KTt-45, a T-type calcium channel blocker, acts as an anticancer agent by inducing apoptosis on HeLa cervical cancer cell line.

The abnormal expression in the T-type calcium channels is involved in various cancer types, thus inhibiting T-type calcium channels is one of approaches in cancer treatment. The fact that KTt-45 acted as a T-type calcium channel inhibitor as well as a pain-relief agent prompts us to address if KTt-45 plays any role against cancer cells. The results showed that KTt-45 caused cytotoxic effects towards HeLa cervical, Raji lymphoma, MCF-7 breast cancer, and A549 lung cancer cell lines with IC50 values less than 100 µM, in which highly selective toxicity was against HeLa cells (IC50 = 37.4 µM, SI > 3.2). Strikingly, the KTt-45 induced an accumulation of cytoplasmic vacuoles after 48 h treatment and mitochondrial-dependent apoptosis activation as evidenced by morphological features, chromatin condensation, nuclear fragmentation, and significant activation of caspase-9 as well as caspase-3. In conclusion, KTt-45 could inhibit cell growth and trigger mitochondrial-dependent apoptosis in HeLa cervical cancer cells. The results, taken together, strongly demonstrated that KTt-45 is a potential agent for further study on anticancer drug development which not only targets cancer cells but also helps to relieve neuropathic pain in cancer patients.

Bach Mai Procedure for complete mesocolic excision, central vascular ligation, and D3 lymphadenectomy in total laparoscopic right hemicolectomy: a prospective study.

PURPOSE: Total laparoscopic right hemicolectomy with complete mesocolic excision (CME), central vascular ligation (CVL), and D3 lymphadenectomy is still the most challenging colon procedures for gastrointestinal surgeons. We herein report the technical details and our preliminary experience of Bach Mai Procedure - a novel-combining (cranial, medial to lateral, and caudal) approach with early resection of the terminal ileum. METHODS: The dissection stage was central vascular isolation and ligation by a combined multiple approaches in the following four steps: cranial approach, dissecting along the inferior aspect of pancreatic isthmus to reveal the middle colic vessels and the anterior aspect of the superior mesentery vein and then exposed the right gastroepiploic vein and the trunk of Henle; medial-to-lateral approach, exposing the surgical axis - the superior mesenteric vascular axis and then early resection of the terminal ileum to open the dissection from the bottom up; and caudal approach, radical ligation of the ileocecal artery and right colic artery (central vascular ligation), lymph node dissection (D3 lymphadenectomy), and resecting the Toldt fascia of the colon to release the entire right colon from the abdominal wall. RESULTS: In 12 months, there were 32 cases of primary right-sided colon malignancies that have undergone tLRHD3, CME/CVL based on the Bach Mai Procedure. In 3 cases (9.4%), the tumor site was hepatic flexure. The median of lymph node number (LNN) was 38, with the maximum number which was 101. No serious postoperative complications (grade 3 or higher) neither inhospital mortality was detected. CONCLUSION: This Bach Mai procedure, a novel-combining approach with early resection of the terminal ileum, is technically feasible and safe for tLRHD3, CME/CVL. Further investigations and follow-up must be proceeded to evaluate the long-term outcomes of our technique.

The novel small-molecule antagonist of PAC1 receptor attenuates formalin-induced inflammatory pain behaviors in mice.

We recently developed PA-8, a novel small-molecule antagonist of PACAP type 1 (PAC1) receptor. In the present study, we examined whether PA-8 was effective against formalin-induced inflammatory pain in mice. Both intrathecal and oral administration of PA-8 resulted in the dose-dependent attenuation of the second phase of formalin-induced nociceptive responses. PA-8 also inhibited c-fos upregulation in the ipsilateral dorsal horn of the spinal cord. The results suggested that PACAP-PAC1 receptor signaling system in the spinal cord were primarily involved in the transmission of inflammatory pain, and PA-8 could be useful for the development of novel analgesics for treating inflammatory pain.

Design and synthesis of novel anti-hyperalgesic agents based on 6-prenylnaringenin as the T-type calcium channel blockers.

Since 6-prenylnaringenin (6-PNG) was recently identified as a novel T-type calcium channel blocker with the IC50 value around 1 µM, a series of flavanone derivatives were designed, synthesized and subsequently evaluated for T-channel-blocking activity in HEK293 cells transfected with Cav3.2 T-type channels using a patch-clamp technique. As a result, several new flavanones blocked Cav3.2-dependent T-currents more potently than 6-PNG. In the synthesized compounds, 6-(3-ethylpent-2-enyl)-5,7-dihydroxy-2-(2-hydroxyphenyl)chroman-4-one 8j, 6-(3-ethylpent-2-enyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one 11b, 6-(2-cyclopentylideneethyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one 11d, and 6-(2-Cyclopentylethyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one 12c were more potent blocker than 6-PNG with the IC50 value of 0.39, 0.26, 0.46, and 0.50 µM, respectively. Among the above four derivatives, the compound 8j provided the best result in the in vivo experiments; i.e. systemic administration of 8j at the minimum dose completely restored neuropathic pain induced by partial sciatic nerve ligation in mice.

Maternal health care utilization in Viet Nam: increasing ethnic inequity.

OBJECTIVE: To investigate changes that took place between 2006 and 2010 in the inequity gap for antenatal care attendance and delivery at health facilities among women in Viet Nam. METHODS: Demographic, socioeconomic and obstetric data for women aged 15-49 years were extracted from Viet Nam's Multiple Indicator Cluster Survey for 2006 (MICS3) and 2010-2011 (MICS4). Multivariate logistic regression was performed to determine if antenatal care attendance and place of delivery were significantly associated with maternal education, maternal ethnicity (Kinh/Hoa versus other), household wealth and place of residence (urban versus rural). These independent variables correspond to the analytical framework of the Commission on Social Determinants of Health. FINDINGS: Large discrepancies between urban and rural populations were found in both MICS3 and MICS4. Although antenatal care attendance and health facility delivery rates improved substantially between surveys (from 86.3 to 92.1% and from 76.2 to 89.7%, respectively), inequities increased, especially along ethnic lines. The risk of not giving birth in a health facility increased significantly among ethnic minority women living in rural areas. In 2006 this risk was nearly five times higher than among women of Kinh/Hoa (majority) ethnicity (odds ratio, OR: 4.67; 95% confidence interval, CI: 2.94-7.43); in 2010-2011 it had become nearly 20 times higher (OR: 18.8; 95% CI: 8.96-39.2). CONCLUSION: Inequity in maternal health care utilization has increased progressively in Viet Nam, primarily along ethnic lines, and vulnerable groups in the country are at risk of being left behind. Health-care decision-makers should target these groups through affirmative action and culturally sensitive interventions.