Acquired idiopathic generalized anhidrosis: a distinctive clinical syndrome

Summary The present study concerns a 28-year-old Japanese man with acquired generalized anhidrosis. The patient's ability to perspire was investigated in an artificial climate room maintained at 40°C and 40% humidity. Although the body temperature rose to 38°C, the patient did not sweat. Neither did sweating occur when the patient was given an intradermal injection of pilocarpine or nicotine. The serum IgE level was elevated. Atrophy and degeneration of the sweat glands, as well as infiltration by lymphocytes and mast cells around the sweat glands, were observed in skin biopsies. Anhidrosis in this patient was suggested to be the result of reduced function of the sweat glands themselves with possible underlying immunemediated basis.     

A novel antipsychotic, perospirone, has antiserotonergic and antidopaminergic effects in human brain: findings from neuroendocrine challenge tests

Rationale Perospirone is a new antipsychotic drug in which dopamine D₂ antagonist and serotonin 5-HT₂ antagonist effects have been found in animal studies. It was developed by a Japanese pharmaceutical company and launched in 2001. Perospirones receptor binding profile may resemble that of atypical antipsychotic drugs, but to date there has been no evidence relating to its receptor binding affinity in the human brain.Objective The purpose of this study was to investigate the receptor binding profile of perospirone via neuroendocrine challenge tests.Methods Twenty subjects (ten females and ten males) were tested on four occasions in a double-blind, cross-over design receiving: (a) placebo, (b) perospirone 4 mg, (c) paroxetine 20 mg, and (d) paroxetine 20 mg plus perospirone 4 mg, administered orally at 8.00 a.m. Plasma cortisol and prolactin levels were measured prior to administration and every hour for 6 h thereafter. In addition, psychological responses rated by visual analog scales and vital signs such as body temperature, pulse, and blood pressure were assessed in combination with blood sampling.Results Perospirone 4 mg increased prolactin levels significantly higher than placebo, whereas paroxetine 20 mg plus perospirone 4 mg significantly attenuated cortisol responses induced by paroxetine 20 mg.Conclusions The present findings suggest that perospirone has the characteristics of both D₂ and 5-HT₂ antagonist in the human brain. Further PET studies in the human brain are required in order to directly investigate these effects.     

Modification of the leukapheresis procedure for use in rhesus monkeys (Macaca mulata)

One of the most serious problems in applying leukapheresis to human infants is the large extracorporeal blood volume (ECV), resulting in substantial loss of platelets and red blood cells (RBCs). In this study, we developed a safe and effective modified procedure to collect peripheral blood stem cells (PBSCs) from rhesus monkeys (Macaca mulata) using a Baxter CS3000+ Blood Cell Separator (Baxter, Deerfield, IL) with several devices that reduced chamber size and shortened the standard apheresis kit to decrease ECV from 130 to 70 ml. Pump speed was controlled by monitoring hematocrit values and platelet counts during leukapheresis. This system makes it possible to perform safe and effective leukapheresis in rhesus monkeys whose body weight is similar to that of human infants. A total of 12 leukapheresis procedures were performed in nine monkeys and resulted in the collection of sufficient numbers of white blood cells (mean, 1.38 x 10(9) cells/kg), CD34(+) cells (mean, 17.80 x 10(6) cells/kg), mononuclear cells (mean, 3.67 x 10(8) cells/kg), and colony forming units (mean, 75.02 x 10(6) cells/kg) in all cases. In addition, no complications, such as anemia or thrombocytopenia, occurred after leukapheresis. This modified leukapheresis procedure will be useful to test new approaches in gene therapy, perform organ transplantation using nonhuman primates, and collect PBSCs from human infants in a noninvasive manner. Our nonhuman primate model provides an important framework for such future clinical studies.     

Quantitative analysis of the relationship between sedation and resting energy expenditure in postoperative patients

OBJECTIVE: To analyze quantitatively the relationship between sedation and resting energy expenditure or oxygen consumption in postoperative patients. DESIGN: A prospective, clinical study. SETTING: An eight-bed intensive care unit at a university hospital. PATIENTS: Thirty-two postoperative patients undergoing either esophagectomy or surgery of malignant tumors of the head and neck who required mechanical ventilation and sedation for > or = 2 days postoperatively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 133 metabolic measurements were performed. Ramsay sedation scale (RSS), body temperature, and the dose of midazolam were evaluated at the time of the metabolic cart study. All patients received analgesia with buprenorphine at a fixed dose of 0.625 microg x kg(-1) x hr(-1) continuously. Midazolam was used for induction and maintenance of intravenous sedation after admission to the intensive care unit. The initial dose was 0.04 mg x kg(-1) x hr(-1) and was adjusted to achieve a desired depth of sedation at 3, 4, or 5 on the RSS every 4 hrs. The degree of sedation was classified into three states: light sedation (RSS 2-3; n = 49), moderate sedation (RSS 4; n = 39), and heavy sedation (RSS 5-6; n = 45). RESULTS: With increasing the depth of sedation, oxygen consumption index (mL x min(-1) x m(-2)), resting energy expenditure index (REEI; kcal x day(-1) x m(-2)), and REE/basal energy expenditure (BEE) decreased significantly. Oxygen consumption index (mean +/- SD), REEI, and REE/BEE were 151 +/- 18, 1032 +/- 120, and 1.29 +/- 0.17 in the light sedation, 139 +/- 22, 947 +/- 143, and 1.20 +/- 0.16 in the moderate sedation, and 125 +/- 16, 865 +/- 105, and 1.13 +/- 0.12 in the heavy sedation, respectively. CONCLUSION: An increase in the depth of sedation progressively decreases in oxygen consumption index and REEI in postoperative patients.     

