Selective and validated spectrophotometric methods for the determination of nicorandil in pharmaceutical formulations

Two simple and sensitive validated spectrophotometric methods have been described for the assay of nicorandil in drug formulations. Method A is based on the reaction of the drug with phloroglucinol-sulfanilic acid reagent in sulfuric acid medium to give yellow-colored product, which absorbs maximally at 425 nm. Method B uses the oxidative coupling of 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) with DL- 3,4 - dihydroxyphenylalanine (DL-dopa) in the presence of nicorandil as oxidant in sulfuric acid medium to form an intensely colored product having maximum absorbance at 530 nm. Beer's law is obeyed in the concentration range 2.5 to 50.0 and 1.0 to 15.0 microg mL(-1) with methods A and B, respectively. Both methods have been successfully applied for the analysis of drug in pharmaceutical formulations. The reliability and the performance of the proposed methods are established by point and interval hypothesis and through recovery studies. The experimental true bias of all samples is smaller than +/-2%.     

Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D

Vitamin D requirements are thought to vary with age, but there is little comparative evidence for this. One goal in establishing a vitamin D requirement is to avoid secondary hyperparathyroidism. We studied 1741 euthyroid, thyroid clinic outpatients without evidence of calcium abnormalities, ranging in age from 19 to 97 yr, whose serum and urine had been analyzed for calcium, vitamin D, and parathyroid status. We found no effect of age on the 25-hydroxyvitamin D [25(OH)D] concentration associated with specific vitamin D intakes, and there was no relationship between 25(OH)D and 1,25hydroxyvitamin D [1,25(OH)2D]. In every age group, serum 1,25(OH)2D declined with increasing creatinine (P < 0.001). What changed with age included creatinine, which correlated with 25(OH)D (r = 0.146, P < 0.001) only in the youngest age group (19-50 yr) but not in the older age groups (P > 0.1). Creatinine did not correlate with PTH in the youngest age group, but the relationship became significant as age increased (e.g. for the elderly, r = 0.365, P < 0.001). Linear regression of log PTH vs. log 25(OH)D agreed with the natural shape of the relationship observed with scatterplot smoothing, and this showed no plateau in PTH as 25(OH)D increased. We compared PTH concentrations among age groups, based on 20 nmol/liter increments in 25(OH)D. Mean PTH in adults older than 70 yr was consistently higher than in adults younger than 50 yr (P < 0.05 by ANOVA and Dunnett's t test). PTH levels of the elderly who had 25(OH)D concentrations greater than 100 nmol/liter matched PTH of younger adults having 25(OH)D concentrations near 70 nmol/liter. This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function.     

Effects of simvastatin on bone regeneration in the mandibles of ovariectomized rats and on blood cholesterol levels

The purpose of this study was to evaluate the effects of simvastatin on guided bone regeneration in the mandibles of ovariectomized rats, and to observe their blood cholesterol levels. Seventy female rats were divided into two groups: control and treated, both groups containing normal and ovariectomized rats. A month after ovariectomy a bone defect was created in the mandible, and was covered by a polytetrafluoroethylene membrane. The treated groups received simvastatin orally for 15 or 30 days. The rats were sacrificed 15, 30 or 60 days after surgery, at which time a blood sample was extracted for blood cholesterol level analysis and the mandible was extracted for densitometric, histological and morphometric analysis. All specimens underwent analysis of variance. The ovariectomized animals had higher cholesterol levels than the treated normal animals, and no significant difference was found between the different treatment periods and the sacrifice times. The densitometric, histological and morphometric analysis showed that the treated ovariectomized animals developed more new bone than the control ovariectomized rats, but no significant difference was observed between the treatment periods. It can be concluded that the deficiency of estrogen increased the level of blood cholesterol and that the simvastatin aided new bone formation in the ovariectomized animals.     

Characteristics of mixed diagnostic radiology-radiation oncology practices

OBJECTIVE: Our objectives were to describe the characteristics of "mixed practices"-that is, practices performing both diagnostic radiology and radiation oncology services-and to compare mixed practices with multiradiologist diagnostic radiology-only practices. MATERIALS AND METHODS: In 1999, the American College of Radiology surveyed 970 practices by mail, using a 65-item questionnaire. A response rate of 66% was achieved. Responses were weighted such that they were representative of all the radiology practices in the United States. The estimates cited in this article were primarily drawn from this 1999 survey. RESULTS: Mixed practices were nearly evenly divided between large (area population, > or = 1 million) and small metropolitan areas (area population, from 50,000 to 1 million). We found that 63% of mixed practices were nonacademic private practices; 27% were academic. Approximately 50% contained 15 or more members. Mixed practices were predominantly owned by members of the practice and predominantly served both hospitals and nonhospital settings. At least 90% of mixed practices performed mammography, imaging-guided breast biopsy, sonography, and nuclear medicine.We found that compared with multiradiologist diagnostic radiology-only practices, mixed practices were larger and were more likely to be academic, to serve both hospital and nonhospital settings, and to perform interventional and nuclear medicine procedures. CONCLUSION: The characteristics of a mixed practice differ from those of a multiradiologist diagnostic radiology-only practice.     

