Benzyl isothiocyanate-induced DNA damage causes G2/M cell cycle arrest and apoptosis in human pancreatic cancer cells

Benzyl isothiocyanate (BITC) has been shown to inhibit chemically induced pancreatic cancer in experimental animals. However, the mechanism responsible for the anticancer effects of BITC is not clearly understood. In this study, we tested whether BITC treatment would affect the growth of Capan-2 human pancreatic cancer cells. BITC (10 micromol/L) treatment caused marked phosphorylation of H2A.x (2.6-fold) and permanent damage to Capan-2 cells. BITC-mediated G2/M arrest was associated with up-regulation of cyclin dependent kinase inhibitor p21(Waf1/Cip1) and the activation of checkpoint kinase 2, whereas the expressions of other G2/M regulatory proteins, including CyclinB1, Cdc2, and cell division cycle 25C (Cdc25C), were down-regulated by 19, 51, and 70%, respectively, compared with control. These changes resulted in a 55% inhibition of Cdc2 kinase activity. In addition, the decline in the expression of Cdc25C was completely blocked when the cells were treated with lactacystin (proteasome inhibitor) prior to BITC treatment. However, G2/M arrest and apoptosis induced by BITC were partially blocked by pretreatment of cells with lactacystin. Taken together, the results of this study suggest the involvement of multiple signaling pathways targeted by BITC in mediating G2/M cell cycle arrest and apoptosis in Capan-2 cells and warrant further investigation.     

Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients

Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI‐specific genes and correlate these with phenotypes. COL1A1 and COL1A2 gene variants were identified in 44.23%, of which 28.84% were glycine substitution abnormalities. Two novel compound heterozygous variants in the FKBP10 gene were seen in two unrelated probands. A novel heterogeneous duplication of chromosomal region chr17: 48268168–48278884 from exons 1–33 of the COL1A1 gene was found in one proband. In five probands, there were additional variants in association with OI. These were ANO5 in association with CRTAP in two probands of the same family causing gnathodiaphyseal dysplasia, COL5A2 with LEPRE1 causing Ehlers Danlos syndrome, COL11A1 in addition to COL1A1 causing Stickler syndrome, and a previously unreported combination of SLC34A1 gene variant with FKBP10 leading to Fanconi renal tubular syndrome type II. Our findings demonstrate the efficacy of clinical exome sequencing in screening OI patients, classifying its subtypes, and identifying associated disorders in consanguineous populations.     

Novel stretchable thermochromic transparent heaters designed for smart window defroster applications by spray coating silver nanowire

A productive and novel method for fabricating stretchable transparent heaters with recognised thermochromic properties using commercially available thermochromic ink (TM-55-blue) and silver nanowire (AgNW)-coated polydimethylsiloxane (PDMS) is proposed. Lower resistance, elevated heat generation, and higher transparencies were the expected essential prerequisites for the fabrication of items such as smart windows and window defrosters. AgNW-coated PDMS (hereafter PH devices) satisfied the essential prerequisites but did not produce sufficient color change. In addition to the appreciable electrical and optical characteristics and mechanical robustness, observable color changes represent a critical factor in effortless temperature monitoring by the heating device. Blending TM-55-blue thermochromic ink with PDMS (PBH device) improves the heating rate and color transformation and promotes the ultralow response time appreciably. More notably, it produces a visible transformation from blue to colorless. Color changes visible to the naked eye, ultralow response time, and heating rate represent valuable features for deploying the PBH devices as window defrosters and in smart window applications.

The as-designed heaters proved to be excellent candidates for employment in window defrosters, as they satisfy the essential prerequisites such as lower sheet resistance, high transparency, mechanical robustness and good stability to tensile strain.     

A retrospective study reviewing the fate of the rectum after total abdominal colectomy and end ileostomy in patients with ulcerative colitis

Aim

The objective of this study was to review the fate of the rectal stump following total colectomy for ulcerative colitis and evaluate the risk of rectal cancer.

Methods

A review of operative and pathological databases identified 103 patients who had undergone total abdominal colectomy for ulcerative colitis between 1987 and 2008. Those who had synchronous colorectal cancer at the time of operation were excluded from study.

Results

Twenty of the 103 patients did not proceed with further surgery, most of whom are under regular surveillance of the remaining stump. Ten patients were lost to follow-up. Seventy-three patients were finally included in the study: forty-three patients had been submitted to proctectomy and ileoanal pouch surgery with a success rate of 86%, 28 to proctectomy and ileostomy, and two patients to ileorectal anastomosis.

Conclusion

These data suggest that after a total colectomy, the majority of patients proceed with restorative pouch surgery with encouraging results and for the most part, good quality of life, while a significant number of patients prefer to proceed with completion proctectomy. For those who decide to retain the rectal stump, the incidence of rectal cancer is sufficiently high as to require regular surveillance.     

Comparison of Efficacy of Methylprednisolone Injection into Masseter Muscle Versus Gluteal Muscle for Surgical Removal of Impacted Lower Third Molar

Purpose

To compare the efficacy, advantages and disadvantages of the use of preoperative injection of methylprednisolone into masseter muscle versus gluteal muscle to minimize postoperative swelling after the surgical removal of lower third molar.

Materials and Methods

A prospective randomized study was planned comprising of 10 subjects, undergoing elective surgery for bilateral impacted lower third molar removal with similar severity index. The subjects were randomly assigned into two groups—group I who received intrabuccal masseteric injection and group II who received gluteal injection of 40 mg of methylprednisolone after inferior alveolar nerve and long buccal nerve block (prior to the surgical removal of the impacted lower third molars). We evaluated the postoperative pain, trismus, swelling, advantages and disadvantages of the injection techniques. Statistical analysis was done using student t test.

Results

Ten patients of mean age 27 ± 6 years were selected for the study including six males and four females. The mean age was 27 years (SD 6). The differences in measurements of preoperative and postoperative pain, swelling and mouth opening between group I and group II were not statistically significant.

Conclusion

The study evidently proves that there is no statistically significant difference between the intrabuccal approach of masseteric injection and gluteal injection of methylprednisolone in terms of pain, swelling and trismus following surgical removal of impacted lower third molars. However, the intrabuccal approach of masseteric injection was found to be more convenient when compared to gluteal injection, for the surgeon as well as the patient. It also has an additional advantage of being a painless steroidal injection on an anesthetized injection site.