DNA synthesis is blocked by cigarette tar-induced DNA single-strand breaks

DNA single-strand breaks are caused by aqueous extracts of cigarettetar, due to the reduction of oxygen to superoxide by tar andthe subsequent production of hydroxyl radicals. The action ofDNA metabolism enzymes on these single-strand breaks has beenstudied to probe the consequences of these lesions for DNA repair.Our results demonstrate that cigarette tar-induced nicks areblocked at the 3' terminus since they are totally incapableof activating DNA for DNA synthesis by Escherichia coli DNApolymerase I. The 3' termini of these tar-induced nicks areactivated, however, for DNA synthesis by E. coli exonucleaseIII or by the 3' phosphatase activity of T4 polynucleotide kinase.Because of the inability of tar-induced lesions to support DNAsynthesis, they probably require a multi-step process for repairin vivo. As a consequence, the overall likelihood of mutationis increased due to the possibility for error at each step ofthe repair process.     

Antioxidant property of α-asarone against noise-stress-induced changes in different regions of rat brain

Free radicals and other reactive species are considered to be an important causative factor in the development of neurodegenerative diseases. Recent reports have indicated that exposure to loud noise generates excess oxygen free radicals (OFR) in the brain. Antioxidant properties of medicinal plants are attracting more and more research in medicine, to counteract OFR and to minimize the neurodegenerative processes. The drug alpha-asarone (3, 6 and 9 mg kg(-1) body weight, i.p., for 30 days), one of the active principle components of Acorus calamus Linn., was administered intraperitoneally 1/2 h before the animals were exposed to noise-stress (100 dB for 4 h d(-1), for 30 days). We investigated whether 30 days exposure of noise can produce an oxidative stress. Further, if yes then, could alpha-asarone counteract the stress. This was verified by measuring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), levels of reduced glutathione (GSH), Vitamin C, Vitamin E, protein thiols and lipid peroxidation (LPO) in different regions of the rat brain. All the three doses of alpha-asarone had an effectively protective role by normalizing the increased SOD and LPO, decreased CAT, GPx, GSH, Vitamins C and E and protein thiols due to noise exposure. Thus, action of alpha-asarone against noise-stress may be due its antioxidant property. Our data proved that antioxidant property of alpha-asarone against noise-stress induced changes in the rat brain. Further, more clinical studies are required to investigate effectiveness of the alpha-asarone in noisy environment in human subjects.     

Valdecoxib does not impair platelet function

The platelet effects of a supratherapeutic dose of the new cyclooxygenase (COX)-2 specific inhibitor, valdecoxib (40 mg twice a day), naproxen 500 mg twice a day, diclofenac 75 mg twice a day, and placebo were compared in 62 healthy adult subjects in this 7(1/2) day single-center, randomized, placebo-controlled trial. Platelet aggregation responses (to arachidonate [AA], collagen, and adenosine diphosphate [ADP]), bleeding time, and serum thromboxane B(2) (TxB(2)) concentrations were measured at baseline and at regular intervals on days 1 and 8. Valdecoxib had no effect on platelet function. Naproxen and diclofenac significantly reduced the platelet aggregation response to AA and to a lesser extent collagen and ADP at most assessments compared with placebo. Naproxen significantly lowered serum TxB(2) levels. In contrast to standard doses of 2 nonsteroidal antiinflammatory drugs (NSAIDs), a supratherapeutic valdecoxib dosage does not impair platelet function (COX-1). Valdecoxib may be a safer analgesic option than conventional NSAIDs in patients for whom bleeding complications are a concern. (Am J Emerg Med 2002;20:275-281.     

Encapsulation of doxorubicin into thermosensitive liposomes via complexation with the transition metal manganese.

In the present study, doxorubicin was encapsulated into two thermosensitive liposome formulations which were composed of DPPC/MSPC/DSPE-PEG(2000) (90/10/4 mole ratio) or DPPC/DSPE-PEG(2000) (95/5 mole ratio). Doxorubicin loading was achieved through the use of a pH gradient or a novel procedure that involved doxorubicin complexation with manganese. Regardless of the initial drug-to-lipid ratios (D:L), the final D:L reached a maximum of 0.05 (w/w) when doxorubicin was encapsulated via a pH gradient for both thermosensitive liposome formulations. In contrast, the final maximum D:L achieved through manganese complexation was 0.2 (w/w), and this loading method did not affect temperature-induced drug release, with 85% of drug released from MSPC-containing liposomes within 10 min at 42 degrees C but <5% released over 60 min at 37 degrees C. When the thermosensitive liposomes prepared via the two different loading methods were injected into mice, similar plasma elimination profiles were observed. Cryo-transmission electron microscopy analysis indicated the presence of doxorubicin fiber bundles in liposomes loaded via pH gradient, compared to a stippled and diffuse morphology in those loaded via manganese complexation. To investigate the effect of intraliposomal pH on drug precipitate morphology, the A23187 ionophore (mediates Mn(2+)/H(+) exchange) was added to liposomes loaded with doxorubicin-manganese complex, and the stippled and diffuse appearance could be converted to one exhibiting fiber bundles after acidification of the liposome core. This suggests that the formation of doxorubicin-manganese complex is favored when the intraliposomal pH is >6.5. During the conversion to the fiber bundle morphology, no doxorubicin release was observed when A23187 was added to liposomes exhibiting a 0.05 (w/w), whereas a significant release was noted when the initial D:L was 0.2 (w/w). Following acidification of the liposomal interior and establishment of an apparent new D:L equilibrium, the measured D:L ratio was 0.05 (w/w). In conclusion, the manganese complexation loading method increased the encapsulation efficiency of doxorubicin in thermosensitive liposomes with no major impact on temperature-triggered drug release or pharmacokinetics.     

Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort

Maternal and Child Health Journal - Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment...     

Case report of Lyell's syndrome

In Lyell's syndrome a toxic skin erythema is concerned which leads to the epidermal necrolysis and desquamation. An infantile and an adult form are differed; the latter is usually induced by medicaments. Two patients with apparently medicamentously induced Lyell's syndrome are presented. The evoking medicaments were penicillin and thioacetazone. The two patients showed a severe course with an extensive affection of the body surface. The therapy with glucocorticosteroids, electrolyte substitution and local treatment of the skin lesions was successful in the two cases.     

Patients' concepts and attitudes about diabetes

ObjectiveTo evaluate the concepts and attitudes of patients and their immediate family members towards diabetes, its complications, and treatment.Research Design and MethodsA total of 654 patients with poorly controlled diabetes and 216 of their immediate family members were interviewed regarding their concept about diabetes, its complications, diet, exercise, drug therapy, and understanding about insulin.ResultsThere was lack of awareness about diabetes and its complications among the patients of diabetes. Majority of obese patients and their close family members failed to accept that they were obese. Child birth, menopause, and tubal ligation in female patients were wrongly attributed as a cause of obesity. There were major misconceptions about diet, exercise, and insulin therapy. More than 90% of study subjects had a misconception that all sweet fruits are prohibited and all bitter vegetables are beneficial. Temporary discontinuation of drug therapy was found in 189 cases. The lack of awareness and various misconceptions had no statistical relationship with the educational background of the patients.ConclusionAmong patients of poorly controlled diabetes and their close family members, there was a gross lack of knowledge of complications of diabetes, causes of obesity, treatment of diabetes, and use of insulin. Denial of obesity was commonly observed. Linking obesity with tubal ligation in female patients not only is appalling but may possibly be a hindrance to family planning program. Level of education had no bearing on these misconceptions.