Chimeric Small Molecules for Detouring Drugs into Mitochondria to Engender Apoptosis in Cancer Cells.

Mitochondrion has appeared as one of the important targets for anti-cancer therapy. Subsequently, small molecule anti-cancer drugs are directed to the mitochondria for improved therapeutic efficacy. However, simultaneous imaging and impairing mitochondria by a single probe remained a major challenge. To address this, herein Chimeric Small Molecules (CSMs) encompassing drugs, fluorophore and mitochondria homing moiety were designed and synthesized through a concise strategy. Screening of the CSMs in a panel of cancer cell lines (HeLa, MCF7, A549, and HCT-116) revealed that one of the CSMs comprising Indomethacin V exhibited remarkable cervical cancer cell (HeLa) killing (IC50 =0.97 µM). This lead CSM homed into the mitochondria of HeLa cells within 1 h followed by mitochondrial damage and reactive oxygen species (ROS) generation. This novel Indomethacin V-based CSM-mediated mitochondrial damage induced programmed cell death (apoptosis). We anticipate these CSMs can be used as tools to understand the drug effects in organelle chemical biology in diseased states.

Modern strategies for the anesthetic management of the patient with diabetes.

Diabetes Mellitus (DM) is an endocrine disease with high incidence. Long-term complications involve the eyes, kidneys, nerves, and blood vessels, resulting in hypertension, cardiac ischemia, atherosclerosis, and renal failure, among other syndromes. Given this prevalence, anesthesiologists, especially those who work with older patients, may expect to encounter some aspect of diabetes almost every day. Appropriate preoperative evaluation and rational intraoperative and postoperative management of this complex disease in elective and emergency circumstances are essential. Recent studies have emphasized the need to maintain tight perioperative glycemic control and new guidelines have been presented.

Current perioperative management of the patient with HIV.

Although modem medical care and current therapies save and prolong the lives of many patients with HIV/AIDS, the disease process has no cure and will continue to present itself during the perioperative period. All ages, young and old, may present with the pathology and, therefore, the anesthesiologist must have sound knowledge of the disease, treatment, complications, and multiorgan manifestations. It will be necessary to review the current treatment modalities for HIV as pharmacologic strategies are ever evolving with this disease process.

Congenital breast deformity reconstruction using perforator flaps.

BACKGROUND: Congenital breast deformities such as Poland syndrome, unilateral congenital hypoplasia, tuberous breast anomaly, and amastia pose a challenging plastic surgical dilemma. The majority of patients are young, healthy individuals who seek esthetic restoration of their breast deformities. Currently, both implant and autologous reconstructive techniques are used. This study focuses on our experience with congenital breast deformity patients who underwent reconstruction using a perforator flap. METHODS: From 1994 to 2005, a retrospective chart review was performed on women who underwent breast reconstruction using perforator flaps to correct congenital breast deformities and asymmetry. Patient age, breast deformity type, perforator flap type, flap volume, recipient vessels, postoperative complications, revisions, and esthetic results were determined. RESULTS: Over an 11-year period, 12 perforator flaps were performed. All cases were for unilateral breast deformities. The patients ranged from 16 to 43 years of age. Six patients had undergone previous correctional surgeries. Eight (n = 8) flaps were used for correction of Poland syndrome and its associated chest wall deformities. Four (n = 4) flaps were used for correction of unilateral breast hypoplasia. In all cases, the internal mammary vessels were the recipient vessels of choice. No flaps were lost. No vein grafts were used. All patients were discharged on the fourth postoperative day. Complications encountered included seroma, hematoma, and nipple malposition. Revisional surgery was performed in 30% of the cases. Esthetic results varied from poor to excellent. CONCLUSIONS: Perforator flaps are an acceptable choice for patients with congenital breast deformities seeking autologous breast reconstruction. Deep inferior epigastric artery (DIEP) or superficial inferior epigastric artery (SIEA) flaps are performed when adequate abdominal tissue is available; however, many young patients have inadequate abdominal tissue, thus a GAP flap can be used. Perforator flaps are a safe, reliable surgical technique. In the properly selected patient, donor-site morbidity and functional compromise are minimized, improved self-esteem is noted, postoperative pain is decreased, and excellent long-term esthetic results can be achieved.