Islet hyperperfusion during prediabetic phase in OLETF rats,a model of type 2 diabetes

Although it has been hypothesized that initial hyperperfusion followed by late hypoperfusion in islet circulation occurs in rodent models of type 2 diabetes, islet blood flow has not been measured during prediabetic phase. We studied islet blood flow in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of slowly progressive obese type 2 diabetes. Islet blood flow was measured by the two-color microsphere method under anesthesia at different ages. Islet blood flow was significantly higher in young OLETF rats compared with control Long-Evans Tokushima Otsuka (LETO) rats when the former were not obese or diabetic and had normal insulin secretion at 5 weeks of age (LETO 4.6 +/- 1.1, OLETF 8.8 +/- 1.2 ml. min(-1). mg(- 1), P < 0.01). At 6 months of age, islet hyperperfusion was observed in OLETF rats, and >40% of whole pancreatic blood flow was diverted into islets in OLETF rats. Prevention of obesity by food restriction increased basal islet blood flow. On the other hand, long-term hyperglycemia induced by sucrose feeding decreased fractional islet blood flow as well as glucose-stimulated islet blood flow. Our results indicate that hyperperfusion is present during the preobese and prediabetic phase in our type 2 diabetes rats.     

A case of acid burn of the penis

A 27-year-old man presented to our hospital complaining of multiple mild injuries sustained in an attack of violence at the workplace. He had received chemical burns to the penis induced by hydrochloric acid and had developed severe phimosis. He complained of pain on erection and ballooning during urination. The foreskin was partially resected with foreskin grafting for the stricture. The postoperative outcome was favorable and his symptoms were relieved.     

Reconstruction of right ventricular outflow tract with stentless xenografts in Ross procedure

To investigate whether the use of a stentless porcine aortic xenograft can be an alternative for right ventricular outflow tract (RVOT) reconstruction during the Ross procedure, 9 patients underwent the Ross procedure and RVOT reconstruction with a stentless xenograft since January 2000. After the aortic valve was replaced with a pulmonary autograft, a stentless xenograft with a xeno- pericardial roll was implanted in the RVOT. One patient required subsequent aortic valve replacement because of severe regurgitation of the pulmonary autograft. All patients recovered well from the operation. The right ventricle-pulmonary arterial pressure gradient was 18 +/- 7 mm Hg at discharge and was not significantly increased during the 2-year follow-up period. Although 1 patient died of ventricular arrhythmia 5 months after, his cardiac function was normal, and transpulmonary valve pressure was 19 mm Hg in the follow-up. The other 7 patients are currently in New York Heart Association functional Class I. Although long-term follow-up is required to explain the durability, the stentless xenograft with a pericardial roll is considered to be an alternative for reconstruction of the RVOT within 2 years after the Ross procedure.     

Impact of Prol2Ala variant in the peroxisome proliferator-activated receptor (PPAR) gamma2 on obesity and insulin resistance in Japanese Type 2 diabetic and healthy subjects

The peroxisome proliferator-activated receptor (PPAR) gamma is an important regulator of adipocyte differentiation and a modulator of intracellular insulin-signaling events. We examined the roles of the Pro12Ala variant of PPAR gamma2 in obesity and insulin resistance in 402 Japanese patients with type 2 diabetes and 116 control subjects. Among the diabetes subjects, the Pro12Pro homozygotes showed significantly higher body mass index (BMI) than those with the Pro12Ala variant (p = 0.020), while there was no association between genotype and BMI in the controls. Furthermore, diabetic subjects with Pro12Pro showed significantly higher fat body mass index (FBMI) than those with Pro12Ala (p = 0.016), while no association between genotype and lean body mass index (LBMI) was observed. Regarding insulin resistance, there was no difference in the HOMA index or in clamp index between Pro12Ala and Pro12Pro variants. These data suggest that the Pro12Ala polymorphism of PPAR gamma2 does not influence insulin resistance but body composition in Japanese diabetic subjects.     

Effects of low-dose ketamine on neuropathic pain: An electroencephalogram-electrooculogram/behavioral study

The aim of the present study was to clarify the neurophysiological changes associated with analgesic and behavioral effects of low-dose ketamine HCl in patients suffering from chronic neuropathic pain. Ten in-patients with neuropathic pain participated in this single-blind, placebo-controlled study after giving written informed consent. Following intravenous injections of a saline solution (placebo), three bolus injections of 5 mg ketamine HCl were administered at 5 min intervals. Changes in pain perception were assessed using a numerical rating scale for pain. Behavioral changes, including psychotomimetic effects, were assessed using the Brief Psychiatric Rating Scale (BPRS). Electroencephalograms (EEG) and electrooculograms (EOG) were recorded continuously throughout the testing period. One minute EEG and closed-eye eye movements were quantified. The effects of ketamine were evaluated by comparing the neurophysiological and behavioral parameters obtained from the placebo and ketamine trials. Pain reduction was significantly correlated with ketamine-induced changes in hallucinatory behavior and excitement as measured by the BPRS. Ketamine injections caused a significant decrease in the EEGalpha amplitude without an accompanying reduction in EEG frequency. The EEGalpha amplitude reduction at the right central electrode was significantly related to subjective pain relief. Subanesthetic doses of ketamine significantly decreased rapid eye movements, but did not initiate slow eye movements. In conclusion, the present EEG-EOG/behavioral results indicate that ketamine-induced failure of neural integration between cortical-subcortical regions induces psychotic symptoms and alters pain perception on neuropathic pain.     

