Aging changes agonist induced contractile responses in permeabilized rat bladder

Aging alters bladder functions where a decrease in filling, storage and emptying is observed. These changes cause urinary incontinence, especially in women. The aim of this study is to examine how aging affects the intracellular calcium movements due to agonist-induced contractions in permeabilized female rat bladder. Urinary bladder isolated from young and old female Sprague-Dawley rats were used. Small detrusor strips were permeabilized with β-escin. The contractile responses induced with agonists were compared between young and old groups. Carbachol-induced contractions were decreased in permeabilized detrusor from old rats compared to young group. Heparin and ryanodine decreased carbachol-induced contractions in young rats where only heparin inhibited these contractions in olds. Caffeine-induced contractions but not inositol triphosphate (IP₃)-induced contractions were decreased in old group compared to youngs. The cumulative calcium response curves (pCa 8–4) were also decreased in old rats. Carbachol-induced calcium sensitization responses did not alter by age where GTP-β-S and GF-109203X but not Y-27632 inhibited these responses. Carbachol-induced contractions decrease with aging in rat bladder detrusor. It can be postulated as IP₃-induced calcium release (IICR) is primarily responsible for the contractions in older rats where the decrease in carbachol contractions in aging may be as a result of a decrease in calcium-induced calcium release (CICR), rather than carbachol-induced calcium sensitization.     

Systematic review of the treatment of cancer-associated anorexia and weight loss.

PURPOSE: We systematically assessed the efficacy and safety of appetite stimulants in the management of cancer-related anorexia. Literature databases were searched for randomized controlled trials of appetite stimulants in the treatment of cancer anorexia. MATERIALS AND METHODS: Studies were graded according to quality. Fifty-five studies met inclusion criteria. RESULTS: Only two drugs have evidence to support their use for anorexia (progestins and corticosteroids). There is strong evidence against the use of hydrazine sulfate. The outcomes of these trials have been mixed and patient population heterogeneous. CONCLUSION: The optimal dose, time to start, and duration of treatment for many appetite stimulants for cancer anorexia is still unknown. A more systematic approach to research methodology with universal outcome measure and prospective randomized studies are need. Combination regimens are needed but this cannot at the present time be supported by the data presented.     

Detection and genotyping of oocysts of Cryptosporidium parvum by real-time PCR and melting curve analysis

Several real-time PCR procedures for the detection and genotyping of oocysts of Cryptosporidium parvum were evaluated. A 40-cycle amplification of a 157-bp fragment from the C. parvum beta-tubulin gene detected individual oocysts which were introduced into the reaction mixture by micromanipulation. SYBR Green I melting curve analysis was used to confirm the specificity of the method when DNA extracted from fecal samples spiked with oocysts was analyzed. Because C. parvum isolates infecting humans comprise two distinct genotypes, designated type 1 and type 2, real-time PCR methods for discriminating C. parvum genotypes were developed. The first method used the same beta-tubulin amplification primers and two fluorescently labeled antisense oligonucleotide probes spanning a 49-bp polymorphic sequence diagnostic for C. parvum type 1 and type 2. The second genotyping method used SYBR Green I fluorescence and targeted a polymorphic coding region within the GP900/poly(T) gene. Both methods discriminated between type 1 and type 2 C. parvum on the basis of melting curve analysis. To our knowledge, this is the first report describing the application of melting curve analysis for genotyping of C. parvum oocysts.     

The Clinical Value of the Ratio of Free Prostate Specific Antigen to Total Prostate Specific Antigen

Objective: To examine the usefulness of the ratio of free prostate specific antigen (FPSA) to total prostate specific antigen (TPSA) in men with serum TPSA concentration of 4 to 10 ng/mL by using the cut off value of 0.15 for avoiding unnecessary biopsies. Patients and methods: Two hundred thirty-six men aged between 52 and 91 with symptoms of prostatism were evaluated with digital rectal examination (DRE), FPSA and TPSA measurements. Patients with TPSA values under 4 ng/mL were biopsied if they had positive DRE and/or a FPSA/TPSA ratio lower than 0.15. All patients with TPSA values higher than 4 ng/mL were also biopsied. The predictive value and sensitivity of FPSA/TPSA ratio and TPSA alone were calculated. Results: Eleven patients out of 170 with a TPSA value lower than 4 ng/mL were biopsied. Fifty-five patients had a value between 4.1 and 10 ng/mL. We performed transrectal ultrasound (TRUS) and prostate biopsy in these men except one patient. Biopsy proven prostate cancer was detected only in 12 patients. In this group of patients the predictive value of TPSA was 21%, but the predictive value of FPSA/TPSA ratio of 0.15 was 78% maintaining at least 90% sensitivity. Eleven of the patients had a prostate specific antigen (PSA) value higher than 10 ng/mL. In 6 of these patients the biopsy result was prostate cancer and 10 of these patients had a FPSA/TPSA ratio lower than 0.15. Conclusion: In patients with TPSA values between 4–10 ng/mL the cut off value of FPSA/TPSA ratio of 0.15 can be used to eliminate unnecessary biopsies with minimal loss of cancer patients.     

Survivin and aven: two distinct antiapoptotic signals in acute leukemias.

BACKGROUND: Antiapoptotic signals are important in the development, progression and prognosis of malignant tumors. The aim of this study was to determine the two distinct antiapoptotic signals-survivin and aven-in acute leukemias and compare them with clinical and hematological findings and response to therapy. Real-time quantitative PCR was used and survivin and aven were detected at the messenger (m)RNA level. PATIENTS AND METHODS: Sixty-five patients with acute leukemia [37 with acute myeloblastic leukemia (AML) and 28 with acute lymphoblastic leukemia (ALL)] were used as the study group and 10 healthy subjects were used as the control group. RESULTS: Survivin was between 0.0 and 0.829 copy number/cell (median 0.0721, mean 0.5424301909 +/- 0.139799488589) and aven was between 0.0 and 0.853 copy number/cell (median 0.0124, mean 0.070335542 +/- 0.1524685709). We found an important association between survivin and aven (P = 0.000). Both survivin and aven were higher in the study group than in the controls (P = 0.001 and 0.035, respectively). When we compared survivin and aven with other clinical and hematological parameters, there was an important association between survivin and extramedullary involvement (P = 0.033), survivin and alkaline phosphatase (P = 0.06), white blood cell (WBC) count and lactate dehydrogenase (LDH) (P = 0.000), WBC count and uric acid (P = 0.074), hemoglobin level and LDH (P = 0.072), LDH and uric acid (P = 0.057), CD7 expression and survivin (P = 0.097), and CD34 expression and aven (P = 0.058). Response to therapy was evaluated according to the survivin and aven levels. Survivin level was lower in refractory patients as compared with complete responders (P = 0.085). Aven level was higher in patients with relapse as compared with non-relapse patients (P = 0.04). There was no important association between survivin or aven and performance status, lymphadenopathy or organomegaly. CONCLUSIONS: Both survivin and aven are important antiapoptotic signals in acute leukemias, and the association between extramedullary involvement, CD7 expression and CD34 expression, which are important poor prognostic indicators in acute leukemias, suggests that survivin and/or aven may be novel prognostic indicators in acute leukemias. Further studies with a higher number of patients will be more informative.