Low intracellular magnesium in patients with acute pancreatitis and hypocalcemia.

To determine the role of magnesium deficiency in the pathogenesis of hypocalcemia in acute pancreatitis, we measured magnesium levels in serum and in peripheral blood mononuclear cells in 29 patients with acute pancreatitis, 14 of whom had hypocalcemia and 15 of whom had normal calcium levels. Only six patients had overt hypomagnesemia (serum magnesium less than 0.70 mmol per liter [1.7 mg per dl]). The mean serum magnesium concentration in hypocalcemic patients was not significantly lower than in normocalcemic patients, but the mononuclear cell magnesium content in hypocalcemic patients with pancreatitis was significantly lower than in normocalcemic patients with pancreatitis (P less than .01). The serum magnesium level did not correlate with that of serum calcium or the mononuclear cell magnesium content, but the latter did significantly correlate with the serum calcium concentration (r = .81, P less than .001). Most patients with hypocalcemia had a low intracellular magnesium content. Three normomagnesemic, hypocalcemic patients with alcoholic pancreatitis also underwent low-dose parenteral magnesium tolerance testing and showed increased retention of the magnesium load. We conclude that patients with acute pancreatitis and hypocalcemia commonly have magnesium deficiency despite normal serum magnesium concentrations. Magnesium deficiency may play a significant role in the pathogenesis of hypocalcemia in patients with acute pancreatitis.     

Status of thrombocytic-vascular homeostasis in rabbits with parathyroid-depleted hypocalcemia

The experiments on 40 rabbits have revealed the increase in antiaggregation activity of the aortic wall in specific hypocalcemia induced by parathyroid gland removal. Participation of plasmic and vascular factors in the changes of platelet-vascular homeostasis in this pathological condition is discussed.     

Histamine-induced hyperphosphatemia and hypocalcemia in the laying hen

The effects of histamine on plasma inorganic phosphorus (Pi) and total calcium values were studied in laying hens during egg formation and in non-laying hens. Histamine induced hyperphosphatemia and slight hypocalcemia during eggshell calcification, whereas the most pronounced hypocalcemia was observed during the early stages of egg formation. The histamine-induced hyperphosphatemia was completely inhibited by cimetidine but only partly by promethazine. However, the histamine-induced hypocalcemia was totally inhibited by cimetidine and promethazine.     

Effects of hypocalcemia on diaphragmatic strength generation

We studied the effects of hypocalcemia on diaphragmatic force and diaphragm blood flow (Qdi) in 12 anesthetized dogs. The diaphragm was electrically stimulated with intramuscular electrodes surgically implanted in the ventral surface of each hemidiaphragm. The transdiaphragmatic pressure (Pdi) during supramaximal (50 V) 2-s stimulations applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. A catheter was placed via the femoral vein into the left inferior phrenic vein, and Qdi was measured by timed volume collections of left inferior venous effluent. A catheter was introduced in a femoral artery to monitor blood pressure (BP). In five additional dogs, the force generated by the sartorius muscle during electrical stimulation was also studied concomitantly to diaphragmatic force. The animals were mechanically ventilated throughout the experiment, and the arterial blood gases and pH were maintained constant. Hypocalcemia was induced by a continuous infusion of EGTA (70 mg X kg-1 X h-1), which led to a progressive decrease (P less than 0.0001) of ionized calcium plasmatic level from 2.21 +/- 0.4 meq/1 during control to 1.69 +/- 0.06, 1.25 +/- 0.5, and 1.07 +/- 0.5 meq/1 after 30, 60, and 120 min, respectively. Hypocalcemia decreased progressively Pdi, which amounted to 84 +/- 3 (P less than 0.001) and 98 +/- 2% of control values for the low frequencies (10 and 20 Hz) and the high frequencies (50 and 100 Hz), respectively, after 30 min of EGTA infusion and to 74 +/- 5 and 79 +/- 6% for the low and high frequencies, respectively, after 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneity of antibody specificity in Taiwanese patients with polyneuropathy and IgM paraproteinemia

About half of the Caucasian patients with chronic polyneuropathy and IgM paraproteinemia show serum anti-myelin-associated glycoprotein (MAG) and anti-sulfoglucuronosyl glycosphingolipid (SGGLs) activities. These antibody activities have been demonstrated to react with a carbohydrate epitope known as the HNK-1 or sulfoglucuronic acid (SGA) epitope. However, in Asian populations the occurrence of serum anti-SGA activities has been reported to be relatively rare. We investigated 5 cases of chronic polyneuropathy with IgM paraproteinemia from Taiwan and found that 3 of them had high-titer serum anti-SGA (SGGL/MAG) antibody activities. The clinical symptoms of these 3 patients were consistent with sensory dominant polyneuropathy with a severer involvement of the lower limbs than of the upper limbs. Electromyography and nerve conduction studies revealed severe sensory nerve involvement (no response in 3 cases) and moderate slowing of motor conduction velocity (MCV) without conduction block. The decrease in MCV correlated well with anti-SGA antibody titer (less than 30 m/s with the titration of 1:12,800, normal 55–60 m/s). Pathological findings showed active demyelinating polyneuropathy with myelin ovoid and myelinated fiber loss. Our data suggest that anti-SGGL antibody activities may not be very rare among Asian populations. Additionally, there seems an intriguing possibility that the titer of this antibody correlates with the severity of peripheral nerve involvement in patients of demyelinating polyneuropathy with IgM paraproteinemia.     

Up-regulation of hexokinaseII in myeloma cells: targeting myeloma cells with 3-bromopyruvate

Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. However, HKII levels and its roles in ATP production and ATP-dependent cellular process have not been well studied in hematopoietic malignant cells including multiple myeloma (MM) cells.We demonstrate herein that HKII is constitutively over-expressed in MM cells. 3-bromopyruvate (3BrPA), an inhibitor of HKII, promptly and substantially suppresses ATP production and induces cell death in MM cells. Interestingly, cocultures with osteoclasts (OCs) but not bone marrow stromal cells (BMSCs) enhanced the phosphorylation of Akt along with an increase in HKII levels and lactate production in MM cells. The enhancement of HKII levels and lactate production in MM cells by OCs were mostly abrogated by the PI3K inhibitor LY294002, suggesting activation of glycolysis in MM cells by OCs via the PI3K-Akt-HKII pathway. Although BMSCs and OCs stimulate MM cell growth and survival, 3BrPA induces cell death in MM cells even in cocultures with OCs as well as BMSCs. Furthermore, 3BrPA was able to diminish ATP-dependent ABC transporter activity to restore drug retention in MM cells in the presence of OCs. These results may underpin possible clinical application of 3BrPA in patients with MM.