Interaction of nicotinic acetylcholine receptors with dopamine receptors in synaptic plasticity of the mouse insular cortex

The insular cortex plays essential roles in nicotine addiction. However, much is still unknown about its cellular and synaptic mechanisms responsible for nicotine addiction. We have previously shown that in layer 5 pyramidal neurons of the mouse insular cortex, activation of the nicotinic acetylcholine receptors (nAChRs) suppresses synaptic potentiation through enhancing GABAergic synaptic transmission, although it enhances both glutamatergic and GABAergic synaptic transmission. In the present study, we examined whether dopamine receptors might contribute to the nicotine‐induced inhibition of synaptic potentiation. The nicotine‐induced inhibition of synaptic potentiation was decreased in the presence of a D1 dopamine receptor antagonist SCH23390 irrespective of the presence of a D2 dopamine receptor antagonist sulpiride, suggesting that D1 dopamine receptors are involved in nicotine‐induced inhibition. We also investigated how dopamine receptors might contribute to the nAChR‐induced enhancement of glutamatergic and GABAergic synaptic transmission. The nAChR‐induced enhancement of GABAergic synaptic transmission was decreased in the presence of SCH23390 irrespective of the presence of sulpiride, whereas that of glutamatergic synaptic transmission was not altered in the presence of SCH23390 and sulpiride. These results suggest that D1 dopamine receptors are involved in the nAChR‐induced enhancement of GABAergic synaptic transmission while dopamine receptors are not involved in that of glutamatergic synaptic transmission. These observations indicate that the interaction between nAChRs and D1 dopamine receptors plays critical roles in synaptic activities in layer 5 pyramidal neurons of the mouse insular cortex. These insular synaptic changes might be associated with nicotine addiction.     

Effect of Induction Therapy Protocols on Transplant Outcomes in Crossmatch Positive Renal Allograft Recipients Desensitized with IVIG

Here we retrospectively examine the efficacy of two antibody induction regimens using Zenapax or Thymoglobulin in patients with positive complement-dependent cytotoxicity crossmatches (CDC-CMXs) desensitized with IVIG (intravenous immunoglobulin). Between January 1999 and March 2005, 97 patients with (+) CDC-CMXs received kidney transplants (43 deceased donors/54 living donors). All patients received at least 2 g/kg IVIG (maximum four doses) until an acceptable CMX was obtained. Patients were divided into two groups: 1. IVIG + Zenapax (n = 58), 2. IVIG + Thymoglobulin (n = 39). A total of 94% of patients in Group 1 and 84% in G2 have at least 2 years of follow up. Patient and graft survival was 96%/84% in Group 1 and 100%/90% in Group 2, p = NS. The number and severity of AR episodes were similar (36% Group 1 vs. 31% Group 2, p = NS) as was the incidence of C4d (+) antibody-mediated rejection (AMR) (Banff Grade II/III) (22% Group 1 vs. 21% Group 2). Mean serum creatinines (SCrs) at 24 months were similar (Group 1: 1.4 +/- 0.7 vs. G2: 1.5 +/- 0.7 mg/dL). Induction therapy with Zenapax or Thymoglobulin results in excellent patient, graft survival and graft function at 2 years. There was no increased risk of viral infections or malignancies with either agent. Neither agent was effective in reducing the incidence of AMR.     

Acute Immobilization Stress and Intraventricular Injection of CRF Suppress Naloxone-Induced LH Release in Ovariectomized Estrogen-Primed Rats

The present study was undertaken to evaluate the role and possible interaction of the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in the acute stress-induced suppression of gonadotropin secretion in ovariectomized estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20  mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH) levels within 10  min in non-stressed animals. The naloxone-induced LH release was completely eliminated when tested 30  min after the onset of acute immobilization. In a subsequent study, it was found that suppression of the naloxone-induced LH release occurred as early as 5  min after the stress onset, and was still evident 60  min after the end of a 30-min period of immobilization. The effect of naloxone was restored 3  h after liberation of the animal from the 30-min immobilization. An intraventricular (i.c.v.) injection of CRF (1 or 5  μg) also significantly suppressed, in a dose-related manner, the effect of a subsequent i.v. injection of naloxone. However, an i.c.v. injection of α -helical CRF(9-41) (25 or 50  μg), a CRF antagonist, prior to immobilization, could not interfere with the suppressive effect of stress on naloxone-induced LH release. These results suggest that both acute immobilization stress and CRF can inhibit the LH secretory activity without mediation by EOP neurons. However, the stress-related suppression may involve non-CRF mechanism(s).     

The Japan Morning Surge-1 (JMS-1) study: protocol description.

Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (>or=135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional antihypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg/day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.     

