Determination of extent of formaldehyde-induced crosslinking in hard gelatin capsules by near-infrared spectrophotometry

PURPOSE: To predict the degree of crosslinking from formaldehyde-stressed hard gelatin capsules (HGCs) using near-infrared spectrophotometry (NIR). METHODS: HGCs were exposed to a 150 ppb atmosphere of formaldehyde for 2.25, 4.60, 9.42, 16.0 and 24.0 hours. The capsules were filled with fresh amoxicillin, placed in a 90 degrees conical reflector cone, and scanned in a NIR spectrophotometer. Principal component regression (PCR) was employed to analyze the spectra of the intact capsules. Dissolution profiles were then obtained for each experimental group. RESULTS: The dissolution of amoxicillin from the capsules at pH 1.2 was found to decrease with increasing time of exposure to the formaldehyde atmosphere. A set of principal components (PCs) was formed by a linear combination of the absorbance values at each wavelength scanned. A good correlation was established (r2 = 0.963) when PC values from the NIR spectra of the HGCs were regressed against percentage of amoxicillin dissolved at 45 minutes, at pH 1.2. Water content of the capsules was found to be the largest determinant in the variation between HGC spectra at each exposure time. CONCLUSIONS: NIR spectrophotometry, combined with PCR, was successful at not only predicting dissolution of HGCs exposed to formaldehyde, but also at determining which wavelengths contributed most to spectral variation of these stressed HGCs.     

Correlates of victimization in Chinese children's peer groups.

This study reports a cross-sectional investigation of the behavioral and academic correlates of victimization in Chinese children's peer groups. The participants were 296 children (161 boys and 135 girls; mean age?=?11.5 years) from Tianjin, China. Multi-informant assessments (peer nominations, teacher ratings, and self-reports) of peer victimization, aggression, submissiveness-withdrawal, assertiveness-prosociability, and academic functioning were obtained. Structural equation models indicated that peer victimization was associated with poor academic functioning, submissive-withdrawn behavior, aggression, and low levels of assertive-prosocial behavior. These findings suggest that there is considerable similarity in the social processes underlying peer group victimization across Chinese and Western cultural settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Population dynamics of the deer mouse (Peromyscus maniculatus) and Sin Nombre virus, California Channel Islands

Alteration of the wild-type (wt) p53 gene by mutation, deletion or re-arrangement is a major factor in the development of human colon cancer. Recent studies have demonstrated that p53 might be an essential component of the apoptotic pathway triggered by DNA-damaging stimuli such as chemotherapeutic agents and ionizing radiation. We examined the anti-tumor effects of adenovirus-mediated wt-p53 gene transfer in combination with a chemotherapeutic drug on the human colon cancer cell line WiDr, which is homozygous for a mutation in the p53 gene. Treatment with the chemotherapeutic drug cisplatin following infection with a replication-deficient, recombinant adenoviral vector expressing wt-p53 (termed AdCMVp53) significantly suppressed the growth of WiDr cells compared to single treatments alone. To evaluate the in vivo efficacy of AdCMVp53 and cisplatin given sequentially, WiDr cells were inoculated s.c. in nu/nu mice. After 3 days, AdCMVp53 was injected s.c. into the area where tumor cells were implanted, followed by i.p. administration of cisplatin. Analysis of initial growth inhibition at 21 days demonstrated a profound therapeutic cooperativity, though administration of either AdCMVp53 or cisplatin alone was followed only by a slowing of growth. Our results suggest that gene therapy using wt-p53-expressing adenovirus in combination with a chemotherapeutic DNA-damaging drug could be a useful strategy for treating human colon cancer.     

