Generation of a unique small molecule peptidomimetic that neutralizes lupus autoantibody activity

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of pathogenic autoantibodies, many of which are directed against nuclear antigens, in particular double-stranded (ds) DNA. Both clinical studies and animal models have shown that anti-dsDNA antibodies contribute to kidney disease, which is present in 50% of lupus patients and is a major cause of mortality. We previously demonstrated that a subset of nephrotoxic anti-dsDNA antibodies also recognizes the pentapeptide consensus sequence D/E W D/E Y S/G (DWEYS) present in the NR2A and NR2B subunits of the N-methyl-d-aspartate receptor (NMDAR). Autoantibodies with this specificity are present in ≈40% of lupus patient sera and are both nephrotoxic and neurotoxic. Elevated titers are present in cerebrospinal fluid of patients with central nervous system manifestations of SLE. Administration of the nonnaturally occurring D form of the DWEYS pentapeptide prevents these antibodies from depositing in glomeruli and from mediating neuronal excitotoxicity. To craft a more useful therapeutic, we used the structural features of the DWEYS peptide to design a unique, selective, and potent small molecule peptidomimetic, FISLE-412, which neutralizes anti-dsDNA/NMDAR lupus autoantibodies and prevents their pathogenic interaction with tissue antigens. This compound, or others derived from it, may provide a unique strategy for the development of lupus therapeutics.     

Comparison of therapeutic effects of garlic and d-Penicillamine in patients with chronic occupational lead poisoning

Abstract: Previous studies on animals have revealed that garlic (Allium sativum) is effective in reducing blood and tissue lead concentrations. The aim of this study was to investigate therapeutic effects of garlic and compare it with d ‐penicillamine in patients with chronic lead poisoning. After coordination and obtaining informed consent, clinical examinations and blood lead concentration (BLC) of 117 workers at a car battery industry were investigated. BLC was determined by heated graphite atomization technique of an atomic absorption spectrometer. The workers were randomly assigned into two groups of garlic (1200 μg allicin, three times daily) and d ‐penicillamine (250 mg, three times daily) and treated for 4 weeks. BLC was determined again 10 days post‐treatment. Clinical signs and symptoms of lead poisoning were also investigated and compared with the initial findings. Clinical improvement was significant in a number of clinical manifestations including irritability (p = 0.031), headache (p = 0.028), decreased deep tendon reflex (p = 0.019) and mean systolic blood pressure (0.021) after treatment with garlic, but not d ‐penicillamine. BLCs were reduced significantly (p = 0.002 and p = 0.025) from 426.32 ± 185.128 to 347.34 ± 121.056 μg/L and from 417.47 ± 192.54 to 315.76 ± 140.00 μg/L in the garlic and d ‐penicillamine groups, respectively, with no significant difference (p = 0.892) between the two groups. The frequency of side effects was significantly (p = 0.023) higher in d ‐penicillamine than in the garlic group. Thus, garlic seems safer clinically and as effective as d ‐penicillamine. Therefore, garlic can be recommended for the treatment of mild‐to‐moderate lead poisoning.     

Effects of age on hemorheological responses to acute endurance exercise

The purpose of this investigation was to examine the effects of age on the acute responses of hemorheological variables and biochemical parameters to a single bout of sub-maximal endurance exercise. Fifteen young (20-30 years), 15 middle-aged (40-50 years) and 12 old (60-70 years) male subjects participated in the study. All subjects performed one single bout of endurance exercise encompassed 30-min cycling at 70-75% of maximal heart rate which was followed by 30-min recovery. Three blood samples were taken before, immediately after exercise and after 30-min recovery. Resting levels of hematocrit, red blood cells count, plasma albumin and fibrinogen concentrations, plasma viscosity and whole blood viscosity were significantly different among the three groups (P < 0.01). Thirty minutes of cycling resulted in significant increases (P < 0.05) in all parameters; while these changes were temporary and returned to pre-exercise level at the end of recovery. Responses of all parameters to exercise and recovery were not significantly different among the three groups (P > 0.05). Fibrinogen changes during exercise and recovery were corrected for exercise- and recovery-induced changes in plasma volume. Data analysis showed effects of exercise and recovery only for raw data (P > 0.05). In addition, raw and corrected fibrinogen data in response to exercise and recovery were not age-related. Our results demonstrate that age does not affect the hemorheological responses to an acute endurance exercise in healthy men.     

