The emerging role of Rab GTPases in the pathogenesis of Parkinson's disease

The identification of pathogenic mutations in Ras analog in brain 39B (RAB39B) and Ras analog in brain 32 (RAB32) that cause Parkinson's disease (PD) has highlighted the emerging role of protein trafficking in disease pathogenesis. Ras analog in brain (Rab) Guanosine triphosphatase (GTPase) function as master regulators of membrane trafficking, including vesicle formation, movement along cytoskeletal networks, and membrane fusion. Recent studies have linked Rab GTPases with α‐synuclein, Leucine‐rich repeat kinase 2, and Vacuolar protein sorting 35, 3 key proteins in PD pathogenesis. In this review, we discuss the various RAB GTPases associated with PD, current progress in the research, and potential future directions. Investigations into the function of RAB GTPases will likely provide significant insight into the etiology of PD and identify novel therapeutic targets for a currently incurable disease. © 2018 International Parkinson and Movement Disorder Society     

Sedation for Endoscopy

Abstract  In order to examine the investigators' clinical suspicion that Vietnamese patients were more sensitive to the sedative effects of midazolam than were Caucasians, the pharmacokinetics of a single, weight-adjusted intravenous dose of midazolam (0.05 mg/kg) were compared in a group of healthy Caucasian and Vietnamese male volunteers. The Vietnamese group ( n =8) had a significantly lower height, lean body mass and mean weight (59.8±5.5 vs 72.1±8.1 kg, respectively) compared with the Caucasian group ( n =8). No significant differences were found between the Vietnamese and Caucasian groups with regard to distribution half-life of midazolam (8.38±13.1 vs 1.49±0.63 min, respectively), elimination half-life (2.49±1.80 vs 1.48±0.66 h, respectively), clearance (4.93±1.31 vs 5.90±2.12 mL/min per kg, respectively), steady state volume of distribution (0.863±0.497 vs 0.530±0.132 L/kg, respectively) or percentage of unbound drug in plasma (4.89±0.74 vs 4.11±1.08, respectively). This suggests that dosage of midazolam in Vietnamese should be based on total body-weight. Two Vietnamese subjects who were brothers had marked elevation of distribution half-life and initial volume of distribution and lesser elevations in elimination half-life and volume of distribution at steady state. This suggests that the known subgroup of subjects who demonstrate dyshomogeneity in midazolam volume of distribution may be genetically determined.     

Vesiculation of sickle erythrocytes during thermal stress

Since it is not known why sickle RBCs tend to undergo microvesiculation, we have investigated their susceptibility to thermal stress. While normal RBCs start to vesiculate at 49.0 +/- 0 degrees C (n = 14), sickle RBCs begin to vesiculate at 47.9 +/- 0.5 degrees C, with a range of 46.5 to 48.5 degrees C (n = 14). This abnormality is reproduced by treating normal RBCs with phenazine methosulfate (PMS), which stimulates the excess intracellular generation of superoxide characteristic of sickle RBCs. For PMS-treated RBCs, there is a strong correlation between membrane protein thiol oxidation and vesiculation temperature (r = .977, P less than .001). The abnormal vesiculation temperature of both unmanipulated sickle RBCs and PMS-treated RBCs is significantly improved by treatment of the RBCs with dithiothreitol. The most dense sickle RBCs are most prone to vesiculation during thermal stress, and they are the subpopulation having the greatest amount of thiol oxidation. We conclude that the tendency of sickle RBCs to vesiculate during thermal stress is further evidence for functional abnormality of the RBC cytoskeleton due to thiol oxidation.     

Cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is a neoplasm of helper T cells whose first manifestations usually appear in the skin. The various forms of CTCL are distinguished by both clinical features and histopathology. Early on, the diagnosis may be difficult to establish because of its numerous, and often non-specific, clinical presentations. Further, the pathological findings of early lesions may lack the diagnostic features observed in well-developed or advanced disease. The diagnosis of CTCL must be considered in any patient with a chronic, therapy-resistant condition of the skin. In patients with non-specific histological findings, a high index of suspicion and multiple biopsies may eventually lead to a diagnosis of CTCL. Once the diagnosis of CTCL is established, accurate staging is essential both for its effect on treatment decisions and for its prognostic value. In general, CTCL is a chronic, slowly progressive disease with a long evolution. The development of tumours is a poor prognostic sign, as is erythroderma. The Sezary syndrome is a distinct form of erythrodermic CTCL that is characterized by exfoliative erythroderma, lymphadenopathy, lymphocytosis, intense pruritus, and circulating large, abnormal lymphocytes (Sezary cells). When death does occur, it is most often due to septicemia. Treatment of CTCL must be tailored to the individual patient. The most commonly employed treatment options are photochemotherapy and topical chemotherapy.     

4－甲基－5－取代苯氧基－伯氨喹类似物的合成及抗疟活性的初步评价

以2-硝基-4-甲氧基-5-溴乙酰苯胺为原料，经6步反应，合成了7个4-甲基-5-取代苯氧基伯氨喹类似物(Ⅱ_2～8)。抗疟活性的初步评价结果表明，这类化合物对鼠疟 Plasmodium yoelii 的病因性预防作用明显优于伯氨喹．可达伯氨唪的4～8倍；同时，Ⅱ_2～8还有较强的杀血液裂殖体作用．Ⅱ_2,5,6,8在0.781 mg·kg^-1 的剂量对原虫的抑制率为100％。     

Health promotion in hospitals: the attitudes, beliefs and practices of hospital nurses

This research paper explores the attitudes, beliefs and health promotion practices of hospital nurses working on acute adult wards, as demonstrated through the use of semi-structured postal questionnaires Responses were compared with those from hospital-based occupational therapists, physiotherapists, dietitians and medical consultants, in order to examine issues of consistency and continuity between professional groups and their interaction with patients in relation to health promotion activity The nurses are considered both as a homogeneous group and also in relation to their seniority within the profession Results demonstrate the lack of a coherent health promotion strategy within acute care settings and highlight the differing educational needs of nurses according to their professional role within the hospital By addressing these issues, a strategy can be developed to enhance health promotion in hospital by building on the concerns and needs identified by the nurses themselves Research literature and analysis of this study demonstrate that whilst the current position of health promotion in hospital is generally poor, nurses are keen to integrate health promotion into their practice     

赛庚啶对离体犬心肌肌质网Ca~(2+),Mg~(2+)—ATP酶活性和~(45)Ca~(2+)摄取功能的影响

当赛庚啶浓度在8×10~(-6)mol/L～2×10~(-4)mol/L之间时,该药对正常犬心肌肌质网Ca~(2+),Mg~(2+)—ATP酶活性几乎没有影响,仅在10~(-3)mol/L时对该酶活性才有一定的抑制作用(抑制率为39.85%,P<0.01)。正常犬心肌肌质网的~(45)Ca~(2+)摄取过程有明显的时间依赖性,至第30 min,其~(45)Ca~(2+)摄取量可达312.79±22.25 nmol/mg protein.赛庚啶对心肌肌质网的~(45)Ca~(2+)摄取有一定的抑制作用,其IC_(50)为1.94×10~(-4)mol/L。     

Inadvertent tracheobronchial placement of feeding tubes

Seventeen adult patients in whom small-diameter, flexible-tipped feeding tubes had been inadvertently placed in the lung were identified during a 22-month period. In nine patients pneumothorax developed, all cases due to transpleural passage of small-diameter (2.7-mm) feeding tubes. In one of these patients, hydropneumothorax and subsequent empyema developed. Placement of larger diameter (4.3-mm) feeding tubes did not lead to pneumothorax, but pneumonitis developed in one patient after intrapulmonary instillation of antacid solution. Of the 17 patients, 15 had impaired mental status or diminished gag, cough, or swallowing reflexes; the remaining two were pharmacologically sedated during the procedure. Radiographic confirmation of feeding tube placement is essential to avoid these complications, with particular attention paid to the course of the tube.