Being a stroke patient: a review of the literature

The purpose of this paper is to review the research literature on the patient's experience of stroke. Four qualitative studies on how patients experience stroke were identified. The findings of these studies show that the stroke patient often has clear goals for himself in relation to functional abilities, against which he measures all success and forward progress in his rehabilitation. Even though the stroke patient accepts a lower level of functional ability, he is not willing to accept the rehabilitation professionals' prediction of his ultimate functional level if it is lower than his own goal. Furthermore, stroke patients see recovery as a return to the existence they had lived before the stroke, which is different from the health care providers' view. To the health care provider, recovery is measured in terms of isolated and discrete return of movement, whereas in the eyes of the patients, recovery is a return to previously valued activities. Further, studies on psychosocial function after stroke were reviewed. Recent studies show that the psychological impact of the stroke experience is immense and that stroke patients experience stress on a variety of levels. Also, depression exists in a large portion of the stroke population. The impact of stroke also influences the patient's social existence, as studies have shown that stroke patients do manifest diminished social function. However, the reviewed studies are not without limitations. Further studies, with a qualitative design, are needed to throw light on the patient's experience of being ill with stroke, and the process of his recovery.     

Selective activation by bryostatin-1 demonstrates unique roles for PKC epsilon in neurite extension and tau phosphorylation

The purpose of this study was to contrast the discharge patterns of the same motor units during movements and during isometric contractions that were produced with comparable torque-time characteristics. Subjects performed elbow flexion and extension movements with predetermined acceleration characteristics. The average acceleration and deceleration profiles for the movements were reproduced in the isometric setting by presenting the kinematic profiles as templates for torque production. Trained subjects were able to match the first agonist (AG1) and antagonist (ANT) electromyographic (EMG) bursts, but tended to produce a smaller second agonist burst (AG2) in the isometric contraction. Twenty-five motor units from triceps brachii were studied. The same motor units (with one exception) were recruited and subsequently discharged in a similar fashion in both the isometric and movement tasks in the AG1 and ANT EMG bursts, with fewer motor unit discharges in the AG2 burst in the isometric contraction. The central control mechanisms appear to be the same for the acceleration phase of movement and isometric contraction, but differ during the deceleration phase.     

What is the relationship between osteoarthritis and ageing?

The relationship between osteoarthritis and ageing raises important questions about what exactly defines 'normal' ageing and whether the pathogenesis of osteoarthritis shares common pathways with other age-associated dysfunctions, or whether osteoarthritis is a time-dependent disorder distinct from normal ageing with a separate causative mechanism at work. Theories of ageing now emphasize the stochastic nature of the ageing process, that is the role played by accumulation of essentially random cell and tissue damage, such as somatic mutations, oxidative damage and the formation of aberrant proteins. The role of genetic factors in determining longevity and predisposition to age-associated diseases is probably in programming the efficiency of somatic maintenance functions and in influencing the development of a durable soma. Gene-environment interactions, for example through lifestyle, can also be important. Many of the risk factors and mechanisms that are thought to contribute to osteoarthritis can be accommodated within this framework.     

Immune parameters in athletes before and after strenuous exercise

Secretory IgA levels were studied in nationally ranked Nordic skiers before and after the national cross-country races held in February 1981. Comparing the skiers with age-matched controls, there was significantly lower level of salivary IgA before the race. Concentrations of IgA decreased further following the competition (50 kn for males; 20 km for females) to very low levels. There also were a significant increase in the percentage of B lymphocytes and a decrease in the null population (non-T, non-B) in the athletes after the race compared with the controls. The mechanism responsible for these changes is unknown, but the low salivary IgA levels may result from depletion of nasal fluid and/or malfunction of the mucosal plasma cells due to a decrease temperature in the mucous membranes. We speculated that a temporary antibody deficiency on the mucosal surface might lead to a susceptibility to acquiring viral and bacterial infections, especially during the interval immediately following strenuous exercise.     

Laminin directs growth cone navigation via two temporally and functionally distinct calcium signals

