A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma

Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.     

Clinical and microbiological profile of adult inpatients with community acquired pneumonia in Ilorin,North Central,Nigeria

BackgroundThe optimal management of community acquired pneumonia (CAP) depends on the clinical and microbiological profile in the locality.ObjectivesTo determine the clinical and microbiological profile of patients admitted with CAP in Ilorin, Nigeria.MethodsOne hundred and two consenting consecutively selected patients with clinical and radiologic confirmation of CAP were recruited in 12 months. The socio-demographic, physical examination and laboratory/radiologic parameters were documented in a questionnaire. Microbiological evaluation of their sputum was done and blood samples were taken for complete blood count, culture, serum urea and serological evaluation for atypical bacteria and some viral pathogens.ResultsCAP constituted 5.9% of the total medical admissions during the one-year study period. The mean age of the patients was 49 ± 22 years with the largest frequency in those aged 65 years and above. The commonest symptoms were shortness of breath (96.1%) and cough (94.1%), with a median duration of 3 days from symptom onset to admission. Systemic hypertension was the commonest comorbid illness (25/102; 24.5%). Klebsiella pneumoniae was the predominant pathogen isolated (20/102; 28.1%). The susceptible antibiotics were Imipenem, Ceftazidime and Ceftriaxone. Intra-hospital mortality was 17.6%. CURB – 65 score of ≥ 2 and the presence of complications of CAP were the independent predictors of mortality.ConclusionCAP constitutes a significant disease burden in Ilorin, Nigeria. Typical bacteria accounted for over half of the pathogens isolated from the patients with gram negative agents predominating. This highlights a possible shift in the microbiological profile which could guide empirical treatment.     

The effects of carnitine supplementation on clinical characteristics of patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

ObjectiveThe beneficial effects of carnitine supplementation on nonalcoholic fatty liver disease are unclear. We conducted a systematic review and meta-analysis to evaluate the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance in patients with nonalcoholic fatty liver disease.MethodsA comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases were performed. Only randomized placebo-controlled human studies that examined the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance up to September 2019 were included. Fixed effects or random-effects models were applied to compute the pooled effect size. Heterogeneity assessments were performed using Cochran’s Q test and I-squared statistics. The quality of the studies was assessed using the Jaded scale.ResultsA total of 5 articles were selected, including 334 individuals (167 in control and 167 in intervention groups). The results demonstrated that carnitine supplementation significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: −0.91; 95 % CI: −1.11, −0.72; p < 0.001, I² = 0.0 %) and the levels of aspartate aminotransferase (AST) (WMD: −16.62; 95 % CI: −28.11, −5.14; IU/l; p = 0.005, I² = 93.5 %), alanine aminotransferase (ALT) (WMD: -33.39; 95 % CI: −45.13, −21.66; IU/l; p < 0.001, I² = 93.4 %), and triglycerides (TG) (WMD: −22.13; 95 % CI: −38.91, −5.34; mg/dl; p = 0.01; I² = 0.0 %). However, the results of the pooled effect size did not show any significant effect of carnitine supplementation on body mass index (BMI) (WMD: 0.07; 95 % CI: −0.15, 0.29; p = 0.55; I² = 0.0 %), body weight (WMD: −0.28; 95 % CI: −2.23, 1.68; p = 0.78; I² = 45.7 %), the levels of gamma-glutamyl transferase (γGT) (WMD: −11.31; 95 % CI: −24.35, 1.73; IU/l; p = 0.09, I² = 61.1 %), cholesterol (WMD: −13.58; 95 % CI: −46.77, 19.60; mg/dl; p = 0.42; I² = 94.9 %), high-density lipoprotein-cholesterol (HDL-C) (WMD: 1.36; 95 % CI: −0.96, 3.68; mg/dl; p = 0.25; I² = 64.7 %), and low density lipoprotein-cholesterol (LDL-C) (WMD: −14.85; 95 % CI: −45.43, 15.73; mg/dl; p = 0.34; I² = 96.4 %).ConclusionsThis analysis shows that carnitine supplementation for patients with nonalcoholic fatty liver disease demonstrates a reduction in AST, ALT, TG levels and HOMA-IR. However, no significant effect of carnitine supplementation was observed on BMI, body weight, the levels of γGT, TC, HDL-cholesterol and LDL-cholesterol.     

Arabic adaptation of the Edinburgh cognitive and behavioural Amyotrophic lateral sclerosis screen (ECAS-AR)

Current screening batteries for assessing neuropsychological function are not specific for Amyotrophic Lateral Sclerosis (ALS) and are considered as limited tools due to the physical disabilities associated with ALS. The Edinburgh Cognitive and Behavioural ALS screen (ECAS) was developed to detect the specific cognitive and behavioral changes that may occur among ALS patients. This study presents the ECAS developed for Arabic-speaking ALS patients (ECAS-AR) for use by healthcare professionals. ECAS was translated and modified to refined variety of Arabic language. Eighty-five ALS patients were included. Normative data were collected from 200 healthy controls (among them 97 were matched). Subjects were administered the ECAS-AR and two conventional cognitive screening batteries, Frontal Assessment Battery (FAB) and Mini-Mental State Examination (MMSE). ECAS-AR discriminated well between healthy controls and ALS patients. Significant differences were noted in language, executive functions, memory, and visuospatial domains between the two groups. The most prevalent deficit occurred in language and executive functions in ALS-specific functions. Whereas memory was more readily impaired in the lower and middle education groups concerning ALS non-specific functions. Verbal fluency tended to be preserved. Positive correlations were found between ECAS-AR and the standard cognitive tests supporting its full validity. The ECAS-AR version proposed will provide rapid, efficient and sensitive tools for healthcare professional to determine the cognitive-behavioural profile in Arabic-speaking ALS patients.     

