Spontaneous immortalization of clinically normal colon-derived fibroblasts from a familial adenomatous polyposis patient

Normal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancer-suppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral oncogene expression (SV40 large T, HPV16/18, and E6/E7) can lead to escape from senescence, additional doublings, and entrance into crisis phase, where immortal clones emerge at low frequency. In the vast majority of cases, telomerase is reactivated and telomeres are stabilized. Here we describe the spontaneous immortalization of clinically normal fibroblasts derived from colonic stroma of a familial adenomatous polyposis (FAP) patient. The preimmortal (C26C) and the spontaneously immortalized derivative (C26Ci) cells are heterozygous for a characterized germline mutation in exon 15 of the adenomatous polyposis coli gene. Immortalization was accompanied by spontaneous reactivation of endogenous telomerase and establishment of telomeres at presenescent lengths. Normal checkpoint behavior is retained and a diploid karyotype is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, and will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention.     

Comparative evaluation of Midazolam and Propofol as intravenous sedative agents in the management of unco-operative children

Dental treatment of very young children (toddlers) as well as children with highly negative behaviour is known to be difficult. Management of these children requires special skill and at times the support of pharmacological means. A study was planned and carried out to evaluate and compare the efficacy and safety of Propofol and Midazolam as Intravenous sedative agents in the management of uncooperative children belonging to age group 2-5 years, ASA I Category and Frankl's behaviour rating 1 and 2. The results showed both agents to be effective sedative agents, for short pedodontic procedures with minimal side effects.     

Antiulcer activity of levcromakalim and nicorandil in albino rats: a comparative study

The objective of the present study was to investigate and compare the antiulcer effect of potassium channel openers, nicorandil and levcromakalim in the models of ulcer induced by pylorus ligation, aspirin and water immersion plus restraint stress in albino rats. Levcromakalim (250 microg/kg) and nicorandil (10 mg/kg) were administered intraduodenally immediately after pylorus ligation. Ulcer index was determined and gastric juice was subjected to analysis of total acid output (TAO) and pH. In aspirin-induced gastric ulcer model, the drugs were administered orally 30 min prior to noxious challenge, and in water immersion restraint stress model, the drugs were administered orally and ulcer index was determined. A significant reduction in ulcer index was observed after treatment with both potassium channel openers in all the gastric ulcer models. In pylorus-ligated rats, a significant decrease in TAO was noted. The conclusion is that potassium channel openers possess antiulcer activity. Antiulcer activity of levcromakalim is better than nicorandil but comparable to that of cimetidine. The antiulcer action of potassium channel openers is mediated partially by a decrease in gastric acid secretion, increase in gastric mucosal resistance and improvement in gastric mucosal blood flow.     

Antibody-targeted chemotherapy with immunoconjugates of calicheamicin

Targeted delivery of cytotoxic agents to tumours is believed to improve both their anti-tumour efficacy and their safety. Antibodies specific for tumour-associated antigens have been used to deliver cytotoxic agents to tumour cells. Calicheamicin is a potent cytotoxic agent that causes double-strand DNA breaks, resulting in cell death. When conjugated to monoclonal antibodies specific for tumour-associated antigens, calicheamicin exerts strong antigen-specific anti-tumour effects against human tumour xenografts in preclinical models. Antibody-targeted chemotherapy with immunoconjugates of calicheamicin, exemplified by gemtuzumab ozogamicin (Mylotarg), is a clinically validated therapeutic strategy for the treatment of human cancer.     

Management of vitreous haemorrhage

Vitreous hemorrhage is one of the most common differential diagnoses for sudden painless decrease in vision. Often, it is caused by retinal vascular disorders secondary to common systemic ailments such as diabetes mellitus, systemic hypertension and haematological abnormalities. Sometimes it may be the beginning of a retinal tear and consequent retinal detachment that can be vision threatening if not operated early. This paper lays out practical guidelines for a tailored approach needed to arrive at the aetiology of vitreous haemorrhage so that appropriate, timely treatment can be planned.     

Dentigerous cyst in the maxillary sinus: a rare cause of nasolacrimal obstruction

The main types of maxillary cysts are antral mucoceles, retention cysts, pseudocysts, dentigerous cysts and keratocysts. Despite the theoretical possibility of maxillary sinus cysts leading to nasolacrimal duct obstruction, only two cases have been reported in the literature so far. The present authors report this rare presentation of a dentigerous cyst with a tooth in the roof of the maxillary sinus, which led to nasolacrimal duct obstruction.