Evaluation of drug use practices at primary healthcare centers of Kuwait

Purpose  

The aim of this study was to investigate current prescribing and dispensing practices at primary healthcare centers in Kuwait and compare them with those reported in other countries.     

Mapping the Von Hippel -- Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis

Von Hlppel—Lindau (VHL) disease is a dominantly Inheritedfamillal cancer syndrome In which affected individuals havea greatly increased predisposition to the development of haemangloblastomasof the central nervous system and retina, renal cell carcinomaand phaeochromocytoma. The VHL gene has been mapped to chromosome3p25 -p26 by genetic linkage studies and we have previouslydemonstrated that the VHL gene is tightly linked to the D3S601locus (Zmax = 18.86 at     

Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome

Tuberous sclerosis complex (TSC) and Peutz-Jeghers syndrome (PJS) are dominantly inherited benign tumor syndromes that share striking histopathological similarities. Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC. Like TSC2, LKB1 inhibits the phosphorylation of the key translational regulators S6K and 4EBP1. Furthermore, we show that LKB1 activates TSC2 through the AMP-dependent protein kinase (AMPK), indicating that LKB1 plays a role in cell growth regulation in response to cellular energy levels. Our results suggest that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC2/mTOR pathway.     

Molecular analysis of de novo germline mutations in the von Hippel-Lindau disease gene

VHL disease is a dominantly inherited familial cancer syndromewith variable expression and age-dependent penetrance. The diagnosisof isolated cases is often delayed compared with familial cases,and estimates of the new mutation rate have varied more than20-fold. To investigate the frequency and origin of de novoVHL gene mutations we have analysed: (i) families with identicalmutations to determine if there is a common haplotype, and (ii)apparent new mutation cases to determine whether the clinicaldiagnosis of such cases is reliable and to define the parentalorigin of de novo VHL gene mutations. Haplotyping of 12 VHLmutations occurring in two or more families (total 42 kindreds)revealed that for most mutations there was no evidence of afounder effect. A marked bias for a paternal origin of new mutationshas been reported in other familial cancer syndromes such asneurofibromatosis type 1 (NF1), multiple endocrine neoplasia(MEN) 2B and bilateral retinoblastoma, but it is unclear whetherthis bias results from a greater susceptibility for mutagenesisduring male gametogenesis because of the larger number of celldivisions compared with that in oogenesis, or from genomic imprintingeffects. Analysis of 13 de novo VHL mutations in which the parentof origin could be established, showed no evidence for a biasfor a paternal origin (seven paternal, six maternal), and differedsignificantly from that reported in NF1, MEN2B and bilateralretinoblastoma. This result demonstrates that an increased susceptibilityto paternal allele mutation is not a universal finding in autosomalgenetic diseases and that the origin of new mutations may beinfluenced by both genomic imprinting effects and the increasednumber of cell divisions in spermatogenesis compared with oogenesis.     

Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers

The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer’s disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood–brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer’s risk reduction.     

槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分（英文）

目的：研究槟榔子（Areca catechu）粗提取物中所含的抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分及其作用机制。方法：使用70%甲醇水溶液对槟榔子进行粗提取。使用生物发光血小板凝集仪在富血小板血浆中测定槟榔子粗提取物的抗血小板聚集作用,使用分光光度计在试管内测定槟榔子粗提取物对乙酰胆碱酯酶活性的抑制作用。检测槟榔子中的多种化合物以测定槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分。结果：槟榔子粗提取物能够抑制花生四烯酸、二磷酸腺苷、血小板活化因子、肾上腺素及钙离子载体引起的血小板聚集,尤其对二磷酸腺苷及钙离子载体引起的血小板聚集的抑制最为明显;槟榔子粗提取物能够显著抑制乙酰胆碱酯酶的活性。在所检测的槟榔子所含化合物中,只有儿茶素对肾上腺素引起的血小板聚集有显著的抑制作用,而这种抑制作用显著弱于槟榔子粗提取物,提示槟榔子中的其他成分参与了这种抑制作用;鞣酸、没食子酸、薯蓣皂苷元和异去甲槟榔次碱能够抑制乙酰胆碱酯酶的活性,其中鞣酸的抑制作用强于槟榔子粗提取物。结论：槟榔子中含有抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分,而发挥这些功效的确切成分有待进一步的研究证实。     

Oral Fine Motor Control of Teeth Treated with Endodontic Microsurgery: A Single-Blinded Case-control Study

IntroductionPeriodontal mechanoreceptors (PMRs) are refined neural receptors present in abundance at the root apex and have a pivotal role in oral fine motor control. This case-control study aimed to evaluate the oral fine motor control of teeth treated with endodontic microsurgery (EMS) in comparison with the control teeth using a standardized behavioral biting task.MethodsFourteen eligible participants performed 5 trials of an oral fine motor control task that involved holding and splitting half of a peanut positioned on a force transducer with their EMS treated tooth and its contralateral control incisor tooth (28 teeth in total). The outcome variables were the mean food holding force, intra- and intertrial variability of the holding force, food splitting force, splitting duration, and the frequency of the stepwise splitting phase. The data were analyzed with parametric and nonparametric tests.ResultsThe results showed no statistically significant differences in the holding force, inter- and intratrial variability of the holding force, splitting force, or splitting duration between the teeth treated with EMS and the control (P > .05). However, there was a significantly higher frequency of stepwise ramp increase during the splitting phase with EMS treated teeth compared with the control (48% and 37%, respectively; P < .05).ConclusionsEMS treated teeth showed similar force regulation and oral fine motor control as the contralateral control. The findings of this study suggest that EMS treatment does not perturb the sensory information of PMRs and maintains the force regulation and oral fine motor control of the teeth.