Behavioral recovery in a primate model of Parkinson's disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes

One potential strategy for gene therapy of Parkinson's disease (PD) is the local production of dopamine (DA) in the striatum induced by restoring DA-synthesizing enzymes. In addition to tyrosine hydroxylase (TH) and aromatic-L-amino-acid decarboxylase (AADC), GTP cyclohydrolase I (GCH) is necessary for efficient DA production. Using adeno-associated virus (AAV) vectors, we previously demonstrated that expression of these three enzymes in the striatum resulted in long-term behavioral recovery in rat models of PD. We here extend the preclinical exploration to primate models of PD. Mixtures of three separate AAV vectors expressing TH, AADC, and GCH, respectively, were stereotaxically injected into the unilateral putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys. Coexpression of the enzymes in the unilateral putamen resulted in remarkable improvement in manual dexterity on the contralateral to the AAV-TH/-AADC/-GCH-injected side. Behavioral recovery persisted during the observation period (four monkeys: 48 days, 65 days, 50 days, and >10 months, each). TH-immunoreactive (TH-IR), AADC-IR, and GCH-IR cells were present in a large region of the putamen. Microdialysis demonstrated that concentrations of DA in the AAV-TH/-AADC/-GCH-injected putamen were increased compared with the control side. Our results show that AAV vectors efficiently introduce DA-synthesizing enzyme genes into the striatum of primates with restoration of motor functions. This triple transduction method may offer a potential therapeutic strategy for PD.     

Inhibitory Effects of Conjugated Epicatechin Metabolites on Peroxynitrite-mediated Nitrotyrosine Formation

Previously, we identified four metabolites of (−)-epicatechin in blood and urine: (−)-epicatechin-3''-O-glucuronide (E3''G), 4''-O-methyl-(−)-epicatechin-3''-O-glucuronide (4''ME3''G), (−)-epicatechin-7-O-glucuronide (E7G), and 3''-O-methyl-(−)-epicatechin-7-O-glucuronide (3''ME7G) (Natsume et al. Free Radical Biol. Med. 34, 840-849, 2003). The aim of the current study was to compare the antioxidative activities of these metabolites with that of their parent compound. After oral administration of (−)-epicatechin, E3''G and 4''ME3''G were isolated from human urine, and E7G and 3''ME7G isolated from rat urine. We found that these compounds inhibited peroxynitrite-mediated tyrosine nitration, in the following order of potency: E3''G > (−)-epicatechin > E7G = 3''ME7G. = 4''ME3''G. These results demonstrate that the metabolites of (−)-epicatechin retain antioxidative activity on peroxynitrite-induced oxidative damages to some extent.     

Diagnosis and severity assessment of patients with depression

Clinically, depressive patients are increasing. It is very important but difficult to differentiate pathological depressive state from normal depressive reaction. In order to diagnose pathological depressive state (i.e. depression) and assess the severity, several diagnostic criteria and assessment scales for depression are available though most of them are provisional with limitations. In this review, Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision(DSM-IV-TR), Hamilton Rating Scale for Depression (HAM-D), and Montgomery-Asberg Depression Rating Scale (MADRS) are introduced and discussed. DSM-IV-TR is used for diagnosis and severity assessment of depression whereas HAM-D and MADRS can be used for only severity assessment.     

Single nucleotide polymorphisms of the DGKB and VCAM1 genes are associated with granulocyte colony stimulating factor-mediated peripheral blood stem cell mobilization

We previously reported the association between LDL cholesterol level (LDL-C) and granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood (PB) hematopoietic stem cells (HSC). In this study, we investigated the association between gene single nucleotide polymorphisms (SNPs) involved in hematopoiesis and lipid level and PBHSC mobilization. In 46 patients who underwent peripheral blood stem cell harvest (PBSCH), we measured CD34-positive cells in PB and PBSCH, and the patients were classified into good, intermediate, or poor mobilizer groups based on the CD34-positive cell counts. And SNPs of the OR4C12, ENO1, RERE, DGKB, DSC3, VCAM1, CD44, and FADS1 genes were investigated. The frequency of the TT type of the DGKB gene was higher in the poor mobilizer group compared to other groups (p < 0.05), whereas that of the CC type of the VCAM1 gene was high in the good mobilizer group (p < 0.05). Association with the efficiency of HSC mobilization to PB were found in the SNPs of the DGKB gene involved in cell transport and SDF-1-induced migration ability and of the VCAM1 gene which is essential for HSC homing, suggesting that SNPs involved in cell migration ability might be partly involved in HSC mobilization to PB.