During development, growth cones navigate to their targets via numerous interactions with molecular guidance cues, yet the mechanisms of how growth cones translate guidance information into navigational decisions are poorly understood. We have examined the role of intracellular Ca2+ in laminin (LN)-mediated growth cone navigation in vitro, using chick dorsal root ganglion neurons. Subsequent to contacting LN-coated beads with filopodia, growth cones displayed a series of stereotypic changes in behavior, including turning toward LN-coated beads and a phase of increased rates of outgrowth after a pause at LN-coated beads. A pharmacological approach indicated that LN-mediated growth cone turning required an influx of extracellular Ca2+, likely in filopodia with LN contact, and activation of calmodulin (CaM). Surprisingly, fluorescent Ca2+ imaging revealed no LN-induced rise in intracellular Ca2+ in filopodia attached to their parent growth cone. However, isolation of filopodia by laser-assisted transection unmasked a rapid, LN-specific rise in intracellular Ca2+ (+73 +/- 11 nM). Additionally, a second, sustained rise in intracellular Ca2+ (+62 +/- 8 nM) occurred in growth cones, with a distinct delay 28 +/- 3 min after growth cone filopodia contacted LN-coated beads. This delayed, sustained Ca2+ signal paralleled the phase of increased rates of outgrowth, and both events were sensitive to the inhibition of Ca2+/CaM-dependent protein kinase II (CaM-kinase II) with 2 microM KN-62. We propose that LN-mediated growth cone guidance can be attributed, in part, to two temporally and functionally distinct Ca2+ signals linked by a signaling cascade composed of CaM and CaM-kinase II.     

Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy

Hypertension is a major cause of heart failure, evolving from left ventricular hypertrophy to systolic and diastolic dysfunction. Although effective heart failure therapy has been associated with a lowering or no change in systemic arterial blood pressure in long-term follow-up, this study describes the symptomatic, clinical, and left ventricular functional response of a subgroup of heart failure patients with a prior history of hypertension who demonstrated a paradoxical hypertensive response despite high-dose vasodilator therapy. We prospectively identified 45 patients with a past history of hypertension who had become normotensive with symptomatic heart failure. Of these 45 heart failure patients, 12 became hypertensive while receiving therapy in follow-up, with systolic blood pressure > or = 140 mm Hg (Group A). The remaining 33 patients did not have a hypertensive response to therapy (Group B). In the 12 Group A patients, 60+/-10 years old, with symptomatic heart failure for 6.3+/-4.3 years, vasodilator therapy was intensified in the 2.0+/-0.5 years of follow-up, achieving final doses of enalapril 78+/-19 mg and isosorbide dinitrate 293 +/-106 mg per day. New York Heart Association classification improved from 2.9+/-0.8 to 1.3+/-0.5 (P < or = .0001), with a reduction in heart-failure-related hospitalizations. Left ventricular ejection fraction increased from 17+/-6% to 40+/-10% (P < .0001). Follow-up blood pressure at 1 to 3 months was unchanged. However, both systolic and diastolic blood pressure increased at final follow-up, rising from 116+/-14 to 154+/-13 mm Hg (P = .0001) and from 71+/-9 to 85+/-14 mm Hg (P = .004), respectively. Renal function remained unchanged. Although both groups had similar clinical responses, there were more blacks and women in the hypertensive Group A. Effectively, 12 of 45 (27%) heart failure patients with an antecedent history of hypertension demonstrated a paradoxical hypertensive response to vasodilator therapy. The recurrence of hypertension in a significant portion of patients successfully treated for heart failure has important clinical implications.     

Inactivation of O6-alkylguanine-DNA alkyltransferase. 1. Novel O6-(hetarylmethyl)guanines having basic rings in the side chain

A number of novel guanine derivatives containing heterocyclic moieties at the O6-position have been synthesized using a purine quaternary salt which reacts with alkoxides under mild conditions. Initially O6-substituents were investigated in which the benzene ring of the known agent, O6-benzylguanine, was replaced by unsubstituted heterocyclic rings. The ability of these agents to inactivate the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase), both as pure recombinant protein and in the human lymphoblastoid cell line Raji, has been compared with that of O6-benzylguanine. The present paper focuses on O6-substituents with basic rings, and under standard conditions several of them proved more effective than benzyl for inactivation of both recombinant and Raji ATase. Among the pyridine derivatives, the 2-picolyl compound 7 is not very active in contrast to the 3- and 4-picolyl compounds, and this influenced our choice of isomers of other basic ring systems for study. Since halogen substitution in the thiophene ring considerably increased the activity (17 versus 6), similar modifications in the pyridine series were examined. The more polar O6-substituents in this study are on the whole compatible with the stereochemical requirements of the ATase protein, and their pharmacological properties may be valuable in subsequent in vivo investigations, particularly the thenyl (6), 5-thiazolylmethyl (12), 5-bromothenyl (17), and 2-chloro-4-picolyl (21) derivatives.