Hypomagnesemia in diabetes patients: comparison of serum and intracellular measurement of responses to magnesium supplementation and its role in inflammation.

PURPOSE: In this clinical trial, we assessed the efficacy of magnesium (Mg) supplementation in hypomagnesemic type 2 diabetes patients in restoring serum and intracellular Mg levels. The study had two coprimary end points: the change in serum and intracellular Mg level between baseline and after 3 months of supplementation. We compared the efficacy with regard to lowering hemoglobin A1c (HbA1c), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and 8-isoprostane as secondary end points. PATIENTS AND METHODS: In an open-label trial, 47 hypomagnesemic type 2 diabetes patients were administered 336 mg Mg daily. At baseline and after 3 months, serum, cellular Mg, and inflammation biomarkers were measured. For intracellular Mg levels, sublingual epithelial cells were analyzed by analytical scanning electron microscopy using computerized elemental X-ray analysis. Blood samples were analyzed for Mg, creatinine, HbA1c, and CRP. Systemic inflammatory markers including TNF-α and the oxidative stress marker 8-isoprostane were determined using enzyme-linked immunosorbent assay. RESULTS: Mg supplementation significantly increased the intracellular and serum levels. Statistically clinical improvement in HbA1c and CRP levels was not observed, but significant decreases in TNF-α as well as in 8-isoprostane were found. CONCLUSION: A feasible clinical method for the assessment of intracellular Mg was demonstrated in tissue samples obtained noninvasively, providing evidence for potential clinical translation of this method to routinely determine intracellular Mg concentration.

Prevalence of chronic pain with neuropathic characteristics: a randomized telephone survey among medical center patients in Kuwait.

BACKGROUND: Chronic pain with neuropathic characteristics is considered to be an international health problem. However, surveys on the actual incidence of neuropathic pain have not been conducted in many Middle East countries, including Kuwait. The aim of this study was to examine the incidence of pain and medical comorbidities among a random sample of patients treated at a large medical center in Kuwait. METHODS: A list of 1,000 patients was created from the hospital medical record system, and a telephone survey was conducted on 759 patients who responded to the phone call, of which 67.2% (N=510) participated. Those who stated that they had pain every day for the past 3 months were invited to answer additional questions about their pain. RESULTS: Fifty-six percentage of those surveyed (N=283) reported experiencing chronic pain. Total average age was 49.2 years (SD=14.5), 45.5% were female, and 70.5% were Kuwaiti nationals. Most (74.3%) reported having diabetes and one-third (32.2%) showed evidence of neuropathic pain characteristics (mean DN4=2.8, SD=1.7). Other comorbid medical conditions were prevalent (48.4% hypertension, 30.4% arthritis, 22.6% heart disease, and 20.4% asthma) with an average of 2.3 (SD=1.3) medical problems per person. Those with pain tended to be older, female, unemployed, and overweight (p<0.01). The pain was mostly located in the lower extremities and those with neuropathic pain tended to report a higher intensity of pain and a higher frequency of seeking treatment for their pain in a clinic or hospital (p<0.05). Most relied on over-the-counter medications for their pain (38.1%). Very few were taking prescription medication for their pain. CONCLUSION: This survey suggests that chronic pain is more prevalent in a medical population in Kuwait than previously anticipated. Health care services and behavioral interventions to improve lifestyle changes in Kuwait and other Arab countries are needed to positively impact pain and reduce other comorbidities.

Interaction of osteopontin with IL-18 in obese individuals: implications for insulin resistance.

BACKGROUND/OBJECTIVE: Osteopontin (OPN) and IL-18 are known inflammatory mediators and both participate in a wide range of biological processes linked to immunological disorders. Since an interaction between OPN and IL-18 has not been studied in obesity, we investigated whether: (i) their levels were simultaneously elevated in obese individuals; (ii) OPN was associated with IL-18 in obese individuals and (iii) their levels associated with fasting blood glucose (FBG) and BMI. SUBJECTS AND METHODS: PBMCs and plasma samples were isolated from 60 individuals including lean as well as overweight and obese individuals. Subcutaneous adipose tissue samples were obtained. OPN and IL-18 were measured by ELISA. OPN and IL-18 mRNA expression was quantified by real time quantitative RT-PCR. RESULTS: Obese individuals exhibited significantly increased circulating OPN levels as compared with lean individuals (obese 2865±101; lean 1681±116 pg/ml; P<0.0001). IL-18 levels were also high in obese individuals (obese 491±39, lean 301±26 pg/ml; P = 0.0009). OPN and IL-18 expression were simultaneously up-regulated (OPN: 5.4-Fold; IL-18: 8.9-Fold; P<0.05) in PBMCs from obese individuals compared to lean group. Adipose tissue from obese individuals had high expression of OPN (7.3-Fold) and IL-18 (9.6-Fold). Plasma OPN levels correlated positively with FBG levels (r = 0.32, P = 0.02). Similarly, IL-18 correlated positively with FBG levels (r = 0.406, P = 0.0042). Stepwise multiple regression analysis showed an independent association of BMI with OPN and IL-18. Interestingly, OPN levels increased progressively with an increase in IL-18 levels (r = 0.52, P = 0.0004). We also examined the regulatory role of IL-18 in OPN secretion from PBMCs. Neutralizing anti-IL-18Rα mAb reduced OPN secretion. CONCLUSION: These findings represent the first observation that plasma, PBMC and adipose tissue OPN and IL-18 are simultaneously increased and correlate with each other in overweight/obese individuals which may trigger the development of obesity-associated insulin resistance. Moreover, these results provide the direct evidence that IL-18 regulates OPN production in PBMCs.

Quality of Cell Products: Authenticity, Identity, Genomic Stability and Status of Differentiation.

Cellular therapies that either use modifications of a patient's own cells or allogeneic cell lines are becoming in vogue. Besides the technical issues of optimal isolation, cultivation and modification, quality control of the generated cellular products are increasingly being considered to be more important. This is not only relevant for the cell's therapeutic application but also for cell science in general. Recent changes in editorial policies of respected journals, which now require proof of authenticity when cell lines are used, demonstrate that the subject of the present paper is not a virtual problem at all. In this article we provide 2 examples of contaminated cell lines followed by a review of the recent developments used to verify cell lines, stem cells and modifications of autologous cells. With relative simple techniques one can now prove the authenticity and the quality of the cellular material of interest and therefore improve the scientific basis for the development of cells for therapeutic applications. The future of advanced cellular therapies will require production and characterization of cells under GMP and GLP conditions, which include proof of identity, safety and functionality and absence of contamination.