Cell survival characteristics of a human colon adenocarcinoma cell line after photodynamic treatment: a comparison of Photofrin II and TPPS

A comparison has been made of the in vitro light-activated drug cytotoxicities of two different porphyrin compounds, Photofrin II and TPPS4. An early passage human colon adenocarcinoma cell line, WiDr, has been exposed to either drug for 24 h, the excess drug washed from the cells and the cells irradiated with light using quartz-tungsten-halogen lamps. Neither light nor drug alone under the experimental conditions employed was toxic to WiDr cells. Together, considerable cytotoxicity could be seen and the shapes of the cell survival curves following exposure to either drug then irradiation with light, were similar. For equal amounts of drug in the medium, Photofrin II was a more efficient photosensitizer of WiDr cells than TPPS4, and differences in cellular uptake could only partly explain this. When the experimental procedure was changed by reducing the temperature of irradiation, a reduction in photosensitizing efficiency could be demonstrated. This was more pronounced for Photofrin II, and was seen as a change in the slope of the final portion of the survival curve; and as a change in the shoulder for TPPS4. Two different batches of the two drugs were compared and shown to give slightly different results for Photofrin II (change in shoulder) but not to differ for TPPS4.     

Noncortical origins of the spinal motor evoked potential in rats

Motor evoked potentials (MEPs) were recorded from the spinal cord, sciatic nerve, or both during transcortical electrical stimulation in the rat. Four peaks could be consistently identified in the spinal MEP. The latency and amplitude of the peaks varied differentially with intensity and polarity of stimulation. Conduction velocity for Peak 1 of the MEP was 43 m/sec. Bilateral sciatic nerve MEPs were present after unilateral cortical stimulation. The spinal MEP was elicited by stimulation of areas outside the motor cortex, and the response persisted during subcortical stimulation and after motor cortex ablation. We present evidence suggesting that components of the spinal MEP in rats arise from pathways outside the motor cortex.     

Improved neuropsychological outcome in children with brain tumors diagnosed during infancy and treated without cranial irradiation.

Neuropsychological outcome of 28 patients with brain tumors diagnosed before the age of 36 months (mean, 19 months) was assessed using a comprehensive battery of tests. Elapsed time between diagnosis and testing averaged 6.2 years. Half the patients had received cranial radiation therapy and surgery, with and without chemotherapy, whereas the rest had received only surgery, with or without chemotherapy. Groups were comparable with respect to tumor diagnosis and location, age at diagnosis, race, and sex. Intellectual functioning was significantly lower in children whose treatment included cranial irradiation than in those treated without cranial irradiation, and this effect was more pronounced in nonverbal than in verbal intellectual abilities. Mean scores for the radiation group were lower than for the no-radiation group in all areas assessed and were significantly below age-based normative means in five of the eight cognitive areas: intellectual, memory, attention, motor, and visual-spatial skills. Mean scores for children in the no-radiation group were generally within the average range in all cognitive areas except visual-spatial skills, which were significantly below age-based normative means. Endocrine deficiencies and growth retardation were much more prevalent in patients treated with cranial irradiation. Because the immature brain is susceptible to treatment-related pathologic changes, infants are at greater risk than older children for significant, long-term neuropsychological, endocrine, and growth sequelae. In children treated without cranial irradiation, morbidity was minimized without an increased rate of mortality.     

Differences in a K current in schwann cells from normal and neurofibromatosis-infected damselfish

Patch clamp techniques were used to study whole cell ionic currents in Schwann cells (SC) from a tropical marine fish, the bicolor damselfish, Pomacentrus partitus. The bicolor damselfish is affected by a disease termed damselfish neurofibromatosis (DNF), being developed as an animal model of neurofibromatosis-type 1 (NF1) in humans. NF1 affects SC, fibroblasts, and perineurial cells. The sole depolarization-activated ionic current present in cultured SC from normal fish peripheral nerve and from neurofibromas of fish with induced or spontaneously occurring DNF was an inactivating K⁺ current (K current), with a strong dependence on the Nernst potential for K⁺. This K current activated at depolarizations to -40 mV and above and inactivated during a maintained test pulse (0.2-1 s), but inactivation was significantly greater in tumored SC. Both currents were inhibited by 4-aminopyridine (K_d ? 1 mM) and by dendrotoxin (15 μM) but were insensitive to extracellular tetraethyammonium (≤ 150 mM), indicating that the whole cell currents were similar pharmacologically. The currents could be distinguished on the basis of their sensitivity to depolarized holding potential, with normal cells less sensitive. Half-inactivation of the current was -32 mV in normal cells and -38 mV in tumored cells. Inactivation curves constructed from the average normalized current for many SC were significantly different in normal and tumored cells. When the depolarized holding potential was maintained between test depolarizations, greater voltage-dependent inactivation in tumored cells was apparent. Normal cells maintained an average of 36% of peak current at a holding voltage of ?40 mV, while in tumored cells this average was 12%, a significant difference. © 1994 Wiley-Liss, Inc.     

