Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas

We previously detected elevated transforming growth factor beta-1 (TGF-beta1) serum levels in patients with invasive bladder carcinomas. In this study, we therefore investigated whether elevated serum levels correlate with enhanced TGF-beta expression in human bladder tumours. mRNA levels of TGF-beta1, -beta2 and -beta3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of the levels in normal urothelium. On the other hand, TGF-beta1 protein levels were found to be higher in superficial tumours (Ta-T1) (mean level of 0.153 ng mg(-1)) and in invasive T2/T3 tumours (mean level of 0.104 ng mg(-1)) compared with normal urothelium (mean level of 0.065 ng mg(-1)). Invasive T4 tumours, however, contained only low amounts of TGF-beta1 (mean level of 0.02 ng mg(-1)). Neither in mean nor in individual patients were serum and tissue TGF-beta levels correlated with each other. Cell culture experiments on primary bladder cells revealed a 57% decrease in TGF-beta1 mRNA levels in tumour compared with normal epithelial cells. Tumour epithelial cells contained about two times higher levels of TGF-beta2 and TGF-beta3 mRNA than normal epithelial cells. Fibroblasts expressed about the same amount of TGF-beta1 or TGF-beta2 as epithelial cells. Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour epithelial cells into the supernatant. TGF-beta3, on the other hand, was expressed by fibroblasts with higher levels than by epithelial cells. TGF-beta1 was the predominent isoform in bladder tissue and cells at protein as well as on mRNA levels indicating that TGFs-beta2 and -beta3 are of minor importance in bladder cancer. In summary, there is a lack of correlation between TGF-beta serum levels and TGF-beta expression in tumour tissue in bladder cancer.     

Low nutritional quality of unconventional tropical crop seeds in rats

As the search for alternative sources of food to alleviate hunger continues, this study was undertaken to determine the biological value in growing rats (BV) of proteins of some lesser known tropical seeds gathered in Nigeria. Antinutritional factors (trypsin inhibitors, phytic acid, oxalate, tannin, alkaloids) and amino acid compositions were also determined, and protein digestibility-corrected amino acid score (PDCAAS) was calculated using the amino acid requirement pattern of the preschool child and individual seed-specific correction factors for crude protein. A rat growth and balance study was conducted to determine digestibility, nitrogen-, and energy balance by feeding as the only unsupplemented protein source milled and heat-treated seeds of Adansonia digitata (Bombacaceae) and Prosopis africana, Lonchocarpus sericeus, Enterolobium cyclocarpium, Sesbania pachycarpa and Pterocarpus osun (Leguminosae) in comparison to casein fortified with methionine (control). Diets containing P. africana and L. sericeus seeds caused poor feed intake and weight loss in rats and were excluded from the nitrogen-balance test. Among the seed samples, S. pachycarpa followed by A. digitata showed the most advantageous nutritional quality [amino acid composition, digestibility, BV and net protein utilization (NPU)]. True digestibility was 82.9 and 74.5 vs. 98.5, BV was 64.6 and 70.0 vs. 90.4, and NPU was 53.5 and 52.1 vs. 89.0 for S. pachycarpa and A. digitata vs. casein (control), respectively. In terms of PDCAAS, lysine was the first limiting amino acid for S. pachycarpa (88%) and for A. digitata (58%). The PDCAAS of all essential amino acids was below 100% for E. cyclocarpium (e.g., cysteine + methionine: 37%) and for P. africana (e.g., threonine: 46%, except valine and a very high content of cysteine and methionine). In conclusion, all seeds tested in the rat balance trial were of inferior quality compared to casein. Before these tropical seeds could be used as food components or feed supplements, safety studies and proper processing to remove antinutritional factors and possible toxic constituents were required.     

Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects

OBJECTIVES: The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients. Since in vitro replication of HIV is increased with oxidative stress, this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans. DESIGN: A randomized placebo-controlled, double-blind study. METHODS: Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. New or recurrent infections for the 6-month period after study entry were also recorded. RESULTS: The vitamin group (n = 26) had an increase in plasma concentrations of alpha-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P < 0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23). There was also a trend towards a reduction in viral load (mean +/- SD changes over 3 months, -0.45 +/- 0.39 versus +0.50 +/- 0.40 log10 copies/ml; P = 0.1; 95% confidence interval, -0.21 to -2.14). The number of infections reported was nine in the vitamin group and seven in the placebo group. CONCLUSION: Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.     

Oligomers of the Cdc7/Dbf4 protein kinase exist in the yeast cell

1. The amnesia induced by various stress stimuli through hypoxia and cerebral ischemia was evaluated by the shortening of the response latency in a step-through task in mice. 2. The hypoxia-induced amnesia was reduced by cromakalim, a K+ channel opener (KCO), given 10 min before or immediately after the hypoxic treatment. 3. Similarly, the ischemia-induced amnesia was also reduced by cromakalim given 30 min before the occlusion. 4. In ischemic-induced amnesic mice, pyknotic cells, indicating the condensation of chromatin, were observed histochemically at the dentate gyrus granule cells in hippocampal regions 96 hr after ischemic treatment. In addition, cromakalim inhibited the induction of pyknotic cells. 5. These results suggest that KCOs might produce prophylactically neuroprotective effects against hypoxia- and cerebral ischemia-induced amnesia.     

