Protective effect of magnesium-25 carrying porphyrin-fullerene nanoparticles on degeneration of dorsal root ganglion neurons and motor function in experimental diabetic neuropathy

Diabetic neuropathy (DN) is the most common peripheral neuropathy and long-term complication of diabetes. In view of the pathological basis for the treatment of DN, it is important to prevent nerve degeneration. Most of the current treatment strategies are symptomatic therapies. In this study, we evaluated the effectiveness of magnesium-25, carrying porphyrin-fullerene nanoparticles, on diabetes-induced neuropathy. Previous studies have suggested that dorsal root ganglion (DRG) neurons comprise a specific target and may be responsible for the known complications of DN. Experimental DN was induced by intraperitoneal injection of streptozotocin (STZ) (45 mg/kg). Different forms of magnesium including (25)Mg-PMC16, (24)Mg-PMC16 and MgCl(2) were administered intravenously in equal dose (0.5 LD(50)) at 48-hr intervals before STZ injection. Peripheral nerves were studied after 2 months of diabetes in groups using qualitative approaches, morphometric analysis of DRG neurons and motor function tests. We showed that STZ-induced DN caused morphological abnormalities in DRG neurons comprising changes in area, diameter and number of A and B cells as well as motor dysfunction in DN. Moreover, our findings indicated that administration of (25)Mg-PMC16 as a magnetic form of Mg improved morphological abnormalities and motor dysfunctions significantly, whereas other forms of Mg were ineffective.     

A rare electrocardiographic manifestation of a rare form of multiple electrolyte disturbances: hyperparathyroid crisis

The surface electrocardiogram (ECG) has been used as a useful method for detection of metabolic disturbances for a long time. However, it may be difficult to distinguish the exact disturbance when more than one metabolic abnormality exists in a patient simultaneously. Although, "classic" ECG characterizations of common electrolyte disturbances are well described, multiple concurrent electrolyte disturbances may lead to ECG abnormalities that may not be easily detectable. This ECG concerns a 60-year-old male presented with general fatigue, weakness, epigastric pain, anorexia, nausea and extreme hypercalcemia (serum total and ionized calcium levels 20.5 mg/dL and 12.02 mg/dl, respectively), hypokalemia and hypomagnesemia associated with elevated parathyroid hormone (1160 pg/ml) and normal serum vitamin D level (97 ng/ml) . This rare manifestation of primary hyperparathyroidism has been named hyperparathyroid crisis in the literature. Hyperparathyroid crisis is an emergency form of multiple electrolyte abnormalities that manifest as a life-threatening hypercalcemia and simultaneous hypokalemia and hypomagnesemia; these two later are believed to be caused by diuretic effect of calcium on the renal tubules. The unique pattern of ECG in our patient first was misdiagnosed as prominent T waves with prolongation of the QT corrected (QTc) interval, which has been reported several times in patients with hyperparathyroidism crisis, compatible with our patient. But more investigation revealed that, the QTc interval not only is not prolonged, it is shortened as it is expected from the effect of hypercalcemia on electrocardiogram. The exact pattern of the patient`s ECG (figure 1) can be interpreted as it follows: (1) Flattening of the T wave, (2) a prominent U wave, (3) prolongation of the descending limb of the T wave such that it overlapped with the next U wave (4) virtual absence of ST segment and (5) shortening of the QT corrected interval. In conclusion, it should be emphasized when the T and U waves are separated by a very short segment they can mimic the appearance of a prolonged QT interval. However, more investigation can demonstrate the exact electrocardiographic pattern especially in multiple electrolyte disturbances, when "classic" ECG patterns are not expectable.     

