Higher magnesium levels are associated with better glycaemic control and diabetes remission post-bariatric surgery.

BACKGROUND: Low Magnesium (Mg) dietary intake has been associated with increased risk of type 2 diabetes mellitus (T2DM). Furthermore, in patients with T2DM, hypomagnesemia is associated with worst glycaemic control. Bariatric surgery (BS) remains the most effective treatment in severe obesity and also provides resolution/improvement of T2DM. Our aim is to evaluate the association between Mg supplementation post-BS and Mg serum levels with diabetes status after BS. METHODS: We performed an observational study on patients with obesity and T2DM who underwent BS. Data was assessed pre-BS and one-year post-BS. RESULTS: We included a total of 403 patients with T2DM. At baseline, 43.4% of the patients had Mg deficiency. Pre-BS, patients with Mg deficiency had poorer glycaemic control - HbA1c 7.2 ± 1.6% vs 6.4 ± 1.0% (p < 0.001), fasting plasma glucose 146.2 ± 58.8 mg/dL vs 117.5 ± 36.6 mg/dL (p < 0.001) and were under a greater number of anti-diabetic drugs 1.0 (IQR 0-2.0) vs 1.0 (IQR 0-1.0) (p = 0.002). These findings persisted at one-year post-BS. At the first-year post-BS, 58.4% of the patients had total remission of T2DM and 4.1% had partial remission. Patients without Mg deficiency at one-year post-BS had higher rates of total and partial remission. Higher serum Mg levels at baseline is an independent predictor of total T2DM remission (p < 0.0001). The optimal cut-off of baseline Mg to predict total T2DM remission was 1.50 mg/dL with a sensitivity of 73% and a specificity of 58% (area under ROC = 0.65). Patients that were under Mg supplementation post-BS had serum Mg values, glycaemic control and total remission of T2DM similar to patients non-supplemented. CONCLUSION: In patients with T2DM submitted to BS, higher Mg serum levels at baseline and 1-year after BS were associated with better glycaemic control and higher rates of total T2DM remission at the first year post-BS.

Pruritus in Kidney Disease.

Pruritus is a common and distressing symptom in patients with chronic kidney disease. The most recent epidemiologic data have suggested that approximately 40% of patients with end-stage renal disease experience moderate to severe pruritus and that uremic pruritus (UP) has a major clinical impact, being associated strongly with poor quality of life, impaired sleep, depression, and increased mortality. The pathogenesis of UP remains largely unclear, although several theories on etiologic or contributing factors have been proposed including increased systemic inflammation; abnormal serum parathyroid hormone, calcium, and phosphorus levels; an imbalance in opiate receptors; and a neuropathic process. UP can present somewhat variably, although it tends to affect large, discontinuous, but symmetric, areas of skin and to be most symptomatic at night. A variety of alternative systemic or dermatologic conditions should be considered, especially in patients with asymmetric pruritus or other atypical features. Treatment initially should focus on aggressive skin hydration, patient education on minimizing scratching, and optimization of the aspects of chronic kidney disease care that are most relevant to pruritus, including dialysis adequacy and serum parathyroid hormone, calcium, and phosphorus management. Data for therapy specifically for UP remain limited, although topical therapies, gabapentin, type B ultraviolet light phototherapy, acupuncture, and opioid-receptor modulators all may play a role.

¹H-nuclear magnetic resonance analysis of the triacylglyceride composition of cold-pressed oil from Camellia japonica.

Camellia japonica (CJ) has oil-rich seeds, but the study of these oils has received little attention and has mainly focused only on their health properties. In the present work the relative composition of the fatty acid (FA) components of the triglycerides in cold-pressed oil from CJ is studied by ¹H-NMR. The results obtained were: 75.75%, 6.0%, 0.17% and 18.67%, for oleic, linoleic, linolenic and saturated FA respectively. Levels of C18 unsaturated FA found in CJ oil were similar to those reported for olive oils. We also checked the possibility of using ¹³C-NMR spectroscopy; however, the results confirmed the drawback of ¹³C over ¹H-NMR for the study of FA components of CJ triglycerides due to its low gyromagnetic ratio and its very low natural abundance.

Use of the hollow fiber assay for the evaluation of DNA damaging agents.