Intravenous Gammaglobulin (IVIG): A Novel Approach to Improve Transplant Rates and Outcomes in Highly HLA-Sensitized Patients

Intravenous immunoglobulin (IVIG) products are derived from pooled human plasma and have been used for the treatment of primary immunodeficiency disorders for more than 24 years. Shortly after their introduction, IVIG products were also found to be effective in the treatment of autoimmune and inflammatory disorders. Over the past 2 decades, the list of diseases where IVIG has a demonstrable beneficial effect has grown rapidly. These include Kawasaki disease, Guillain-Barre syndrome, myasthenia gravis, dermatomyositis and demyelinating polyneuropathy. Recently, we have described a beneficial effect on the reduction of anti-HLA antibodies with subsequent improvement in transplantation of highly HLA-sensitized patients as well as a potent anti-inflammatory effect that is beneficial in the treatment of antibody-mediated rejection (AMR). These advancements have enabled transplantation of patients previously considered untransplantable. These studies and relevant mechanism(s) of action will be discussed here.     

Gastric leiomyoblastoma: report of a case

The case of a 38-year-old man with an exogastric leiomyoblastoma is reported. CT and ultrasound examinations revealed a large mass in the left hypochondrium that had both solid and cystic components. These findings mimicked those of cystadenoma of the pancreas. Because of intraperitoneal hemorrhage in the preoperative course, emergency laparotomy was performed. A large tumor was found to arise from the greater curvature of the stomach. The diagnosis was confirmed histologically.     

BUN/Cr ratio as an index of gastrointestinal bleeding mass in children.

Determining the site and severity of blood loss is important in the management of children with gastrointestinal (GI) bleeding. Blood urea nitrogen (BUN) and serum creatinine (Cr) were measured on the day of hospitalization and the ratio of BUN/Cr was calculated in 11 children with 16 episodes of upper GI bleeding and 49 with lower GI bleeding. There was a significant difference between the two GI bleeding groups with regard to BUN/Cr ratio (p less than 0.001). When the ratio was 30 or above, the specificity of upper GI bleeding was 98% with a sensitivity of 68.8%. A linear relationship was found between the BUN/Cr ratio and delta Hb (delta Hb = 0.08 x BUN/Cr +/- 0.8 g/dl) for bleeding originating from the upper GI tract. This study confirms that measurement of the BUN/Cr ratio is useful for localizing the source of bleeding to the upper GI tract and also demonstrates its usefulness as an estimation of the severity of blood loss from the upper GI tract.     

Operational lumped constant for FDG in normal adult male rats.

We determined an operational value for the lumped constant to be used in measurements of the local rate of cerebral glucose use (lCMR(glc)) with FDG in normal adult male rats. METHODS: The standard quantitative autoradiographic method was used with 2-deoxy-d-(14)C-glucose ((14)C-DG) and with (14)C-FDG in awake normal adult male rats. Timed arterial blood samples were drawn for 45 min after the bolus and assayed for plasma glucose and (14)C concentrations. At the end of the 45-min experimental period, the rats were killed, and their brains were removed and divided in half sagittally. One hemisphere was immediately frozen and assayed for local (14)C concentrations by quantitative autoradiography; the other was weighed, homogenized in t-octylphenoxypolyethoxyethanol solution, and assayed for (14)C concentrations in the whole brain by liquid scintillation counting. Paired rats (3 pairs), one in each pair receiving (14)C-DG and the other receiving (14)C-FDG, were studied in parallel on the same day. Additional unpaired animals (n = 8) were studied with either (14)C-DG or (14)C-FDG but not in parallel on the same day. To calculate the lCMR(glc) in rats studied with (14)C-FDG, the rate constants for (14)C-FDG were estimated from the (14)C-DG values determined for rats and the (14)C-FDG/(14)C-DG ratios determined for humans. In all of the rats studied with either (14)C-DG or (14)C-FDG, the lCMR(glc) was first calculated in 12 representative brain structures with the lumped constant of 0.48 previously determined for (14)C-DG in rats. The ratio of the lCMR(glc) thus determined with (14)C-FDG to that determined with (14)C-DG for each structure was then multiplied by the lumped constant for (14)C-DG to estimate the lumped constant for (14)C-FDG. The lCMR(glc) and the lumped constant for FDG in the brain as a whole were similarly estimated from the tracer concentrations in the brain homogenates. RESULTS: The mean values for the lumped constant for FDG were found to be 0.71 and 0.70 in the autoradiographic assays and the assays with brain homogenates, respectively. CONCLUSION: The appropriate value for the lumped constant to be used in determinations of the lCMR(glc) in normal adult male rat studies with (18)F-FDG and small-animal PET scanners is 0.71.