Functional expression of electrogenic sodium bicarbonate cotransporter 1 (NBCe1) in mouse cortical astrocytes is dependent on S255-257 and regulated by mTOR

The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major bicarbonate transporter expressed in astrocytes. It is highly sensitive for bicarbonate and the main regulator of intracellular, extracellular, and synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, the molecular mechanisms underlying NBCe1-mediated astrocytic response to extracellular pH changes are mostly unknown. Using primary mouse cortical astrocyte cultures, we investigated the effect of long-term extracellular metabolic alkalosis on regulation of NBCe1 and elucidated the underlying molecular mechanisms by immunoblotting, biotinylation of surface proteins, intracellular H⁺ recording using the H⁺-sensitive dye 2′,7′-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, and phosphoproteomic analysis. The results showed significant downregulation of NBCe1 activity following metabolic alkalosis without influencing protein abundance or surface expression of NBCe1. During alkalosis, the rate of intracellular H⁺ changes upon challenging NBCe1 was decreased in wild-type astrocytes, but not in cortical astrocytes from NBCe1-deficient mice. Alkalosis-induced decrease of NBCe1 activity was rescued after activation of mTOR signaling. Moreover, mass spectrometry revealed constitutively phosphorylated S255-257 and mutational analysis uncovered these residues being crucial for NBCe1 transport activity. Our results demonstrate a novel mTOR-regulated mechanism by which NBCe1 functional expression is regulated. Such mechanism likely applies not only for NBCe1 in astrocytes, but in epithelial cells as well.     

Taurine ameliorates cytotoxic effects of Di(2-ethylhexyl) phthalate on Leydig cells

It has been revealed that di(2-ethylhexyl)phthalate (DEHP) has toxic impacts on the male reproductive system. Taurine (TAU) is an amino acid with antioxidant property and beneficial impacts on the male reproductive system. In this study, protective impacts of Taurine (TAU) on DEHP-induced Leydig TM3 cell toxicity were investigated. The cells exposed to DEHP (0.8 µmol) or TAU (100 mg/ml) for 24 hr. Cell viability (MTT assay), apoptosis, oxidative stress and testosterone level were examined. DEHP could significantly decrease the cell viability percentage, reduce testosterone level, increase apoptosis, elevate Bax/ Bcl-2 ratio and enhance caspase-3 and -9 activity in the TM3 cells. Additionally, DEHP significantly elevated malondialdehyde contents and reactive oxygen species levels. It also augmented superoxide dismutase and catalase activity in the Leydig cells. Co-treatment of DEHP with TAU increased viability and testosterone level, while oxidative stress and apoptosis significantly reduced. TAU could decrease Bax/Bcl-2 ratio and caspase-3 and -9 activity in the DEHP-intoxicated cells. Our results have clearly shown that TAU protects TM3 cells against oxidative stress and apoptosis induced by DEHP.     

Comparison of MR enterography and histopathology in the evaluation of pediatric Crohn disease

Background

While MR enterography (MRE) is commonly used to identify segments of bowel affected by Crohn disease in children, there is little data to support this practice.

Objective

To assess the ability of MRE to identify segments of small bowel and colon affected by pediatric Crohn disease using histopathology as the reference standard.

Materials and methods

Pediatric MRE examinations performed between April 2009 and December 2010 were identified. Subjects were excluded if they did not have Crohn disease, if they had Crohn disease but no correlative histopathology within 2?months of imaging, or if they had undergone prior bowel resection. Pertinent MRE and histopathology reports were reviewed, and normal and abnormal bowel segments were documented.

Results

Thirty-two pediatric MRE examinations were identified with correlative histopathology. MRE had an overall sensitivity of 94% for detecting the presence of Crohn disease, in general. At the bowel segmental level, MRE had a sensitivity of 66%, specificity of 90%, positive predictive value of 85% and negative predictive value of 76%. The terminal ileum was abnormal by MRE in 11 of 15 (73%) subjects lacking a diagnostic biopsy of this bowel segment.

Conclusion

MRE successfully identifies small bowel and colon segments affected by pediatric Crohn disease.     

Oral Verruciform Xanthoma Associated with Chronic Graft-Versus- Host Disease: A Report of Five Cases and a Review of the Literature

Verruciform xanthoma (VX) is an uncommon benign inflammatory mucocutaneous condition that chiefly occurs in the oral cavity. It is often associated with pre-existing epithelial and/or inflammatory disorder and is characterized histopathologically by papillary epithelial hyperplasia and the presence of foamy macrophages in connective tissue papillae. We report of a series of five cases with VX who concurrently had chronic oral graft-versus-host disease following hematopoietic stem cell transplantation.