Clinical immunological classification of tuberculous uveitis

Clinical and immunological studies carried out in 251 patients with tuberculous uveitis (TU) revealed three types of inflammatory reactions in the uveal tract in this patient population: productive, exudative, and productive-exudative (mixed), differing by the type of immune disorders. The findings helped develop a clinical immunological classification of TU, taking account of the clinical form of uveitis, type of inflammatory reaction of the uveal tract, disease pattern, involvement of one or both eyes, complications, and the immunopathological variants of TU course.     

Kinetic study on the degradation of prazepam in acidic aqueous solutions by high-performance liquid chromatography and fourth-order derivative ultraviolet spectrophotometry

A reversed-phase HPLC method was developed for the kinetic investigation of the acidic hydrolysis of prazepam which was carried out in hydrochloric acid solutions of 0.01, 0.1 and 1.0 M. In addition, a fourth-order derivative method for monitoring the parent compound itself was proposed and evaluated. One intermediate was observed by HPLC, which should be formed from breakage of the azomethine linkage. Further slow hydrolysis of the amide bond led to the benzophenone product that was isolated and identified. The mechanism of hydrolysis was biphasic, showing a consecutive reaction with a reversible step. Relative standard deviation was less than 2% for HPLC and less than 5% for the derivative method. Detection limits were 1.2 x 10(-7) M for the former method and 6.7 x 10(-7)M for the latter. Accelerated studies at higher temperatures were employed. Results of HPLC and fourth-order derivative methods were statistically the same.     

Chemotherapeutics for treatment of influenza and other viral respiratory tract infections in children

Regardless of the primary care model used in the long-term care facility, each of the three approaches offers quality care improvement and greater consistency for residents at reduced costs. Of the three, an all licensed nursing staff model could best meet the higher acuity levels of residents and the disintegrating availability of qualified nursing assistants. If nurses are unable to "sell" this model to administration, it may be helpful to pilot the concept one one unit for a period of time and compare resident, family, and staff satisfaction with that of a similar unit. Also, it is critical to compare the financial implications, including cost per resident per day and rate of staff turnover, to weigh the model's effectiveness. This small sampling of five facilities indicates the average cost per resident per day is $10 less when using either the primary team or all licensed staff models than in facilities of comparable size. Hospitals have already passed the time when they have had to work smarter, leaner, and more efficiently. Can long-term care facilities afford not to do the same?     

Placental mitochondrial DNA and respiratory chain enzymes in the etiology of preeclampsia

OBJECTIVE: To evaluate the occurrence of the most common mutations and deletions in mitochondrial DNA and deficiencies in the enzyme complexes of the mitochondrial respiratory chain in placentas from preeclamptic women. METHODS: Mitochondria were isolated from the placentas of 17 preeclamptic or 25 control women, and the activities of mitochondrial respiratory chain complexes were measured. Deletions and three common point mutations of mitochondrial DNA were searched for by the Southern blot and polymerase chain reaction (PCR) methods from the same placentas. RESULTS: Mean (+/- standard deviation) mitochondrial respiratory chain enzyme complex activities in placentas on protein basis (nmol/min/mg of protein) were similar in preeclamptics and controls (nicotinamide adenine dinucleotide, reduced form-ubiquinone oxidoreductase 25.84 +/- 9.29 versus 31.02 +/- 7.52; nicotinamide adenine dinucleotide, reduced form-cytochrome-c oxidoreductase 77.88 +/- 42.24 versus 104.06 +/- 56.73; succinate-cytochrome-c oxidoreductase 57.90 +/- 13.83 versus 64.44 +/- 20.16; cytochrome-c oxidase 106.43 +/- 35.46 versus 128.37 +/- 48.64, respectively) and they were similar also when referenced to the mitochondrial marker enzyme citrate synthase. The sample sizes in both patient and control groups were found to be large enough by post hoc test. Large-scale deletions or the common 5-kb and 7.4-kb deletions were not detected, even at the sensitivity level of PCR. The three most common point mutations were not found in either control or preeclamptic placental samples. CONCLUSION: Common mitochondrial DNA mutations seem to play no major role in the universal etiology of preeclampsia, as assessed by analysis of the mitochondrial genome and respiratory chain enzyme activities in vitro. This does not exclude possible alterations in the energy state of the preeclamptic placenta.     

Selectivity in capillary electrophoresis in the presence of micelles, chiral selectors and non-aqueous media

In addition to high efficiency, short analysis times and small sample volumes, a further attractive feature of capillary electrophoretic techniques is the possibility to achieve, high selectivities. Usually, selectivity control also allows improvement in the resolution. A simple way to enhance the selectivity of capillary electrophoretic separations is to add one or more surfactants above their critical micelle concentration, or in the case of chiral separations to add a chiral selector to the background electrolyte. Because of the dynamic structure of micelles, the aggregation of monomers and size of the micelles can be easily adjusted. This review describes the various type of surfactants used in micellar electrokinetic capillary chromatography, and the chiral selectors employed in enantiomeric separations by capillary electrophoresis. Factors affecting the selectivity are noted. A brief discussion is included of the selectivity enhancement obtainable in non-aqueous media.