Metabolism of tetrahydrobiopterin: Its relevance in monoaminergic neurons and neurological disorders

(6R)‐L‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4) is an essential cofactor for aromatic amino acid hydroxylases, such as phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), tryptophan hydroxylase, and nitric oxide synthase, which catalyze physiologically important reactions in mammals. The biosynthesis and metabolism of BH4 is usually studied mostly in the liver and only slightly in the brain, as the BH4 level in the liver is relatively high because BH4 is required for the reaction of PAH. We found that GTP (guanosine triphosphate) cyclohydrolase I, an enzyme for the biosynthesis of BH4, is a causative gene for DOPA (3,4‐dihydroxyphenylalanine)‐responsive dystonia (also called Segawa's disease), and that partial deficiency of BH4 leads to the dysfunction of the nigrostriatal dopaminergic neurons without hyperphenylalaninemia. We analyzed BH4‐deficient mice that were produced by disruption of a BH4‐synthesizing gene by a gene‐knockout technique. We found that the protein amount of TH was highly dependent on the amount of BH4, especially in nerve terminals. Our research suggests that BH4 metabolism in the brain should be different from that in the liver, and that altered metabolism of BH4 should lead to neuropsychiatric disorders including Parkinson's disease. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 378–385; 2008: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20166     

Commutativity for a Certain Class of Rings

We first establish the commutativity for the semiprime ring satisfying [x ⁿ , y]x ^r = ±y ^s[x, y ^m]y ^t for all x, y in R, where m, n, r, s, and t are fixed non-negative integers, and further, we investigate the commutativity of rings with unity under some additional hypotheses. Moreover, it is also shown that the above result is true for s-unital rings. Also, we provide some counterexamples which show that the hypotheses of our theorems are not altogether superfluous. The results of this paper generalize some of the well-known commutativity theorems for rings which are right s-unital.     

Gastroesophageal reflux laryngitis resistant to omeprazole therapy

Gastroesophageal reflux disease (GERD) is known to cause a variety of symptoms that lead a patient to seek otolaryngologic care. New advances in the treatment of GERD have enabled otolaryngologists to eliminate most of the signs and symptoms caused by acid reflux. Omeprazole, the most recent pharmacologic advancement, has been reported to be universally successful in controlling acid release from the stomach of patients with GERD. This report describes a series of patients with GERD for whom high-dose omeprazole therapy was not successful in completely reducing gastric acid levels of GERD symptomatology.     

Metal-binding properties of the peptide APP170-188: a model of the ZnII-binding site of amyloid precursor protein (APP)

Amyloid precursor protein (APP) plays a key role in Alzheimer's disease (AD), although the function of this membrane protein is still unclear. Metal ions are implicated in AD and they also interact with APP. APP possesses a strong ZnII binding site, which is evolutionary conserved. In this paper a synthetic peptide, APP170-188, with a sequence corresponding to the conserved ZnII-binding domain of APP, was synthesised and its metal-binding properties analysed. Titration experiments pointed to the binding of a stoichiometric amount of divalent ions. Further studies indicated that the binding of divalent metals like ZnII, CdII and CoII induces the dimerisation of the peptide. This dimer contains a dinuclear cluster in which the two divalent metals are bridged by two thiolate ligands from cysteine residues. The other two ligands of the tetrahedral coordination sites of each metal ion are terminal thiolate ligands. This structure was supported by the following arguments. The complex formed with CoII presents the characteristic features for tetrahedral tetrathiolate coordination in its UV-visible spectrum. The sequence of APP170-188 contains only three cysteine residues, which is incompatible with a monomeric CoII-APP170-188 complex. EPR measurements of the complex with one equivalent of CoII show almost no signal at 4 K, which is compatible with an antiferromagnetic spin-coupling of the metal ions in a cluster structure. Size-exclusion chromatography indicated that the elution time for the complexes with ZnII and CdII corresponds to the expected molecular weight of a dimer. The circular dichroism (CD) spectrum of the complex with one equivalent of CdII shows a band at 265 nm+, and an ellipticity similar to those observed for similar CdII-thiolate clusters. Possible biological implications of the ZnII binding site and the metal-induced dimerisation are discussed.     

