Synthesis and intestinal metabolism of ursodeoxycholic acid conjugate with an antiinflammatory agent, 5-aminosalicylic acid

5-Aminosalicylic acid conjugate of ursodeoxycholic acid was synthesized in above 90% yield by adding a basic solution of 5-aminosalicylic acid into the mixed anhydride formed with ursodeoxycholic acid and ethyl chloroformate. The 5-aminosalicylic acid conjugate of ursodeoxycholic acid was poorly secreted into the bile and was deconjugated with cholylglycine hydrolase and Clostridium perfringens, that deconjugate naturally occurring glycine and taurine conjugates of bile acids. However, ursodeoxycholic acid 5-aminosalicylic acid conjugate was not absorbed from the duodenum but was concentrated in the colon where it was partially hydrolyzed by the intestinal bacteria to ursodeoxycholic acid and 5-aminosalicylic acid. We believe that this unique conjugation of ursodeoxycholic acid with 5-aminosalicylic acid may facilitate the transport of both 5-aminosalicylic acid and ursodeoxycholic acid to the colon and may be useful for the treatment of colonic inflammatory bowel diseases, ulcerative colitis and Crohn's disease.     

The beta-gal interferon assay: a new, precise and sensitive method

Cells of a human glioblastoma line were stably transfected with a glial fibrillary acidic protein (GFAP) promoter sequence/lacZ reporter gene. Following this modification, they produced Escherichia coli beta-galactosidase constitutively in amounts that could be measured through their conversion of an added fluorophore into a product readily estimated by fluorimetry. Human interferons (IFN) selectively and in a dose-dependent manner reduce the formation of beta-galactosidase in this system. We have used it as the basis for a novel assay that is sensitive (4-40 pg/ml), precise, completed in 30 h, and applicable to both type I and type II human IFNs. Statistical analysis showed interassay relative standard deviations ranging from 5% to 11%, and most individual assays revealed potencies with limits of error within 85%-115%. Neither partially trypsin-digested IFN nor the other cytokines and mitogens we tested reacted in this system, except for tumor necrosis factor-alpha (TNF-alpha). The high selectivity was further shown by the loss of response to IFN in the presence of the appropriate specific anti-IFN or anti-IFN-gamma receptor antibodies.     

Testicular plasmacytoma following chemical orchiectomy: potential role of hypogonadism in myeloma proliferation

We present a case of a 55 year old man with multiple myeloma who underwent autologous stem cell transplantation and subsequently developed testicular myeloma. Testicular enlargement was observed only after treatment of an incidental prostatic adenocarcinoma with chemical orchidectomy at a time when myeloma was controlled systemically. A subsequent bilateral surgical orchiectomy revealed plasmacytoma in both testis. Enhanced production of B-lymphocytes after castration has been reported and implicates testosterone as a possible negative regulator of B-cell production. We propose that the androgen deficient state may have contributed to the development of plasmacytoma of the testes in our patient. The regulatory role of sex steroids in B-cell development is discussed.     

Double-positive thymocytes resistant to antigen-MHC-induced negative selection lack active caspase

The aim of the current study was to elucidate the synergism of dietary calcium restriction and exhaustive exercise in the antioxidant enzyme system of rat soleus muscle, and to investigate the involvement of neutrophils in exercise-induced muscle damage. Forty-eight male Wistar rats were assigned to the following groups: control (C) or calcium-restricted [1 month (1 M) or 3 months (3 M)]. Each group was subdivided into acutely exercised or non-exercised groups. Soleus muscle from each rat was analysed to determine the levels of antioxidant enzymes [Mn-superoxide dismutase (SOD), Cu, Zn-SOD, glutathione peroxidase (GPX), and catalase (CAT)]. Dietary calcium restriction resulted in calcium deficiency and upregulated the antioxidant enzymes examined except GPX. Conversely, exhaustive exercise significantly decreased GPX and CAT, but not SODs activities in the calcium-restricted (1 M and/or 3 M) rats. Contents of immunoreactive Mn-SOD and Cu,Zn-SOD were only increased in the 3 M rats. During calcium restriction, the mRNA expression of both forms of SOD showed initial upregulation, followed by downregulation. Exhaustive exercise significantly increased the mRNA expressions only in the 3 M rats. Moreover, exhaustive exercise markedly increased myeloperoxidase activity in soleus muscles from the 1 M and 3 M rats compared with the C rats, and significantly enhanced the ability of neutrophils to generate superoxide in the 3 M rats. The results demonstrate that dietary calcium restriction upregulates certain antioxidant enzyme activities in rat soleus muscle, indicating an enhanced resistance to potential increases in intracellular reactive oxygen species. The results also suggest that exhaustive exercise may cause oxidative damage in soleus muscle of calcium-deficient rats through the activation of neutrophils.     

Insulin-dependent diabetes in the county of Funen 1970-2020. An epidemiological description

We present an epidemiological model applicable to insulin-dependent diabetes mellitus (IDDM), based on which prevalence rates are estimated from assumed rates of incidence and mortality of diabetes. The model is illustrated by analysing epidemiological data on IDDM in Fyn County, Denmark for the period 1970-1990, with predictions of prevalence rates during 1990-2020. The epidemiological model assumes known prevalence rates as well as incidence rates and mortality at a given point of time. Under assumed rates of incidence and mortality of IDDM and its complications, the prevalence rate is the dependent variable which is estimated as a function of calendar time. We used epidemiological data on IDDM (operationally defined as insulin-treated diabetes with onset before age 30 years), blindness and nephropathy as well as mortality as reported for the years 1973 and 1987 in Fyn County, Denmark. During 1970-1990 the prevalence of IDDM increased steadily, due to increasing incidence and decreasing risk of complications and mortality. The relative prevalence of patients with nephropathy increased whereas that of blind patients decreased considerably. Under specified assumptions regarding the future levels of incidence of disease, complications and of mortality, it is estimated that the prevalence rate of IDDM in the year 2020 will be 45-60% higher than the level in 1990. The relative prevalence of patients with nephropathy will increase further, whereas the relative prevalence of blind patients will remain constant at a low level. We conclude that IDDM will represent an increasing public health problem in Denmark over the next decades, with increasing overall prevalence rates and a rising proportion of patients with nephropathy. The major determinants of this trend are increasing incidence, combined with declining mortality and declining risk of complications. It is recommended that epidemiological modelling techniques be further developed to provide improved data for the planning of the future diabetes care.     

Optimisation of different physical parameters for bioleaching of phosphate by Aspergillus niger from Indian rock phosphate

A mutant strain of Aspergillus niger AB100 was incubated with samples of rock phosphate. Mutation resulted in a greater amount of solubilisation (30 to 35%) as against the parent strain (10 to 15%). The influence of leaching parameters such as ore concentration (pulp density), particle size, initial pH of the medium, temperature, volume of the medium in 250 ml flasks, inoculum concentration and age of inoculum was studied. When low quantity of rock phosphate is applied (0.1%) the solubilisation of phosphorus was optimal (40.5%). Optimum particle size was--200 to 240 mesh, initial pH of the medium 4.0, optimum volume of the fermentation medium 160 ml, time period of incubation was 8 days, inoculum volume was 7.5 ml, and age of inoculum 7 days. The maximum leaching of phosphorus by using these optimum physical parameters is 45 to 50%.