Current clinical pharmacology最新文献

Background: Diabetic Nephropathy is a frequent complication of diabetes mellitus due to functional and structural modifications in multiple kidney compartments. Probiotics have risen lately as a forthcoming therapeutic intervention but they have not been systematically evaluated in diabetic nephropathy so far. The aim of this systematic review was to evaluate randomized controlled trials and experimental studies assessing the effect of probiotic supplements on diabetic nephropathy.

Methods: An extensive literature search was conducted through electronic databases (PubMed, Scopus, Cinahl and Medline) with the Medical Subject Headings and entry terms of "diabetic nephropathy", "diabetic renal disease" and "probiotics". The search yielded 116 results, 9 of which met the inclusion criteria for this systematic review.

Results: Most of the microorganisms used in the studies belonged to the Lactobacillus and Bifidobacterium genus. The dosage ranged from 2×107 to 6×1010 CFU/ g. The form of the probiotics varied across the studies (capsules, sachets, soy milk, kefir and honey). The majority of the studies demonstrated the benefits of probiotic supplementation on the reduction of inflammation, oxidative stress and on the amelioration of renal function biomarkers in subjects with diabetic nephropathy. No major gastrointestinal adverse events were observed during the intervention time with probiotics.

Conclusion: Findings of this systematic review demonstrate the positive impact of probiotics on Diabetic Nephropathy without any major adverse events. Moreover, future larger randomized controlled trials with bigger samples and longer follow-up time are deemed necessary for further valid results on the effectiveness of probiotic supplementation on Diabetic Nephropathy.

Inflammatory bowel diseases, namely Crohn's disease and ulcerative colitis, are currently considered multifactorial pathologies in which various combined environmental factors act on genetic background, giving rise to chronic inflammation of the gastrointestinal tract. Ulcerative colitis is an inflammation of the colon caused by a dysregulated immune response to host intestinal microbiota in genetically susceptible subjects. Ulcerative colitis has a strong impact on patients' quality of life, as well as high costs for the health-care system. A great interest on the role of intestinal microbiota modulation in ulcerative colitis is emerging. Several studies have shown an improvement of inflammatory markers and symptoms in ulcerative colitis patients through treatments with probiotics and prebiotics separately. Despite the low number of studies on the treatment of ulcerative colitis by specific strains of probiotics plus selected prebiotics, i.e. synbiotics, the results are promising, even if discordant. The mechanism of action in synbiotics supplementation is still unclear and needs more investigation, although there is a large number of data indicating that the synergism between probiotics and prebiotics favours the survival and implantation of probiotics into the gastrointestinal tract with beneficial effects on human health by modulating the inflammatory response and gut microbiota composition. The aim of this minireview is to describe the main in vitro, animal and human studies performed up to now, that have used synbiotics to treat ulcerative colitis, and to highlight limitations and future perspectives.

Background: Poor adherence to the prescribed therapy leads to low bone mineral density and enhance the development of osteoporosis complications and unnecessary hospitalization.

Objective: To explore factors associated with medication non-adherence in patients with osteoporosis. Findings would help guide the development of future pharmaceutical care interventions aim at improving health outcomes for patients with osteoporosis.

Methods: The study was conducted at an outpatient osteoporosis clinic at the Royal Medical Services Hospital. Variables including socio-demographics and medical factors were collected using medical records and custom-designed questionnaire. Medication adherence was assessed using the validated 4-item Morisky Medication Adherence Scale. Logistic regression was performed to develop a model with variables that best predicted medication non-adherence in patients with osteoporosis in Jordan.

Results: A total of 296 patients participated in the study. Most of the study participants (72.3%) were found non-adherent. Patients were found less likely to adhere to the prescribed medications with each unit increase in the number of prescribed medications (OR = 2.503, CI = 1.103-5.680) and if they did not have a trust in the efficacy of the medications (OR = 5.544, CI = 0.990-31.058).

Conclusion: Medication adherence for patients with osteoporosis has considered scope for improvement in Jordan. Simplifying dosage regimen in addition to taking patients' preferences when selecting the medications should be taken into account in future interventions designed to improve health outcomes for patients with osteoporosis.

