Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand

Background: Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 g/kg, i.m.) or 0.9% NaCl solution (50 L, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 g/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (1000.2 g/ mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 =8 ± 1 g/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 =15 ± 2 g/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom...

Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand

Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 µg/kg, i.m.) or 0.9% NaCl solution (50 µL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 µg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100­0.2 µg/ mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 =8 ± 1 µg/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 =15 ± 2 µg/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom. Conclusions: This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.(AU)

OCT4 expression on a case of poorly differentiated (insular) carcinoma of the thyroid gland and minireview.

Poorly differentiated (insular) carcinoma of the thyroid gland is rare and defined as follicular-cell neoplasms that show limited evidence of structural follicular cell differentiation and occupy both morphologically and behaviourally an intermediate position between differentiated (follicular and papillary carcinomas) and undifferentiated (anaplastic) carcinomas. The authors report a case of a 37-year-old Thai woman who presented with a prolonged left thyroid nodule. Final pathological diagnoses of her mass were poorly differentiated (insular) carcinoma with lymphovascular invasion and nodular goiter. The tumor cell arrangements were nest (insular) and trabecular patterns with some follicular formations. Immunohistochemistry of the tumor cells revealed negative immunostaining for OCT4. Expression of OCT4 gene is involved in the regulation and maintenance of pluripotency of embryonic stem cells, germ cells, and in tumor cells. The authors believe that poorly differentiated (insular) carcinoma of the thyroid gland probably develops from the remnant of thyroid stem cells and is not associated with dedifferentiation (anaplasia or loss of cellular differentiation) from nodular goiter or cells of other thyroid carcinomas. Although there was negative immunostain for OCT4 in the presented case, the authors assumed that the tumor cells behave with an intermediate position between thyroid stem cells and prothyrocytes Also they do not behave with thyroblasts. Additionally, the tumor may be associated with new cellular dedifferentiation. However, there is only one case of immunohistochemistry of OCT4 in poorly differentiated (insular) carcinoma of the thyroid gland. Thus, prognosis of the presented still is mainly correlated with clinical and histological findings. Further research on expression of OCT4 gene on thyroid cancers and other malignant tumors relating to tumorigenic cancer cells (cancer stem cells) may be useful to prognostic evaluation and administration of a new chemotherapy and/or radiotherapy that is specific for tumor-initiating cells.