Cortical circumferential profile of SPECT cerebral perfusion in Alzheimer''s disease

We developed a semiautomatic method termed “cortical circumferential profiling” for objective analysis of cerebral cortex function in emission tomographic neuroimaging studies. This method treats cortex as a continuous ring near the outer brain edge. A computer algorithm samples the cortex at 60 contiguous, equiangular locations, using 1-cm² samples. These values are plotted as a function of cortical angle to produce the cortical circumferential profile. This method was used in a study of regional cerebral perfusion in 15 patients with Alzheimer's disease and 8 elderly control subjects using N-isopropyl [I-123]-iodoamphetamine. Cortical circumferential profiling decreases variability, examines the entire cortex within slices at preselected levels above the orbital-meatal line, and facilitates intrasubject and intersubject comparisons.     

软胶囊崩解迟缓现象影响因素研究

目的：研究储存条件以及软胶囊处方对明胶胶片稳定性的影响，探讨软胶囊崩解迟缓的原因。方法：制备明胶胶片模拟软胶囊囊壳，采用溶胀动力学法测定明胶胶片平衡溶胀量(Seq)，同时测定软胶囊内容物溶媒PEG400中甲醛含量。以上述结果为指标，考察不同储存条件与胶囊处方对明胶胶片交联程度的影响。结果：空白明胶胶片在40℃条件下Seq与对照组具有极显著性差异，PEG400中甲醛含量增加。含有甘油、山梨醇、二氧化钛等辅料的胶片浸泡在PEG400中后Seq与对照组具有极显著性差异，PEG400中甲醛含量量著增加。加速条件下含有抗氧剂的胶片Seq与PEG400中甲醛含量变化不大。结论：在考察的储存条件中，温度对软胶囊稳定性影响较大。含有一些常用辅料的明胶胶片易受PEG400中外源性醛类杂质的影响，Seq降低。低沮保存、纯化辅料以及添加抗氧剂有助于缓解软胶囊崩解迟缓现象的发生。     

The effect of seamustard on blood lipid profiles and glucose level of rats fed diet with different energy composition

Recently, Korean people are consuming seaweeds almost 3.5 times more now than three decades ago. It is well known that seaweeds contain lots of soluble dietary fiber in addition to micronutrients such as β-carotene, iodine and some bioactive components. Seaweeds are considered to be effective for preventing chronic diseases including obesity, diabetes mellitus, atherosclerosis, cancer or constipation. This study was conducted to investigate the effect of seamustard intake on body weight gain, blood glucose level and lipid profiles in rats fed diets with different energy nutrient composition. Male Sprague-Dawley rats (average initial weight 103.7 g) were divided into groups for two experiments as follows; Control, M2.5 & M5 groups (Exp. I) and M5, M10, HCM5, HCM10, HFM5 & HFM10 groups (Exp. II). The rats were fed diet and water ad libitum for 4 weeks. In general, there was no significant difference in blood glucose and triglyceride concentration among groups. In Exp. I, serum LDL-cholesterol level of rats fed diet with 5% seamustard powder (M5) was significantly lower than that of control group, while HDL-cholesterol level, TC/LDL ratio and weight of adrenal gland were higher. In Exp. II, food intake, body weight gain and EER of high fat diet with 10% seamustard group (HFM10) were the lowest among groups. Except gastrocnemius muscle, all organ weights of HFM10 group were the lowest. Fecal cholesterol excretion and serum LDL-cholesterol concentration of HFM10 group were the highest, while serum HDL-cholesterol level was the lowest among groups. Interestingly, HDL-cholesterol concentration was the highest in HCM5 group among groups. From these results, it was suggested that seamustard intake might be more effective for body weight control, but not for improving blood lipid profiles in high fat diet than in high carbohydrate diet.     

Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T.

An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models.     

东北地区2000～2005年住院军事飞行人员疾病构成和常见病疾病谱调查

目的 探讨东北地区2000～2005年住院军事飞行人员疾病的发生、发展与分布规律,为完善新时期飞行人员疾病预防、诊治和医学鉴定提供客观依据. 方法 采用流行病学回顾性调查方法 ,统计分析东北地区2000～2005年2223人次住院军事飞行人员的病例资料,并按国际疾病分类法第9版(ICD-9)编制"东北地区2000～2005年军事飞行人员疾病构成"和"东北地区2000～2005年军事飞行人员常见病疾病谱".应用SPSS 10.0统计软件进行统计分析. 结果 疾病构成显示,军事飞行人员肌肉骨骼系统疾病多年居首位,构成比是居第2位的消化系统疾病的2～3倍.与1995年比较,肌肉骨骼系统、感觉器官及泌尿生殖系统疾病的构成比上升显著;疾病谱显示腰椎间盘突出症、颈椎病、头痛、神经性耳聋和心律失常居前5位. 结论 21世纪前6年东北地区军事飞行人员常见病是腰椎间盘突出症、颈椎病、头痛、神经性耳聋和心律失常.提示转氨酶增高、半月板损伤和颈椎间盘突出症增加迅速,应引起关注.