Constipation is a highly prevalent functional gastrointestinal disorder that may significantly affect the quality of life and health care costs. Treatment for constipation has been broadly reviewed by cognitive therapies, medications, and surgical interventions. Gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli have been demonstrated in functional gastrointestinal disorders and prebiotics to play a role in augmenting their presence. Prebiotics are ingredients in foods that remain undigested, stimulating the bacteria. There are a variety of prebiotics; however, there exists only a handful of studies that describe their efficacy for chronic constipation. The purpose of this study is to review the available literature on the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. To fulfil the objectives of the study, published articles in the English language on databases such as Pubmed, Ovid Medline, and EMBASE were searched. The terms prebiotics, constipation, chronic constipation, functional constipation were used. We reviewed and included 21 randomized controlled trials exploring the role of prebiotics in constipated adults. Prebiotics are effective treatments for chronic idiopathic constipation and showed improvement in the stool consistency, number of bowel moments and bloating. Although which prebiotic formulary would promote improved symptoms of constipation is still not clear.

Objective: We aimed to determine the therapeutic drug monitoring (TDM) features and the relation to Brain-Derived Neurotrophic Factor (BDNF) of frequently used new antiepileptic drugs (NADs) including lamotrigine (LTG), oxcarbazepine (OXC), zonisamide (ZNS) and lacosamide (LCM). Moreover, we investigated their effect on the quality of life (QoL).

Methods: Eighty epileptic patients who had been using the NADs, and thirteen healthy participants were included in this cross-sectional study. The participants were randomized into groups. The QOLIE-31 test was used for the assessment of QoL. We also prepared and applied "Safety Test". HPLC method for TDM, and ELISA method for BDNF measurements were used consecutively.

Results: In comparison to healthy participants, epileptic participants had lower marriage rate (p=0.049), education level (p˂0.001), alcohol use (p=0.002). BDNF levels were higher in patients with focal epilepsy (p=0.013) and in those with higher education level (p=0.016). There were negative correlations between serum BDNF levels and serum ZNS levels (p=0.042) with LTGpolytherapy, serum MHD levels (a 10-monohydroxy derivative of OXC, p=0.041) with OXCmonotherapy. There was no difference in BDNF according to monotherapy-polytherapy, drugresistant groups, regarding seizure frequency. There was a positive correlation between total health status and QoL (p˂0.001). QOLIE-31 overall score (OS) was higher in those with OXCmonotherapy (76.5±14.5). OS (p˂0.001), seizure worry (SW, p=0.004), cognition (C, p˂0.001), social function (SF, p˂0.001) were different in the main groups. Forgetfulness was the most common unwanted effect.

Conclusion: While TDM helps the clinician to use more effective and safe NADs, BDNF may assist in TDM for reaching the therapeutic target in epilepsy.

Background: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy.

Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures.

Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group.

Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.

Background: Antibiotic therapies targeting multiple regenerative mechanisms have the potential for neuroprotective effects, but the diversity of experimental strategies and analyses of non-standardised therapeutic trials are challenging. In this respect, there are no cases of successful clinical application of such candidate molecules when it comes to human patients.

Methods: After 24 hours of culturing, three different minocycline (Sigma-Aldrich, M9511, Germany) concentrations (1 μM, 10 μM and 100 μM) were added to the primary cortical neurons 15 minutes before laser axotomy procedure in order to observe protective effect of minocycline in these dosages.

Results: Here, we have shown that minocycline exerted a significant neuroprotective effect at 1 and 100μM doses. Beyond confirming the neuroprotective effect of minocycline in a more standardised and advanced in-vitro trauma model, our findings could have important implications for future studies that concentrate on the translational block between animal and human studies.

Conclusion: Such sophisticated approaches might also help to conquer the influence of humanmade variabilities in critical experimental injury models. To the best of our knowledge, this is the first study showing that minocycline increases in-vitro neuronal cell survival after laser-axotomy.