A phase I study of pegylated liposomal doxorubicin hydrochloride (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small-cell lung cancer

The purpose of this study was to determine the recommended phase II dose of liposomal doxorubicin (Caelyx ; Doxil in the United States) in combination with cyclophosphamide and vincristine for previously treated patients with good performance status with relapsed or refractory small-cell lung cancer. Twenty-one eligible patients were enrolled between November 1999 and September 2001 and received liposomal doxorubicin 25-40 mg/m2, cyclophosphamide 750-1000 mg/m2, and vincristine 1.2 mg/m2 intravenously (I.V.) every 21 days. At doses of liposomal doxorubicin 40 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V., 1 of 6 patients had dose-limiting neutropenia and fever in cycle 2 and 2 of 6 developed grade 3 hand-foot syndrome during cycle 3. Therefore, the recommended phase II doses are liposomal doxorubicin 35 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V. every 21 days. Antitumor activity was seen at all dose levels. This combination is well tolerated and has evidence of antitumor activity. A phase II evaluation is ongoing.     

Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain

Substance P exerts its various biochemical effects mainly via interactions through neurokinin-1 receptors (NK1). Recently, the NK1 receptor has attracted considerable interest for its possible role in a variety of psychiatric disorders including depression and anxiety. However, little is known regarding the anatomical distribution of NK1 in the human central nervous system (CNS). Riboprobe in situ hybridization, quantitative PCR and in vitro autoradiography were performed. Highest NK1 mRNA levels were localized in the locus coeruleus and ventral striatum, while moderate hybridization signals were observed in the cerebral cortex (most abundant in the visual cortex), hippocampus and different amygdaloid nuclei. Very low levels of the NK1 mRNA were detected in the cerebellum and thalamus. In view of the existence of a long and short isoform of the NK1 receptor, it was of interest to assess whether there was a differential distribution of the two splice variants in the human CNS and peripheral tissues. A quantitative TaqMan PCR analysis showed that the long NK1 isoform was the most prevalent throughout the human brain, while in peripheral tissues the truncated form was the most represented. 3H-Substance P autoradiography revealed a good correlation between receptor binding sites and NK1 mRNA expression throughout the brain, with the highest levels of binding in the locus coeruleus. These results provide the anatomical evidence that the NK1 receptors have a strong association with neuronal systems relevant to mood regulation and stress in the human brain, but do not suggest a region-specific role of the two isoforms in the CNS.     

A study of pediatric blood lead levels in a lead mining area in South Africa

This study aimed to determine the blood lead distributions among young children in the lead mining town of Aggeneys in South Africa's Northern Cape Province, and in the comparison community of Pella, about 40 Km away. A further objective of the study was to explore factors associated with elevated blood lead levels. Children aged between 6 and 10 years (average age, 8 years) were studied, 86 from Aggeneys and 68 from Pella. The results showed that blood lead levels among the children of Aggeneys averaged around 16 microg/dL, while in Pella the mean blood lead level equaled 13 microg/dL. Overall, children with raised blood lead levels performed less well at school relative to other children. Within Aggeneys, fathers of "high" lead children tended to shower at work rather than at home, which may have been insufficient to prevent lead from being transported into the home. In conclusion, more stringent environmental control measures are needed, as well as stricter personal hygiene measures, to prevent childhood lead exposure in the mining community.     

Adiposity indices and their relationship with some risk factors of coronary heart disease in middle-aged Cambridge men and women

The relationship between five anthropometric measures (body mass index, waist to hip ratio, conicity index, waist circumference and waist to height ratio) and seven cardiovascular risk factors (total cholesterol, high and low density lipoprotein cholesterol, ratio of total cholesterol to high density lipoprotein and ratio of high density lipoprotein to low density lipoprotein cholesterol, systolic and diastolic blood pressure), were studied in 165 men and 202 women aged between 40 and 69 years living in an urban area of Cambridge, UK. Inter-correlations between the anthropometric measures varied between 0.34 and 0.92 and were generally higher in males than females. Tests of homogeneity of the five correlation coefficients for each risk factor revealed no significant heterogeneity for males, but significant differences for high density lipoprotein and ratio of total cholesterol to high density lipoprotein were found in females. Waist to hip ratio showed the highest correlations with the risk factors in women (3 out of 7), but no consistent pattern was found for males. Males had significantly lower cholesterol, low density lipoprotein cholesterol levels than females for any given waist to hip ratio and conicity index, waist circumference and waist to height ratio. In addition, men also had lower total cholesterol to high density lipoprotein cholesterol and high density lipoprotein cholesterol to low density lipoprotein cholesterol levels for waist to hip ratio or conicity index.