INTRODUCTION: The preclinical development and clinical progression of potential anticancer agents are highly time and resource-intensive. Traditionally, promising compounds in vitro undergo further screening in xenograft models, a long process that uses large numbers of animals. In order to hasten compound progression, the hollow fiber assay (HFA) was developed by the US National Cancer Institute as an additional filtering step in drug development, bridging the gap between in vitro and xenograft compound screening. The HFA demonstrates a good correlation in terms of clinical predictivity, and has significant reduction and refinement benefits for animal usage. In addition, the assay enables the study of basic pharmacological properties of compounds under investigation. The HFA has been mainly used as a rapid in vivo cytotoxicity screen, but has also been shown to be amenable to study drug/target interactions in vivo. One of the challenges of the HFA is the small sample sizes obtained, which can limit sensitivity. METHODS: Here we specifically focus on the detection of DNA double-strand breaks, monitoring the effects of standard and novel anti-cancer agents on human lung, colon and breast cancer cell lines using immunoblotting and flow cytometry techniques for γ-H2A.X. This presented a further challenge due to the low abundance of the target event. RESULTS: We found a good correlation between techniques in terms of rate of detection and sensitivity confirming the ability to use the HFA for detection of these specific drug-target interactions. DISCUSSION: The results demonstrate good sensitivity and predictability for drug behavior in an assay where cell number is limited. In contrast to conventional xenograft studies, this short-term assay also enables analysis of pharmacodynamic endpoints in tumor cells in vivo. Importantly, there is a significant impact on reduction and refinement of the use of animals in incorporating this assay into the drug development process.

Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania.

BACKGROUND: This is the first clinical trial comparing the efficacy of artesunate plus amodiaquine (ASAQ) and artemether-lumefantrine (AL)--the major artemisinin-based combination therapy (ACT) candidates for treatment of malaria in Africa--that involved an extended, 42-day follow-up period, polymerase chain reaction-adjusted parasitological cure rates (PCR APCRs), and systematic analyses of genetic markers related to quinoline resistance. METHODS. A total of 408 children with uncomplicated Plasmodium falciparum malaria in Zanzibar, Tanzania, were enrolled. Children who were 6-8 months of age and/or who weighed 6-8 kg were assigned to receive ASAQ for 3 days. Children who were 9-59 months of age and who weighted > or =9 kg were randomly assigned to receive either ASAQ or AL for 3 days in standard doses. Intention-to-treat analyses were performed. RESULTS: Age- and weight-adjusted PCR-APCRs by follow-up day 42 were 91% (188 of 206 patients) in the ASAQ group and 94% (185 of 197 patients) in the AL group (odds ratio [OR] for the likelihood of cure, 2.07; 95% confidence interval [CI], 0.84-5.10; P=.115). A total of 5 and 7 recrudescences occurred after day 28 in the ASAQ and AL groups, respectively. On the assumption that 10 malaria episodes with uncertain PCR results were recrudescences, PCR-APCRs decreased to 88% in the ASAQ group and to 92% in the AL group. Unadjusted cure rates by day 42 were 56% (116 of 206 patients) in the ASAQ group versus 77% (151 of 197 patients) in the AL group (OR, 2.55; 95% CI, 1.66-3.91; P<.001). Rates of reinfection by day 42 were 36% (65 of 181 patients) in the ASAQ arm versus 17% (31 of 182 patients) in the AL arm (OR, 0.37; 95% CI, 0.22-0.60; P<.001). A significant selection of P. falciparum multidrug resistance gene 1 allele 86N was found in isolates associated with reinfection after AL treatment, compared with isolates at baseline (2.2-fold increase; P<.001). CONCLUSIONS: Both treatments were highly efficacious, but AL provided stronger prevention against reinfection. The high proportion of recrudescences found after day 28 and the genetic selection by the long-acting partner drug underlines the importance of long follow-up periods in clinical trials. A long follow-up duration and performance of PCR genotyping should be implemented in programmatic surveillance of antimalarial drugs.

Treatment of chronic pain in adult scoliosis.

INTRODUCTION: One of the most important sequels of scoliosis in adults is pain, caused either by muscular overuse and imbalance or by nerve root compression. This is a very difficult sequel to treat because of the failure of the common analgesic drugs and physiotherapy treatments. MATERIAL AND METHOD: We studied 30 patients with degenerative scoliosis of different origins. There were 24 women and 6 men. Patient age ranged from 25 to 55 years old. The initial Cobb angle ranged from 25 degrees to 65 degrees with a mean of 35 degrees. The mean Schöber back score* at the beginning of treatment was 1.32. The number of sessions with the F.E.D. method were between 20 and 60 with a mean of 45 sessions. All the patients had a case history of NSAIDs, muscle relaxants and physiotherapy. RESULTS: The final average Cobb angle was 33 degrees and Schöber score* 2.88. After treatment, only two cases required NSAIDs, muscle relaxants and physiotherapy. CONCLUSIONS: The F.E.D. method seems to be a promising alternative for treatment of painful sequels in adult scoliosis, since in our study disappearance of symptomatology was seen in the majority of cases. The F.E.D. method also had a permanent effect over time if patients followed a home physiotherapy program. This analgesic effect has a direct relation with the improvement achieved in the flexibility index.