Association between alcohol consumption and both osteoporotic fracture and bone density

Objective

Alcoholism is a risk factor for osteoporotic fractures and low bone density, but the effects of moderate alcohol consumption on bone are unknown. We performed a systematic review and meta-analysis to assess the associations between alcohol consumption and osteoporotic fractures, bone density and bone density loss over time, bone response to estrogen replacement, and bone remodeling.

Methods

MEDLINE, Current Contents, PsychINFO, and Cochrane Libraries were searched for studies published before May 14, 2007. We assessed quality using the internal validity criteria of the US Preventive Services Task Force.

Results

We pooled effect sizes for 2 specific outcomes (hip fracture and bone density) and synthesized data qualitatively for 4 outcomes (non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling). Compared with abstainers, persons consuming from more than 0.5 to 1.0 drinks per day had lower hip fracture risk (relative risk = 0.80 [95% confidence interval, 0.71-0.91]), and persons consuming more than 2 drinks per day had higher risk (relative risk = 1.39 [95% confidence interval, 1.08-1.79]). A linear relationship existed between femoral neck bone density and alcohol consumption. Because studies often combined moderate and heavier drinkers in a single category, we could not assess relative associations between alcohol consumption and bone density in moderate compared with heavy drinkers.

Conclusion

Compared with abstainers and heavier drinkers, persons who consume 0.5 to 1.0 drink per day have a lower risk of hip fracture. Although available evidence suggests a favorable effect of alcohol consumption on bone density, a precise range of beneficial alcohol consumption cannot be determined.     

Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet’s disease: a study in Algerian patients

Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet’s disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.     

Synthesis,acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities,and molecular docking studies of a novel compound based on combination of flurbiprofen and isoniazide

Synthesis of a compound with balanced bioactivities against a specific target is always a challenging task. In this study, a novel compound (1) has been synthesized by combination of flurbiprofen and isoniazide and shows ∼2.5 times enhanced acetylcholinesterase (AChE) inhibition activity and ∼1.7 times improved butyrylcholinesterase (BuChE) inhibition activity compared to flurbiprofen and a standard drug (i.e. physostigmine). A comparative AutoDock study has been performed, based on the optimized structure, by the DFT/B3LYP method, which confirmed that compound (1) is more active against AChE and BuChE, with calculated binding energies of −12.9 kcal mol⁻¹ and −9.8 kcal mol⁻¹ respectively as compared to flurbiprofen and an eserine (physostigmine) standard for which the binding energy was calculated to be −10.1 kcal mol⁻¹ and −8.9 kcal mol⁻¹, respectively. A mixed mode of inhibition of AChE and BuChE with compound 1 was confirmed by Lineweaver–Burk plots. AChE and BuChE inhibition activity alongside docking results suggests that compound (1) could be used for treatment of Alzheimer''s disease. Moreover, compound (1) also exhibit better α-chymotrypsin activity compared to flurbiprofen. Furthermore, in vitro and in vivo analysis confirmed that compound (1) exhibit more activity and less toxicity than the parent compounds.

A novel compound (1) shows ∼2.5 and ∼1.7 times enhanced AChE inhibition activity and BuChE inhibition activity respectively compared to flurbiprofen and standard drug (i.e. physostigmine). It has also been confirmed by comparative AutoDock studies.     

Attachment and psychological well-being among adolescents with and without disabilities in Kenya: The mediating role of identity formation

The current study is aimed at evaluating the relationship between attachment and identity development, and their influence on psychological well-being in adolescents with and without disabilities in Kenya. The sample was composed of 296 adolescents (151 with disabilities and 145 without any disability). The mean age in our sample was 16.84 years (SD = 1.75). Adolescents with disabilities had significantly lower scores in identity formation, paternal attachment, and life satisfaction. A path model indicated that identity formation partially mediated the relationship between secure attachment and psychological well-being. Our findings indicate that both parent and peer attachment play an important role in the identity formation and psychological well-being of adolescents in Kenya, irrespective of a disabling condition. A multigroup analysis indicated that while the structure of the relationship between variables held for groups, the pattern and strength of the relationships differed. Implications for practice, especially the guidance and counseling services in schools, are discussed.     

Use of Cyclodextrin as a Novel Agent in the SEC-HPLC Mobile Phase to Mitigate the Interactions of Proteins or Peptide or their Impurities with the Residual Silanols of Commercial SEC-HPLC Columns with Improved Separation and Resolution

Purpose

Accurate quantification of the intact proteins, antibodies or peptides and their impurities without interaction to silanols of HPLC column.

Methods

Hydroxypropyl ß Cyclodextrin (HPCD) is added in the mobile phase at different concentrations. Different commercial SEC-HPLC columns and biologics with a molecular weight ranging from 5.8 kDa to 150kDa were assessed with and without cyclodextrin.

Results

Addition of non-ionic sugars such as Hydroxypropyl ß Cyclodextrin in the mobile phase, resulted improved peak performance such as theoretical plates, peak resolution, peak width, peak height, and improved quantification of aggregates in biologics such as antibodies Humira and Actemra, and peptides such as insulin. There is an increase in peak height, reduced retention time, increased plate and reduced peak width with increasing concentration of cyclodextrin studied.

Discussion

High ionic strength, basic amino acids such as arginine, organic solvents (with a concentration low enough not to precipitate protein), sodium perchlorate and ion pairing agents in the mobile phase used for separation of peptides, proteins and antibodies to prevent silanol interaction. These commonly used solutions are not always successful, as they not only interact with the biologic, but are sometimes, not compatible. The non-ionic cyclodextrin itself does not cause protein aggregation but prevents the nonspecific binding or interaction of protein itself and thereby allowing for improved resolution, and accurate quantification of aggregates in antibodies, and peptides. The data on the separation in presence of cyclodextrin in the mobile phase showed higher peak resolution, improved peak shape, accurate apparent molecular weight, improved efficiency, and less peak tailing for biological products.

Conclusion

Hydroxypropyl ß Cyclodextrin in the mobile phase, resulted improved SEC-HPLC resolution, and quantitation of aggregates in biologics by preventing the interaction of biologics to silanol of the commercial SEC-HPLC columns.

     

Physical exercise is associated with better fat mass distribution and lower insulin resistance in spinal cord injured individuals

Objectives

The aim of the study was to compare total and regional body composition and their relationship with glucose homeostasis in physically active and non-active individuals with cervical spinal cord injury (c-SCI).

Methods

Individuals with lesion level between C5–C7 were divided into two groups: physically active (PA; n = 14; who practiced physical exercise for at least 3 months, three times per week or more, minimum of 150 minutes/week): and non-physically active (N-PA n = 8). Total fat mass (t-FM) and regional fat mass (r-FM) were assessed by dual energy X-ray absorptiometry. Fasting plasma insulin (FPI) was determined by enzyme-linked immunosorbent assay.

Results

PA group present lower (P < 0.01) total fat mass (t-FM), % and kg, regional fat mass (r-FM), % and kg, FPI levels and HOMA index, while they had higher (P < 0.001) total free fat mass (t-FFM), %, and regional free fat mass (r-FFM), %, compared to the N-PA group. In the N-PA group, FPI and HOMA index were negatively (P < 0.05) correlated with FFM% (r = −0.71, −0.69, respectively) and positively correlated to trunk-FM (r = 0.71, 0.69, respectively) and trunk-FM:t-FM (kg) ratio (r = 0.83, 0.79, respectively).

Conclusion

Physical exercise is associated with lower t-FM, r-FM, and insulin resistance, which could contribute to the decrease of the risk of cardiovascular and metabolic conditions in individuals with c-SCI.