Development of a fetal circadian rhythm after disruption of the maternal circadian system

The role of maternal circadian rhythms in the development of the fetal circadian system was investigated in the rat. Pregnant females were subjected to procedures known to disrupt circadian function, ablation of the maternal suprachiasmatic nuclei (SCN) or housing in constant illumination, on gestational day 10. Circadian function was assessed in fetuses at gestational day 22 by analysis of glucose utilization in hypothalamic slices in vitro using the 2-deoxyglucose method. Fetuses from control females exhibit a robust rhythm in glucose utilization in the SCN. In contrast, the SCN of fetuses from females with SCN lesions, or housed in constant illumination, show no significant day-night difference in glucose utilization. Analysis of individual brains indicates, however, that this apparent disruption in the development of circadian rhythmicity in metabolism in the fetal SCN is due to a desynchronization of individual fetuses resulting from the loss of maternal entraining influences. Thus, the fetal SCN is capable of developing a circadian rhythm in glucose utilization independent of the maternal circadian system.     

Tics moderate treatment outcome with sertraline but not cognitive-behavior therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: The presence of a comorbid tic disorder may predict a poorer outcome in the acute treatment of pediatric obsessive-compulsive disorder (OCD). METHODS: Using data from the National Institute of Mental Health (NIMH)-funded Pediatric OCD Treatment Study (POTS) that compared cognitive-behavior therapy (CBT), medical management with sertraline (SER), and the combination of CBT and SER (COMB), to pill placebo (PBO) in children and adolescents with OCD, we asked whether the presence of a comorbid tic disorder influenced symptom reduction on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) after 12 weeks of treatment. RESULTS: Fifteen percent (17 of 112) of patients exhibited a comorbid tic disorder. In patients without tics, results replicated previously published intent-to-treat outcomes: COMB > CBT > SER > PBO. In patients with a comorbid tic disorder, SER did not differ from PBO, while COMB remained superior to CBT and CBT remained superior to PBO. CONCLUSIONS: In contrast to CBT outcomes, which are not differentially impacted, tic disorders appear to adversely impact the outcome of medication management of pediatric OCD. Children and adolescents with obsessive-compulsive disorder and a comorbid tic disorder should begin treatment with cognitive-behavior therapy alone or the combination of cognitive-behavior therapy plus a serotonin reuptake inhibitor.     

Protein carbonyls are acutely elevated following single set anaerobic exercise in resistance trained men

The purpose of this investigation was to determine if a single set of strenuous squat exercise would result in an acute oxidative stress, as demonstrated previously by a single sprint. Thirteen resistance trained men performed one set of 15 repetitions of barbell squats using 70% of one repetition maximum and a 30 s maximal cycle sprint on two different occasions. The total work performed was calculated for each exercise bout. Heart rate, perceived exertion, blood lactate, protein carbonyls, 8-hydroxydeoxyguanosine, and malondialdehyde were measured before and within 1 min following exercise. No differences were noted between the squat and sprint tests for total work, heart rate or perceived exertion. An exercise test by time interaction was evident for blood lactate with values greater following sprinting compared to squatting (P = 0.0005). Postexercise protein carbonyls were not different between exercise tests but were elevated above rest (P = 0.04) by 111% and 74% following sprinting and squatting, respectively, while 8-hydroxydeoxyguanosine and malondialdehyde were relatively unaffected by either exercise test. These data indicate that a single bout of strenuous squatting and sprinting performed by resistance trained men results in elevated protein carbonyls, while having little impact on 8-hydroxydeoxyguanosine or malondialdehyde during the immediate postexercise period.     

Natural history of morbid obesity without surgical intervention.

BACKGROUND: To study the mortality among morbidly obese patients qualifying for bariatric surgery. Mortality from bariatric surgery for morbid obesity has been widely reported; however, little is known about the mortality in morbidly obese patients who defer surgery. METHODS: Consecutive patients evaluated for bariatric surgery with an initial encounter between 1997 and 2004 were identified. The Social Security Death Index and office records were used to identify mortality through 2006. We conducted telephone interviews to determine whether the 305 patients who did not undergo bariatric surgery at our institution had undergone the surgery elsewhere. Using Cox proportional hazards models, we compared the mortality in patients undergoing surgery with that of those who did not. To evaluate bias resulting from missing data, we conducted analyses assuming that all patients with missing data had (1) undergone surgery and (2) not undergone surgery. RESULTS: A total of 908 patients underwent bariatric surgery (880 patients at our institution and 28 patients elsewhere). A total of 112 patients did not undergo surgery. Data regarding surgery on 165 patients could not be obtained. The mortality in those patients who did not undergo surgery was 14.3% compared with 2.9% for those who did undergo surgery. Adjusting for age, gender, and body mass index, patients who had undergone surgery had an 82% reduction in mortality (hazard ratio 0.18, 95% confidence interval 0.09-0.35, P <.0001). Sensitivity analysis, assuming that all patients with missing data received surgery resulted in an 85% mortality reduction (P <.001) and assuming that patients did not receive surgery resulted in a 50% mortality reduction (P = .04). CONCLUSIONS: Mortality among morbidly obese patients without surgery was 14.3% during the study period. Surgical intervention offered a 50%-85% mortality reduction benefit.