Comparative characteristics between calyculin A-induced and thimerosal-induced hyperactivation of cryopreserved bovine spermatozoa.

This study aimed to characterize calyculin A (CL-A)-induced and thimerosal-induced hyperactivation of cryopreserved bovine spermatozoa. Hyperactivation was effectively induced by treating with 10 nM CL-A for 60 min in the presence of cyclic AMP analogs, extracellular Ca2+, and albumin or with 12.5 µM thimerosal briefly in the absence of these capacitation-supporting factors. Majority of the spermatozoa exhibiting CL-A-induced hyperactivation were characterized by the 3-dimensional helical movement with head rotation, higher degree of flagellar curvature, and faster beating of the flagella than those exhibiting thimerosal-induced hyperactivation of the 2-dimensional planar movement without head rotation. The CL-A-induced hyperactivation was linked to the activation of cAMP/protein phosphorylation-dependent signaling cascades and to the decreased activity of glycogen synthase kinase-3α (GSK-3α). In contrast, the thimerosal-induced hyperactivation was suppressed by pretreatment with CL-A and cyclic AMP analogs in the absence of CaCl2 to activate cAMP/protein phosphorylation-dependent signaling cascades. Additionally, the intracellular Ca2+ level in live sperm flagella was significantly higher in the CL-A-treated samples than in the thimerosal-treated samples. These results indicate that CL-A-induced hyperactivation of cryopreserved bovine spermatozoa is an extracellular Ca2+-dependent type with the 3-dimensional helical movement, which can be regulated not only by the activation of cAMP/protein phosphorylation-dependent signaling cascades, leading to a large enhancement of the intracellular Ca2+ level, but also by the reduction in GSK-3α activity. Considering the different characteristics of thimerosal-induced hyperactivation, our results suggest that the diversity of sperm hyperactivation arises from different combinations of flagellar bending and head rotation.

Evaluation of Bone Metastasis Using Serial Measurements of Serum N-Telopeptides of Type I Collagen in Patients with Lung Cancer: A Prospective Study.

BACKGROUND/AIM: The bone resorption biomarker cross-linked N-Telopeptides of type I collagen (NTx) has been shown to aid in the diagnosis of metastatic bone disease from lung cancer (MBDLC). Patients with MBDLC are often treated with zoledronic acid (ZA). ZA reduces the levels of NTx and also lowers the risk of skeletal adverse events in patients with MBDLC. PATIENTS AND METHODS: Patients with MBDLC at initial diagnosis were included in the study. NTx was measured in serum (sNTx) once a month using the OSTEOMARKTM sNTx assay. MBDLC was assessed by monthly physical examinations and bone scintigraphy every 3 months for 12 months. RESULTS: Twenty patients were enrolled between June and December 2010. The sNTx concentration at baseline was 19.8 ± 5.8 nmol bone collagen equivalents (nmol BCE)/l. In the 16 patients receiving ZA, the level of sNTx significantly decreased after the first month of treatment (baseline vs. 1 month of treatment: 21.3 ± 5.5 vs. 13.6 ± 2.7 nmol BCE/l; p<0.01). During the follow-up period, 13 of the patients treated with ZA experienced worsening of bone metastasis. There were statistically significant differences in the levels of sNTx at baseline (20.3 ± 4.8 nmol BCE/l), at the lowest levels after administration of ZA (11.8 ± 2.9 nmol BCE/l vs. baseline; p<0.001), and at the time of measurable disease progression (14.1 ± 4.6 nM BCE/l vs. baseline; p<0.05). CONCLUSION: Serial measurements of sNTx in patients with MBDLC treated with ZA may effectively predict disease progression.

[A case of a septic pulmonary embolism-related implanted central venous port].

We report a case of a 32-year-old woman with a septic pulmonary embolism-related implanted central venous port. She was treated with S-1/cisplatin(CDDP)chemotherapy for recurrent gastric cancer. Her disease was progressive after five courses of S-1/CDDP combination therapy. Because of peritonitis carcinomatosa, her oral intake was poor, so we placed an implanted central venous port in her right subclavian vein. We administered 5-FU/Leucovorin/paclitaxel combination therapy and total parenteral nutrition from the port. Chemotherapy was effective, so we stopped total parenteral nutrition after one month. Two months later, multiple nodular shadows appeared in her left lung fields without apparent symptoms. Because we suspected septic pulmonary embolism related to the venous port, we removed the venous port promptly and administered antibiotics with a broad spectrum. Pulmonary shadows disappeared immediately, and no recurrence was observed afterward.

Prospective study of urinary and serum cross-linked N-telopeptide of type I collagen (NTx) for diagnosis of bone metastasis in patients with lung cancer.

BACKGROUND: Many cancers metastasize to bone, which may cause an increase in bone resorption because of the direct effects of the tumor itself or osteoclastic activation. PATIENTS AND METHODS: Levels of urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum cross-linked N-telopeptide of type I collagen (sNTx) were measured in 100 patients with lung cancer and 50 patients with benign respiratory disease using the Osteomark NTx urine and serum assays (Osteomark, Princeton, NJ). Bone metastasis was diagnosed by bone scintigraphy. Receiver operating characteristic (ROC) analysis was used to evaluate the detection of bone metastasis. Sensitivity and specificity to detect bone metastasis were calculated when cutoff points were set to 64 nmol bone collagen equivalents (BCE)/mmol Cr for uNTx and 22 nmol BCE/L for sNTx. RESULTS: Patients with lung cancer and bone metastasis had significantly higher levels of both uNTx and sNTx (uNTx median [range], 61.3 [22.7-593.1] nmol BCE/mmol creatinine [Cr]; sNTx median [range], 19.7 [10.7-97.1] nmol BCE/L) than did patients with lung cancer without bone metastasis (uNTx median [range], 45.2 [19.8-153.0] nmol BCE/mmol Cr; sNTx median [range], 16.7 [11.0-28.4] nmol BCE/L), or patients with benign respiratory diseases (uNTx median [range], 40.6 [15.2-155.9] nmol BCE/mmol Cr; sNTx median [range], 14.8 [9.5-55.5] nmol BCE/L.). There was good correlation between uNTx and sNTx (R = 0.807). Area under the curve (AUC) for ROC was 0.743 for uNTx and 0.712 for sNTx. The sensitivity and specificity for the diagnosis of bone metastasis were 48.0% and 86.0%, respectively, using uNTx, and 40.0% and 87.0%, respectively, using sNTx. CONCLUSION: This prospective study indicates equivalency between sNTx and uNTx in sensitivity and specificity to detect bone metastasis, and both uNTx and sNTx may have value as aids in the diagnosis of bone metastasis in patients with lung cancer.