Anti-urolithiatic effects of Punica granatum in male rats

Ethnopharmacological relevance

The traditional use of Punica granatum has been reported to regulate urine discharge and controls the burning sensation of urine.

Materials and methods

Animals model of calcium oxalate urolithiasis was developed in male rats by adding ethylene glycol 0.75% in drinking water. The Punica granatum chloroform extract (PGCE) and Punica grantum methanol extract (PGME) orally at 100, 200 and 400 mg/kg, respectively, were administered along with ethylene glycol for 28 days. On 28 day, 24 h urine was collected from individual rats and used for estimation of urine calcium, phosphate and oxalate. The serum creatinine, urea and uric acid levels were estimated in each animal. The kidney homogenate was used for the estimation of renal oxalate contents. The paraffin kidney sections were prepared to observe the CaOx deposits.

Results

The ethylene glycol control (Gr.-II) had significant (P < 0.001 vs. normal) increase in levels of urine oxalate, calcium and phosphate, serum creatinine, urea and uric acid and renal tissues oxalates, as compared to normal (Gr.-I). The paraffin kidney sections show significant histopathological changes. The treatment of PGCE and PGME at 100, 200 and 400 mg/kg doses, significantly (P < 0.001 vs. control) decreased the urine oxalate, calcium and phosphate, renal tissue oxalates and serum creatinine, urea and uric acid, in EG induced urolithiasis after 28 days.

Conclusions

The PGCE and PGME at the doses of 400 mg/kg, found to be more effective in decreasing the urolithiasis and regeneration of renal tissues in male rats.     

Optimizing dose and scheduling of filgrastim (granulocyte colony- stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers [see comments]

To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients.     

AUF1 is upregulated by angiotensin II to destabilize cardiac Kv4.3 channel mRNA

Expression of cardiac myocyte Kv4 channels (Kv4.3 for human, Kv4.2 and Kv4.3 for rodents) is downregulated with hypertrophy in vivo leading to a decrease in the transient outward current (Ito). This effect is recapitulated in vitro with rat neonatal cardiac myocytes treated with angiotensin II (Ang II), which acts via AT₁ receptors, NADPH oxidase and p38 MAP kinase to destabilize the 3′ untranslated region (3′UTR) of the Kv4.3 channel messenger RNA (mRNA). Here deletion analysis and mutagenesis identify an AU-rich element (ARE) in the Kv4.3 3′UTR that is required for Ang II-induced destabilization. Overexpression of AUF1 (ARE/poly-(U)-binding/degradation factor 1), an RNA destabilizing protein, mimics and occludes the Ang II effect, while RNA interference targeted against AUF1 blocks the Ang II effect on the Kv4.3 3′UTR. Ang II upregulates AUF1 by activating AT₁ receptors, NADPH oxidase and p38 MAP kinase. Finally, pull-down assays establish that Ang II increases AUF1 binding to the ARE required for destabilization, while binding of the mRNA stabilizing protein HuR is unaffected. Hence, Ang II acts via AT₁ receptors, NADPH oxidase and p38 MAP kinase to upregulate AUF1, which in turn binds to an ARE in the Kv4.3 3′UTR to destabilize the channel mRNA.     

Evaluation of Factors in Relation with the Non-Compliance to Curative Intent Radiotherapy among Patients of Head and Neck Carcinoma: A Study from the Kumaon Region of India

Introduction:

Radiotherapy (RT)-based curative regimens for head and neck squamous cell carcinomas (HNSCC) deliver a dose of 66–70 Gray (Gy) over a period of 6–7 weeks, and incomplete treatments are unlikely to result in cure. Non-compliance to RT is major contributory factor to treatment failure.

Aims:

To assess the proportion of patients who do not complete planned treatment after initiation of curative RT. This study also aims to explore a possible relationship of non-compliance due to socio-economic, disease-related and treatment-related factors.

Materials and Methods:

The records of HNSCC patients treated from January 2012–December 2013 were audited. Data from the treatment records were to collect patient-related, disease-related, and social demographic parameters. Of the patients who had not completed treatment, the reasons behind the same were investigated.

Results:

Of the 324 patients of HNSCC who were initiated on radical RT, a total of 76 patients were found to have discontinued treatment without authorization of the treating clinician. There was no significant predilection for treatment non-compliance with regards to patient age, educational status, religion, site of the disease, use of neoadjuvant chemotherapy, or use of concurrent chemotherapy. There tended to be a higher association of treatment non-compliance among patients residing >100 km away from the treatment center, patients hailing from hilly regions, patients without the below poverty line (BPL) card, unemployed patients, and patients with stage IV-A/B disease. Of the 76 patients who did not complete treatment, telephonic questionnaire could be obtained from 54 patients. Causes for non-compliance included preference for traditional healers (22.2%), fear of toxicity (7.4%), logistic reasons (18.5%), financial reasons (24.1%), and lack of interest/faith in RT (5.6%).

Conclusion:

There is a high incidence of treatment default among patients of HNSCC during RT in this region. The revelation of the higher propensity for treatment default among patients from distant, hilly regions, unemployed, patients without BPL cards, and stages-IVA/IVB highlights the need for specific interventions for these special populations.