Compartments in the lamprey embryonic brain as revealed by regulatory gene expression and the distribution of reticulospinal neurons

The vertebrate neural tube consists of a series of neuromeres along its anteroposterior axis. Between amphioxus that possesses no neuromeres and gnathostomes, the lamprey occupies a critical position in the phylogeny for the origin of the segmented brain. To clarify the rhombomeric configuration of the Japanese lamprey, Lampetra japonica, we injected rhodamine- and fluorescein-labeled dextrans into the larval spinal cord, and retrogradely labeled the reticulospinal neurons. We also isolated prosomere marker genes from the embryonic cDNA library of L. japonica, and performed in situ hybridization on the embryonic brain. Of the genes examined, LjOtxA, LjPax6, LjPax2/5/8, LjDlx1/6, and LjTTF-1 were expressed in clearly demarcated polygonal domains. In the telencephalon, LjDlx1/6, LjPax6, and a putative paralogue of LjEmx were expressed in different domains; the LjEmx paralogue was expressed in the dorsal region, and LjDlx1/6 and LjPax6 in a complimentary fashion of the middle part. These expression patterns implied existence of a tripartite configuration of the lamprey telencephalon similar to that in gnathostomes. All these evidences strongly suggest that the segmental and compartmental architecture of the vertebrate brain was already established before the divergence of agnathans and gnathostomes.     

Chronic cervical and lumbar epidural catheterization through the atlanto-occipital membrane in rats

We report here an efficient means of epidural catheter placement through atlanto-occipital membrane in rats. METHODS: Male SD rats (n = 84) were divided into lumbar (n = 48) and cervical (n = 36) groups. Under sterile technique, PVC V-1 tubing was inserted and advanced caudally targeted to the C 4 or L 4 level. Analgesic efficacy and duration were measured by injecting increments of 2% lidocaine until a maximum paw withdrawal latency time from a radiant heat thermal stimulator. Rats (n = 6 each day) were sacrificed and an autopsy was performed to observe both the laterality of the catheter tip and the proliferation of fibrous tissue around the catheter. RESULTS: The volume of lidocaine and its duration was 52 +/- 17 microliters and 27 +/- 13 min (mean +/- SD) in lumbar, 30 +/- 10 microliters and 26 +/- 9 min in cervical group. In lumbar group, two catheters penetrated the dura. The remaining catheters were confirmed to be in the epidural space within L 4 +/- 1 or C 4 +/- 2 segment. Lumbar catheter tips were almost equally distributed between the center, left and right, while cervical catheter tips were distributed between left and center portion of the epidural space. The severity of tissue proliferation was time dependent. The proliferation of fibrotic tissue seemed more rapid in cervical than lumbar group. CONCLUSION: Although this approach for epidural catheter placement is efficient and produces excellent drug effects on day 3 after implantation, as reported by others, rapid development of fibrous tissue around the catheter quickly limits the usefulness of the epidural catheter.     

Retroperitoneal bronchogenic cyst: a case report

A rare case of retroperitoneal bronchogenic cyst is presented. A 50-year-old man was referred to our hospital for an investigation of a retroperitoneal mass. Computed tomography and magnetic resonance imaging confirmed a retroperitoneal mass, about 4 cm in diameter, adjacent to the left kidney and spleen. On the basis of these imaging modalities, a definitive diagnosis of this mass could not be made. So, resection of the mass was performed. The removed mass was an unilocular cyst and filled with mucinous fluid. Histopathologically, the cyst wall was composed of a fibrovascular connective tissue containing mucus-secreting glands and cartilages and was lined by ciliated pseudostratified columnar epitherium. Thus, a diagnosis of bronchogenic cyst was made. Bronchogenic cysts are rare congenital anomalies of the primitive foregut and usually develop in the mediastinum and lung.     

Synthesis,beta-adrenoceptor pharmacology and toxicology of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride,a short acting beta(1)-specific antagonist

The synthesis of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride (D140S.HCl 6), a novel short acting beta(1)-specific adrenoceptor antagonist, has been described. The antagonist potency for D140S.HCl 6 has been compared with esmolol, another short acting agent, and other well known beta-adrenoceptor antagonists in isolated rat tissue preparations. The pharmacokinetics of D140S.HCl 6 in 7 day continuous intravenous infusions and 4 weeks intravenous bolus injection studies in conscious rats and dogs have been examined in toxicology studies. The effect on the isoprenaline-induced heart rate increase and the pharmacodynamic half-life of D140S.HCl 6 has been compared with esmolol in a conscious rat model. In addition, the results of a range of toxicological studies are presented. The results indicate that D140S.HCl 6 is a highly specific beta(1)-adrenoceptor antagonist (pA(2) = 8.15+/-0.22, beta(1)/beta(2) selectivity > 4400). The in vitro studies suggest D140S.HCl is ca. ten times more potent and 60 times more beta(1)-specific than racemic esmolol. Pharmacokinetic non-linearity was seen when given as a 7 day intravenous infusion at toxicological doses above 10 mg kg(-1) h(-1) in the rat and 2.5 mg kg(-1) h(-1) in the dog. Both D140S.HCl 6 and esmolol have very short durations of action after intravenous infusion in the rat (pharmacodynamic half-life is < 15 min for D140S.HCl and 10 min for esmolol). The toxicological tests indicate that D140S.HCl 6 shows no unexpected toxicity and none of the tissue irritancy problems reported for esmolol formulations.