Neurocysticercosis in Qatari patients: case reports

Neurocysticercosis is the most common parasitic infection of the central nervous system. It is a major cause of seizures in developing countries, especially in the Indian subcontinent and most of Asia, Latin America and Africa. It is increasing in prevalence in Muslim countries, especially in the Gulf region reflecting the demographics of these countries which rely heavily on labourers from highly endemic areas. Infections among Muslims in non-endemic regions are increasing. We describe one prospective case report of a Qatari male who presented with seizures and was found to have neurocysticercosis, and three retrospective cases of this infection among Qatari Muslims, who were admitted to a tertiary care hospital over the past 10 years.     

Percutaneous treatment of bladder stones in children: 10 years experience, is blind access safe?

Purpose

Bladder stones are more commonly found in children from developing countries. Open cystolithotomy or transurethral cystolithalopaxy are the traditional treatments but a percutaneous approach has been advocated. We present our experience with percutaneous cystolithotomy in children with bladder stones without any ultrasonic or fluoroscopic guidance.

Materials and method

From April 2001 to October 2011, a total of 147 children (135 boys and 12 girls) with a mean (range) age of 4.07 (1–12.5) years underwent percutaneous cystolithotripsy (PCCL). The mean (range) stone diameter was 2.74 (0.8–5) cm. 138 children (94 %) had a solitary stone while nine (6 %) had more than one stone. The main component of the stones was calcium oxalate in 70 patients (48.6 %).

Results

All children were stone-free after one PCCL; no recurrent stones developed. The mean (range) PCCL procedure time was 29.6 (12 to 48) min and intraoperative blood loss was scant. Perioperative complications were few. The mean (range) hospital stay was 1.2 (1–3) days.

Conclusions

Blind access PCCL (without any ultrasonic or fluoroscopic guidance) is a facile and safe approach for removing stones in the pediatric bladder stones. Advantages include the lack of ionizing radiation, no need for opacification by iodine contrast media and low relative cost. We recommend this minimally invasive technique for management of large bladder stones (larger than 1 cm) in children. To our knowledge, this is the largest single-center series reported on percutaneous cystolithotripsy of endemic bladder stones in children.     

Mercury Contamination of Fish and Shrimp Samples Available in Markets of Mashhad, Iran

Fish and shrimp are common healthy sources of protein to a large percentage of the world’s population. Hence, it is vital to evaluate the content of possible contamination of these marine-foods. Six species of fishes and two species of shrimps were collected from the local markets of Mashhad, Iran. The mercury (Hg) concentration of samples was determined by atomic absorption spectrophotometry using a mercuric hydride system (MHS 10). High concentration of total Hg was found in Clupeonella cultriventris caspia (0.93 ± 0.14 μg/g) while the lowest level was detected in Penaeus indicus (0.37 ± 0.03 μg/g). Mean Hg levels in fish and shrimp samples were 0.77 ± 0.08 μg/g and 0.51 ± 0.05 μg/g, respectively. Farmed species (except for P. indicus) and all samples from Persian Gulf and the Caspian Sea had mean mercury concentrations above 0.5 μg/g, which is the maximum standard level recommended by Joint FAO/WHO/Expert Committee on Food Additives (JECFA). All samples had also mean Hg concentrations that exceeded EPA’s established safety level of 0.3 μg/g. A little more extensive analysis of data showed that weekly intake of mercury for the proportion of the Iranian population consuming Hg contaminated fish and shrimp is not predicted to exceed the respective provisional tolerable weekly intakes recommended by JECFA. However, the Iranian health and environmental authorities should monitor Hg contamination of the fishes and shrimps before marketing.     

The effect of vitamin A on renal damage following acute pyelonephritis in children

Animal studies suggest that administration of vitamin A to rats with experimental urinary tract infection decreases the frequency of renal scars (Kavukçu et al., BJU Int 83(9):1055–1059, 1999). The aim of this study was to determine the effect of vitamin A on the rate of permanent renal damage in children with acute pyelonephritis. Fifty children, median age of 24 months (range 2–144), with first-time pyelonephritis verified by an uptake defect on acute dimercaptosuccinic acid (DMSA) scan were included in the study and randomly allocated to the case or control groups. All were given intravenous ceftriaxone for 10 days followed by oral cephalexin for 3 months. Cases in addition were given a single intramuscular dose of vitamin A, 25,000 U for infants below 1 year of age and 50,000 U for older children. At the repeat DMSA scan after 3 months, five of 25 cases (20%) and 17 of 25 controls (68%) had abnormal findings (p?=?0.001). In conclusion, administration of vitamin A was associated with a significantly lower rate of permanent renal damage.