New bone formation and osteolysis by a metastatic, highly invasive canine prostate carcinoma xenograft

BACKGROUND: Osteoblastic metastases are commonly induced by prostate cancer. A canine prostate carcinoma xenograft (Ace-1) was developed and used to evaluate neoplastic prostate cell growth, metastasis, and effects on bone formation in nude mice. METHODS: Characteristics of the Ace-1 cells were evaluated with histopathology, radiography, and bioluminescent imaging (BLI). Immunohistochemistry and quantitative RT-PCR were used to evaluate the expression of factors important in the development of osteoblastic metastases. RESULTS: The Ace-1 cells were invasive and induced bone formation and destruction. Radiographs demonstrated a mixed osteoblastic/osteolytic reaction. Lung and lymph node metastases occurred in 30% of mice. The tumor cells expressed parathyroid hormone-related protein (PTHrP-141 isoform), cathepsin K, keratins 8/18, and vimentin, but not keratins 5/14, and were androgen receptor negative. Intracardiac (IC) injections resulted in metastases in vertebrae and long bones. CONCLUSIONS: The Ace-1 xenograft is a useful model for investigating the pathogenesis of prostate cancer invasion and mixed osteoblastic/osteolytic bone metastases.     

Evaluation of antihyperglycemic activity of methanolic Tecomaria capensis Thunb. (Bignoniaceae) leaves extract in alloxan induced hyperglycemic rats

ObjectiveTo evaluate the antihyperglycemic activity of Tecomaria capensis (T. capensis) Thunb. (Bignoniaceae) methanolic leaves extract (TCLE) using blood glucose level in normal fasted rats, glucose tolerance test and alloxan induced hyperglycemia models.MethodsTCLE (100, 300, 1 000 and 2 000 mg/kg body wt.) was given to rats orally to observe acute toxicity, and observed for 14 d. TCLE 200 and 400 mg/kg, and glibenclamide 0.6 mg/kg were given orally in all models.ResultsResults demonstrated that the no mortality was reported even after 14 d. This indicates that the methanol extract is safe up to a single dose of 2 000 mg/kg body weight. TCLE (200 and 400 mg/kg p.o.) exhibited remarkable blood glucose lowering effect in blood glucose level in normal fasted rats, glucose tolerance and alloxan induced hyperglycemia model. Cholesterol and triglyceride also decreased in alloxan induced hyperglycemia model.ConclusionsThe results of this study exhibites that methanol extract of T. capensis possesses antihypergycemic activity and it may prove to be effective for the treatment of hyperglycemia.     

PLASMID MEDIATED DRUG RESISTANCE IN VIBRIO CHOLERAE 0139 BENGAL

Sixteen strains of Vibrio cholerae were isolated from cases of diarrhoea. Out of these, 12 (75%) were identified as Vibrio cholerae 0139 synonym Bengal and 4 (25%) as Vibrio cholerae El Tor by standard biochemical and serological tests. Modified CAMP reaction in sheep blood agar showed that 0139 produced moderate hemolysis, El Tor produced wider zone of hemolysis whereas Classical Vibrio cholerae produced no zone of hemolysis (CAMP negative). Break point minimum inhibitory concentration (MIC) by agar dilution method showed that all 0139 strains were resistant to ampicillin 8 mg/L, streptomycin 1 mg/L, chloramphenicol 8 mg/L, sulphamethoxazole 32 mg/L and trimethoprim 0.3-128 mg/L, 58.3% were sensitive to gentamicin 1 mg/L, and all were sensitive to norfloxacin 1 mg/L and cefotaxime 1 mg/L. Resistance to trimethoprim, sulphamethoxazole, ampicillin and gentamicin in 5 strains could be transferred to E coli K-12 by conjugation experiment at a rate of 5×10⁻⁶ to 4×10⁻³. Distinct plasmid bands of 35.8 mega daltons could be seen in agarose gel electrophoresis.KEY WORDS: CAMP test, Drug resistance, Plasmid, Vibrio cholerae 0139.     

Bioequivalence studies of tacrolimus capsule under fasting and fed conditions in healthy male and female subjects

The bioequivalence of tacrolimus (CAS 104987-11-3) 5 mg capsules was assessed in two single-dose, open-label, randomIzed 2-way crossover trials with a minimum washout period of 14 days; one trial was conducted under fasting condition (n = 44) and the other one under fed condition (n = 48). Blood samples were collected over a 120-h period and concentrations were assayed using a liquid chromatography tandem mass spectrometry (LCMS/MS) method. A non-compartmental method was used for calculation of pharmacokinetic parameters. Under fasting conditions, mean AUC(0-t), AUC(0-inf) and C(max) were comparable between the test (296 ng x h/mL, 318 ng x h/mL and 32 ng/ mL, respectively) and the reference formulations (289 ng x h/mL, 309 ng x h/mL and 33 ng/mL, respectively). T(max) was reached between 1.5 and 2 h post-dose. Mean AUC(0-t), AUC(0-inf) and C(max) were also comparable under fed conditions (154 ng x h/mL, 169 ng x h/mL and 7.6 ng/mL, respectively, for the test and 161 ng x h/mL, 176 ng x h/mL and 7.5 ng/mL, respectively, for the reference formulation). Under fed conditions, T(max) was reached between 5 and 6 h post-dose. 90% geometric confidence intervals were all within the acceptable 80-125% limit, suggesting bioequivalence between the generic product and the innovator product.