKA activity was increased in iMSNs and decreased in dMSNs in both aversive memory formation and retrieval. Importantly, the increased PKA activity in iMSNs disappeared when aversive memory was prevented by keeping mice in the conditioning apparatus. Furthermore, the increase in PKA activity in iMSNs by aversive stimuli reflected facilitation of aversive memory retention. These results indicate that PKA signaling in iMSNs plays a critical role in both aversive memory formation and retention.Aversive stimuli induce not only rapid avoidance behavior, but also memory formation to escape from uncomfortable environments, and thus strongly influence animal behavior (1–3). The mesolimbic dopaminergic (DA) system plays a critical role in both rapid aversive reaction and memory formation (3–5). The nucleus accumbens (NAc) receives DA inputs from the ventral tegmental area (VTA) and serves as a key neural substrate for the control of aversive learning (6–8). The NAc consists of two subpopulations of medium-sized spiny neurons (MSNs) (9–11). The MSNs of the direct pathway (dMSNs) send their axons to the substantia nigra pars reticulata (SNr) and VTA, and selectively express dopamine D1 receptors, whereas the MSNs of the indirect pathway (iMSNs) indirectly project to the SNr and VTA via the ventral pallidum (VP) and predominantly express D2 receptors (12, 13). D1 receptors stimulate the cAMP-dependent protein kinase A (PKA) signaling cascade via Gs and exhibit a low affinity for DA (14–16). Conversely, D2 receptors inhibit the cAMP-PKA cascade via Gi and show a high affinity for DA (14–16). Thus, these two distinct types of MSNs, constituting two parallel pathways, contribute to the dynamic modulation of neuronal cell excitability and synaptic plasticity in the NAc circuitry (14–16).Although accumulated evidence indicates that DA modulation of the NAc is critical for both reward-based and aversive reactions (3, 5, 6, 17), the response of DA neurons in the VTA to aversive stimuli is not uniform; that is, some DA neurons are stimulated in response to aversive stimuli, whereas most others react by transiently suppressing their firing (18–22). Recent optogenetic studies have revealed that not only activation of iMSNs, but also inactivation of the VTA neurons, which down-regulates DA levels in the NAc, evoke an aversive reaction and learning (23–26); however, how intracellular cAMP-PKA signaling is involved in the induction and retention of aversive memory in a cell type-dependent manner in the NAc circuit remains largely elusive.In the present investigation, we addressed this issue using two approaches. We first used asymmetric reversible neurotransmission blocking (aRNB) techniques (27, 28), in which either the direct or indirect pathway at one side of the NAc was selectively blocked by the pathway-specific expression of transmission-blocking tetanus toxin and the other intact side was manipulated by injection of PKA inhibitors. In the second approach, we examined temporal changes in PKA activities of these two pathways in the formation of aversive memory by monitoring Förster resonance energy transfer (FRET) responses of PKA selective for either dMSNs or iMSNs with the aid of in vivo microendoscopic analysis (29, 30). These two different approaches explicitly demonstrated that the activation of PKA in iMSNs plays a key role in both the formation and the retention of aversive memory.     

Laparoscopic resection of a gastrointestinal stromal tumor of the rectum after treatment with imatinib mesylate: report of a case

This report describes the laparoscopic resection of a rectal GIST after treatment with imatinib mesylate. A 56-year-old male presented with a submucosal tumor (longest diameter, 8?cm) arising in the lower rectum. A core needle biopsy revealed that the tumor contained bundles of spindle-like cells. Immunostaining revealed that the tumor was positive for c-kit and CD34. Analysis of the c-kit gene revealed a substitution of ACA (threonine) by GCA (alanine) at codon 574 of exon 11. Imatinib mesylate (400?mg/day) was given as preoperative adjuvant therapy for 3?months, and the tumor shrank to 5?cm in diameter. Proctectomy with transanal anastomosis could be performed laparoscopically, while preserving the anus. There was no evidence of recurrence 2?years 6?months after surgery. Preoperative adjuvant chemotherapy with imatinib mesylate may permit the use of less invasive treatment procedures, allowing anal preservation.