Incidental abdominal aortic aneurysm on lumbosacral magneticresonance imaging — a case series

Magnetic resonance imaging (MRI) is commonly used as part of the assessment of patients presenting with leg/back pain to the orthopedic spinal outpatient clinic. Abdominal aortic aneurysm (AAA) can cause symptoms often similar to those of spinal stenosis. We report a case series of four patients who had incidental AAA detected on lumbosacral MRI. All patients were suffering from degenerative spinal disease and had been referred to the orthopedic spinal clinic. After history, examination and review of the imaging, all patients were referred to a vascular surgeon, and three were found to be completely asymptomatic from their aneurysm. One patient required open repair with an aortic graft due to the size of the aneurysm, although his symptoms were attributable to his spinal disease. All patients still required management of their degenerative spinal disease after their vascular review. We can find no other case reports of AAA as an incidental finding on lumbosacral MRI. This case series highlights the importance of looking at all aspects of our imaging and remembering the nonspinal causes of back and leg pains. Furthermore, in the presence of AAA when managing patients in the orthopedic outpatient setting, the authors recommend vascular review before offering orthopedic interventional management options to these patients.     

用近红外无损肌氧及运动心率检测技术评定100m极量强度运动对心脏冲击影响

利用连续双波长近红外光技术测量肌肉中血红蛋白含氧量的变化情况,同时应用运动心率无线实时采集设备,设计了检测实时肌肉组织血氧含量和瞬时心率实验方案,对6名健康男性进行了100 m跑同步实测实验。实验表明,肌肉组织氧合血红蛋白浓度在100 m跑结束后继续降低,达到最低值的时刻滞后于运动结束时刻的时间为(6.65±1.10)s;心率则在运动结束后继续上升,达到最高值的时刻滞后于运动结束时刻的时间为(8.00±1.57)s。这些结果显示了双波长近红外光组织氧测试技术和运动心率无线实时采集系统能够正确检测极量强度运动时的血氧参数和心率,揭示了极量强度运动过程中肌肉中氧运输与消耗的过程及其与心率之间的动力学特征。     

Cutaneous leishmaniasis in Peru using a vector‐host model: Backward bifurcation and sensitivity analysis

The final goal of control policies in neglected vector‐borne diseases in developing countries is to protect humans. These vector‐borne diseases include leishmaniasis, dengue, chagas, and malaria. The traditional control measures for vector‐borne diseases, as with any other illnesses, suggest to reduce the basic reproduction number below the value 1. This strategy is not necessarily sufficient when a backward bifurcation occurs. Because of its worldwide relevance, we are interested in modeling cutaneous leishmaniasis with Peru as a specific example. We use a vector‐host model with an extrinsic incubation period, which gives evidence that a backward bifurcation can occur under certain conditions. We estimate some parameters for the cutaneous leishmaniasis model in Peru. The uncertainty of the parameters suggests that we cannot guarantee the avoidance of a backward bifurcation range. It is important to be attentive to the appearance of phenomena that could make eradication more difficult. Local and global sensitivity analyses agree that is most sensitive to the number of bites by a female sandfly and its natural mortality rate. The former dependency suggests very practical control policies.     

Spatial‐temporal basic reproduction number and dynamics for a dengue disease diffusion model

A reaction‐diffusion system with free boundary is proposed to describe the transmission of the dengue disease from mosquitoes to humans. In addition to the classical basic reproduction number R₀, the spatial‐temporal basic reproduction number is introduced to determine the persistence and eradication of the disease. Some sufficient conditions for the disease vanishing or spreading are obtained. The disease will go extinct under one of the conditions: the classical basic reproduction number R₀ < 1 and the spatial‐temporal basic reproduction number with small expanding capability. The spread of the disease in the whole area is possible if for some t≥0. Numerical simulations are also given to illustrate the theoretical results.