High dose vitamin A supplementation in the course of pneumonia in Vietnamese children

We carried out a randomized, placebo-controlled, double-blinded trial to evaluate the effect on morbidity of high dose oral vitamin A, given on hospital admission to 592 children aged 1–59 months with moderate and severe pneumonia. Severely underweight children were not included, but 45% were moderately underweight. The vitamin A and placebo groups were comparable in baseline characteristics. Four patients died. Among all of the surviving children, no differences were found regarding mean time for normalization of fever, respiratory rate and time of hospitalization. Stratification for moderate malnutrition, degree of pneumonia, age and sex revealed moderately malnourished vitamin A-supplemented children to have a shorter time of hospitalization ( p = 0. 04), due to an effect in females aged > 12 months ( p = 0. 02) and females with very severe pneumonia ( p = 0. 048). This study indicates that, in developing countries like Vietnam, supplementation with vitamin A in children with pneumonia could shorten the recovery rate in the ones that are undernourished, especially females > 1 y old.     

The association of expression and gene polymorphism of the thymidylate synthase gene with 5-fluoro-5'-deoxyuridine sensitivity in gastric cancer cell lines

Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU), and the TS expression level of cancer tissues is a potential predictor of the response to 5-FU-based chemotherapy. The TS gene has a polymorphic tandem-repeat sequence, which is associated with its protein expression. Therefore, the TS polymorphism may also be a predictor of the response to 5-FU-based chemotherapy. In this study, we analyzed the TS genotype, TS protein level, and sensitivity to 5-fluoro-5'-deoxyuridine (5'-dFUrd) in 10 human gastric cancer cell lines. TS genotype was classified into 2R-homozygote (2R/2R, n=3), 3R-homozygote (3R/3R, n=5), and 2R/3R-heterozygote (2R/3R, n=2). The cell lines with 3R/3R showed a significantly higher IC50 value compared to those with 2R/2R or 2R/3R genotype. There was no relationship between TS protein level and 5'-dFUrd sensitivity. However, a statistically significant relationship was revealed between them when the subgroup with the genotypes of 2R/2R or 2R/3R was considered (r=0.815, p<0.05). In this subgroup, the cell lines with higher TS protein showed higher IC50 value for 5'-dFUrd, indicating less sensitivity to 5'-dFUrd. An identical relationship between the TS protein level and IC50 was also observed in the subgroup with 3R/3R genotype, although it did not reach statistical significance (r=0.745, p=0.09). These results suggest that the TS gene polymorphism and TS protein level may be independent predictors for 5-FU-based chemotherapy.     

Characteristics of the communication in individuals with fragile X syndrome

The aim of this study was to make a characterization of the communication in a group with fragile X syndrome (FXS), based on normal development scale. The sample has 10 boys, between 6 and 13 years and with FXS. All of them were submitted to language evaluation. The most part of them had the communication in linguistic form (80%), until 3 years old. It was considered that the data confirmed the significant delay in the acquisition and development of the communication, being necessary an early and specialized intervention.     

Increased serum thymidine kinase activity in acute sarcoidosis

This is the first case report of acute sarcoidosis with increased serum thymidine kinase (TK) activity. A 43-year-old male presented fever, swelling of parotid glands, lymphadenopathy, and peripheral neuropathy. Sarcoidosis was pathologically diagnosed by lung and parotid gland biopsy. His serum TK, which was increased to 11.2 U/l at diagnosis (normal <5 U/l), normalized after glucocorticoid therapy. Serum TK has been considered as a good marker of the proliferative activity of various types of neoplasms. Its rise in sarcoidosis has, however, not been described. Because acute sarcoidosis sometimes resembles malignant lymphoma, the possible rise of serum TK in sarcoidosis may be worthy of note.     

Evaluation of in vitro proliferative activity of human fetal neural stem/progenitor cells using indirect measurements of viable cells based on cellular metabolic activity

To scale up human neural stem/progenitor cell (NSPC) cultures for clinical use, we need to know how long these cells can live ex vivo without losing their ability to proliferate and differentiate; thus, a convenient method is needed to estimate the proliferative activity of human NSPCs grown in neurosphere cultures, as direct cell counting is laborious and potentially inaccurate. Here, we isolated NSPCs from human fetal forebrain and prepared neurosphere cultures. We determined the number of viable cells and estimated their proliferative activity in long-term culture using two methods that measure viable cell numbers indirectly, based on their metabolic activity: the WST-8 assay, in which a formazan dye is produced upon reduction of the water-soluble tetrazolium salt WST-8 by dehydrogenase activity, and the ATP assay, which measures the ATP content of the total cell plasma. We compared the results of these assays with the proliferative activity estimated by DNA synthesis using the 5-bromo-2'-deoxyuridine incorporation assay. We found the numbers of viable human NSPCs to be directly proportional to the metabolic reaction products obtained in the WST-8 and ATP assays. Both methods yielded identical cell growth curves, showing an exponentially proliferative phase and a change in the population doubling time in long-term culture. They also showed that human NSPCs could be expanded for up to 200 days ex vivo without losing their ability to proliferate and differentiate. Our findings indicated that indirect measurements of viable cells based on metabolic activity, especially the ATP assay, are very effective and reproducible ways to determine the numbers of viable human NSPCs in intact neurospheres.     

Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPAR gamma ligand

In our previous study, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, pioglitazone, suppressed both hyperlipidemia and intestinal polyp formation in Apc ¹³⁰⁹ mice at doses of 100 and 200 ppm in the diet. In contrast, it has been reported that doses of 1500 or 2000 ppm of another PPARγ agonist, troglitazone, enhanced colon polyp development in Min mice. In the present study, we therefore investigated the effects of a wide range of pioglitazone doses on both hyperlipidemia and intestinal polyp formation in Min mice. Serum triglycerides and very low density lipoprotein (VLDL) cholesterol in the basal diet group were elevated to levels 13–15 times higher than those in the wild-type counterparts at 20 weeks of age. They were reduced dose-dependently by treatment with 100, 200, 400 and 1600 ppm pioglitazone from 6–20 weeks of age with suppression to almost the wild-type level at the highest dose. Moreover, up-regulation of the liver mRNA levels for lipoprotein lipase (LPL) was evident in the pioglitazone-treated animals. Dose-dependent reduction of intestinal polyps was observed in Min mice given 100–1600 ppm for 14 weeks, total numbers being decreased to 63–9% of the control value. A suppressive effect of pioglitazone on colon polyp formation was also found. The PPARγ agonist, pioglitazone, may thus be a promising candidate chemopreventive agent for colon cancer.     

Possible role of a neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) on stimulus-secretion coupling in catecholamine neuron

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide first isolated from ovine hypothalamic tissue. This peptide stimulates adenylate cyclase activation. However, few details were known of the function of this peptide on stimulus-secretion coupling in neuronal cells. The authors have investigated the role of PACAP on catecholamine biosynthesis and secretion using cultured bovine adrenal chromaffin cells as a model for catecholamine-containing neurons. PACAP38, the 38-amino acid form of PACAP, increased cAMP formation in bovine adrenal chromaffin cells. In addition, PACAP38 increased [Ca2+]i associated with PI turnover and Ca2+ influx into the cells. The synthesis of catecholamine and the phosphorylation of tyrosine hydroxylase, a rate-limiting enzyme of catecholamine biosynthesis, stimulated by the maximal effective concentration of dibutyryl cAMP or a high concentration (56 mM) of K+ were further enhanced by PACAP38. Thus PACAP38 stimulated the pathway of catecholamine biosynthesis mainly by both activation of cAMP- and Ca2(+)-dependent protein kinases. On catecholamine secretion from the cells, the effect of PACAP38 was markedly potentiated by addition of ouabain, an inhibitor of Na+/K+ ATPase. This markedly potentiated secretion was greatly reduced with Na+ omitted-sucrose medium. PACAP38 increased 22Na+ influx into the cells treated with ouabain. Thus PACAP38 with ouabain stimulated catecholamine secretion by accumulation of intracellular Na+, resulting in an increase in Ca2+ influx. These results indicate that the neuropeptide PACAP has an important role in stimulus-secretion coupling in adrenal chromaffin cells.     

Development and application of an Internet-based educational system to share pharmaceutical case reports between pharmacists

For pharmacists to enhance skill of pharmaceutical cares, it is necessary to learn many instructive clinical cases, which include drug-related incidences and checks of medication errors by pharmacists. However, these cases tend to be kept in each facility and there is no access to the cases for outside pharmacists. Therefore, we aimed to develop an internet-based educational system to gather such cases, append educational commentaries by university staffs, and share them between pharmacists. An exclusive site was set up on the world wide web (WWW) homepage of the Section of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University (http://seizai.phar.kyushu-u.ac.jp) on November 2000. Browsing was limited to registered pharmacists. Any pharmacist can be freely registered. Cases were collected via WWW-forms in the site. After educational commentaries and elucidation were appended, the cases were distributed to the registered pharmacists by e-mails and WWW pages. Many applications for membership have been sent from around Japan to have more than 50 members per month, and many cases have been contributed. These cases were distributed weekly by e-mail magazines. The developed system enabled us to share many educational cases of drug-related problems all over the country. This system could contribute to pharmacists to enhance their skills of pharmaceutical cares.     

Relationship between upper limb motor function and activities of daily living after removing the influence of lower limb motor function in subacute patients with stroke: A cross-sectional study

BackgroundPrevious studies have reported a relationship between upper limb motor function and activities of daily living. However, their relationship after removing the influence of lower limb motor function has not been clarified.ObjectiveThis study aimed to investigate the relationship between Fugl-Meyer assessment upper limb and total Functional Independence Measure motor score and between Fugl-Meyer assessment upper limb and each item contained in Functional Independence Measure motor score after eliminating the influence of the motor function of the affected lower limb.MethodsThis retrospective cross-sectional study included 58 subacute stroke patients. To investigate the relationship between the Fugl-Meyer assessment upper limb and total Functional Independence Measure motor score before and after removing the influence of Fugl-Meyer assessment lower limb, Spearman’s rank correlation coefficient and partial correlation analysis were used. Additionally, the relationship between Fugl-Meyer assessment upper limb and each item of Functional Independence Measure motor score after removing the influence was assessed.ResultsBefore removing the influence of Fugl-Meyer assessment lower limb, Fugl-Meyer assessment upper limb was strongly correlated with total Functional Independence Measure motor score (r = 0.74, p < 0.001). However, it became weak after removing the influence (r = 0.27, p = 0.04). Regarding each item of Functional Independence Measure motor score, Fugl-Meyer assessment upper limb was correlated with grooming (r = 0.27, p = 0.04), bathing (r = 0.28, p = 0.03), dressing upper body (r = 0.33, p = 0.01), dressing lower body (r = 0.31, p = 0.02), and stair-climbing (r = 0.31, p = 0.02) after removing the influence.ConclusionThese findings suggest that the relationship between the upper limb motor function and activities of daily living is strongly influenced by lower limb motor function.