Disorders of phosphate metabolism in chronic renal disease

Hyperphosphatemia directly or indirectly contributes to the progression of chronic renal disease and is an important factor in the development of secondary hyperparathyroidism and uremic bone disease. New therapeutic advances include the development of calcium-free intestinal phosphate binders, calcimimetics to control parathyroid hormone secretion and non-calcemic vitamin D analogs.     

A novel function of tetrahydrobiopterin]

6R-L-erythro-5, 6, 7, 8-Tetrahydrobiopterin (6R-BH4) is known as a cofactor for the hydroxylases of phenylalanine, tyrosine and tryptophan and also as a cofactor for nitric oxide synthase. Recently, a novel function of 6R-BH4 has been found: that is, 6R-BH4 acts on specific membrane receptors to directly stimulate the release of monamine neurotransmitters such as dopamine and serotonin, independently of its cofactor activity. In addition, it indirectly stimulates the release of non-monoamine neurotransmitters such as acetylcholine and glutamate, through activation of monoaminergic systems. In this paper, we briefly review recent experimental data, which provide new insights into the role of 6R-BH4 as a regulator of neuronal function. We also discuss the possibility of treatment by 6R-BH4 of neuropsychiatric diseases such as Parkinson's disease, Alzheimer's disease, depression and infantile autism.     

The regulation of vascular tetrahydrobiopterin bioavailability

6R l-erythro-5,6,7,8-tetrahydrobiopterin (BH₄) is an essential cofactor for several enzymes including phenylalanine hydroxylase and the nitric oxide synthases (NOS). Oral supplementation of BH₄ has been successfully employed to treat subsets of patients with hyperphenylalaninaemia. More recently, research efforts have focussed on understanding whether BH₄ supplementation may also be efficacious in cardiovascular disorders that are underpinned by reduced nitric oxide bioavailability. Whilst numerous preclinical and clinical studies have demonstrated a positive association between enhanced BH₄ and vascular function, the efficacy of orally administered BH₄ in human cardiovascular disease remains unclear. Furthermore, interventions that limit BH₄ bioavailability may provide benefit in diseases where nitric oxide over production contributes to pathology. This review describes the pathways involved in BH₄ bio-regulation and discusses other endogenous mechanisms that could be harnessed therapeutically to manipulate vascular BH₄ levels.     

Disorders in bone metabolism of female rats chronically exposed to cadmium

The effect of cadmium (Cd) on bone metabolism during skeletal development and maturity was investigated on a rat model of human exposure. Young female Wistar rats were exposed to 1, 5, or 50 mg Cd/l in drinking water for 3, 6, 9, and 12 months. Total bone mineral density (T-BMD), bone mineral content (BMC), density (BMD), and bone area at the femur and lumbar spine (L1-L5) were measured densitometrically. Alkaline phosphatase (ALP) and osteocalcin (OC) as bone formation markers, and carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in bone (trabecular and cortical) or serum as bone resorption markers were measured. Renal calcium (Ca) handling and Cd body burden were evaluated as well. At the stage of intensive skeletal development (the first 6 months of the experiment), at all exposure levels, Cd inhibited the processes of bone formation and as a result disturbed the accumulation of bone mass leading to osteopenia (- 1 > Z score/T score BMD > -2.5) and at 5 and 50 mg Cd/l even to more advanced disorders in the BMD. Continuation of the exposure up to skeletal maturity led to high bone turnover with increased resorption enhancing the prevalence of osteopenia or the BMD values having the Z score/T score < -2.5. The results allow for the conclusion that chronic, even low-level exposure to Cd disturbs bone metabolism during skeletal development and maturity by affecting bone turnover most probably through a direct influence on bone formation and resorption, and indirectly via disorders in Ca metabolism. Our findings confirm the hypothesis that environmental exposure to Cd may be a risk factor for low BMD.     

Autophagy & Phagocytosis in Neurological Disorders and their Possible Cross-talk

Autophagy and phagocytosis are two important endogenous lysosomal dependent clearing systems in the organism. In some neurological disorders, excessive autophagy or dysfunctional phagocytosis has been shown to contribute to brain injury. Recent studies have revealed that there are underlying interactions between these two processes. However, different studies show inconsistent results for the contribution of autophagy to the phagocytic process in diverse phagocytes and relatively little is known about the link between them especially in the brain. It is critical to understand the role that autophagy plays in phagocytic process in order to promote the clearance of endogenous and exogenous detrimental materials. In this review, we highlight the studies focusing on phagocytosis and autophagy occurring in the brain and summarizing the possible regulatory roles of autophagy in the process of phagocytosis. Balancing the roles of autophagy and phagocytosis may be a promising therapeutic strategy for the treatment of some neurological diseases in the future.     

Therapeutic potential of tetrahydrobiopterin for treating vascular and cardiac disease

Tetrahydrobiopterin is the reduced unconjugated pterin that serves as an essential cofactor for the normal enzymatic function of the aromatic amino acid hydroxylases and for the nitric oxide synthases (NOS). Its role in the latter biochemistry is being increasing appreciated, as depletion or oxidation of BH4 results in a condition of NOS uncoupling, resulting in a nitroso-oxidative imbalance. Recent experimental studies support an important pathophysiologic role of BH4 deficiency as well as the therapeutic potential of BH4 repletion for hypertension, endothelial dysfunction, atherosclerosis, diabetes, cardiac hypertrophic remodeling, and heart failure. In addition to BH4, studies are also examining the potential role of folic acid therapy, because folic acid can enhance BH4 levels and the NOS coupling state. This review summarizes these recent studies focusing on the biochemistry and pharmacology of BH4 and its potential role for treating cardiovascular disease.     

齐拉西酮与氨磺必利治疗急性期精神分裂症的疗效及对糖脂代谢影响比较

目的比较抗精神病药物齐拉西酮与氨磺必利治疗急性期精神分裂症患者的疗效及对糖脂代谢的影响。方法选择2017年3月-2018年12月山东省临沂市精神卫生中心符合ICD-10诊断标准的首发或复发急性期精神分裂症患者64例,采用随机数字表法分齐拉西酮组和为氨磺必利组,每组32例,比较2组治疗前、治疗第2周末、第4周末、第6周末、第8周末PANSS量表评分及空腹血糖、血脂水平。结果治疗第2周末和第8周末齐拉西酮组阳性症状评分低于氨磺必利组(P<0.05);治疗第4周末、第6周末2组阳性症状评分比较差异无统计学意义(P>0.05)。齐拉西酮组第4、6、8周末阴性症状评分高于氨磺必利组(P<0.05或P<0.01)。2组治疗前、治疗第2、4、6、8周末精神病理评分和总分比较差异无统计学意义(P>0.05)。治疗后第8周末,齐拉西酮组FBG、TC、TG、HDL-C、LDL-C与治疗前比较差异均有统计学意义(P<0.05);氨磺必利组FBG、TC、TG、HDL-C、LDL-C与治疗前比较差异无统计学意义(P>0.05)。结论齐拉西酮与氨磺必利治疗急性期精神分裂症患者的疗效相当,氨磺必利更利于改善阴性症状,齐拉西酮控制阳性症状起效更快,齐拉西酮对血糖、血脂代谢的影响更大。     

超级细菌及其感染治疗药物

抗菌药物是治疗和控制感染性疾病的重要手段.然而,随着抗菌药物滥用现象的日益严重,各种超级细菌相继出现,人类又将再次面临"无药可医"的局面.本文介绍4种在临床上较具代表性的耐药菌株,对临床相关感染的治疗药物评价予以综述.