Piperine (1), an alkaloid of black and long peppers, inhibited gastric emptying (GE) of solids/liquids in rats and gastrointestinal transit (GT) in mice in a dose and time dependent manner. Compound ...1 significantly inhibited GE of solids and GT at the doses extrapolated from humans (1 mg/kg and 1.3 mg/kg p.o. in rats and mice, respectively). However, at the same dose the effect was insignificant for GE of liquids. One week oral treatment of 1 mg/kg and 1.3 mg/kg in rats and mice, respectively, did not produce a significant change in activity as compared to single dose administration. GE inhibitory activity of 1 is independent of gastric acid and pepsin secretion.
Abstract Background BK nephropathy (BKN) is an important complication of renal transplantation, with a reported incidence between 1% and 10% in different parts of the world. Known risk factors for ...the development of BKN are the recently introduced immunosuppressants and steroids. However, the preexisting viral load may add to the risk for development of BKN. Therefore, the present study was designed to monitor the baseline BK virus (BKV) DNA in renal transplant donors and recipients in India for correlation with the development of BKN. Methods This study used real-time polymerase chain reaction (PCR) for quantification of BKV DNA in the plasma of kidney transplant donors (n = 38) and recipients (n = 87) at the time of surgery. The control BKV DNA was manufactured from a known positive human sample, by cloning a 133-bp PCR product of bases 4,329 to 4,462 of the large T-antigen (TAg) of BKV in a plasmid vector. Results Twenty-five of 87 recipient (28.7%) and 17/38 donor (44.7%) plasma samples were positive for BKV DNA at the time of transplantation with a median viral load of 910 (range 49–4770) and 312 (range 79–1508) copies per mL plasma, respectively. Six of 38 donor-recipient pairs showed viremia in both the recipient and donor: 1 developed histologically proven BKN at 18 months, 1 showed positive immunohistochemistry for SV40 TAg, and 2 others had high levels of viremia (14,545 copies at 6 and 2,617,524 copies at 3 months). None of the other 81 recipients showed evidence of BKN in the follow-up period. Conclusions This study showed that 28% of recipients and 44% of donors displayed baseline positivity for BKV DNA in plasma, which is higher than the reported incidence in the West. The baseline levels of BKV DNA in recipients with end-stage renal disease were higher than in donors. Dual positivity for BKV DNA in the plasma of donor-recipient pairs conferred a high risk of development of BK nephropathy in the allografted kidney.
Objective: The purpose of this study was to determine the rates of obstetric hemorrhage and maternal mortality in women who are Jehovah's Witnesses and to evaluate a protocol that uses erythropoietin ...to optimize the red blood cell mass before delivery. Study Design: Obstetric outcomes were described for all of the women who were Jehovah's Witnesses and who delivered at Mount Sinai Medical Center during an 11-year period. The risk of maternal death was compared with our general obstetric population during this interval. Results: A total of 332 women who were Jehovah's Witnesses had 391 deliveries. An obstetric hemorrhage was experienced in 6% of this population. There were 2 maternal deaths among the women who were Jehovah's Witnesses, for a rate of 512 maternal deaths per 100,000 live births versus 12 maternal deaths per 100,000 live births (risk ratio, 44; 95% CI, 9-211). Erythropoietin was associated with a nonsignificant increase in hematocrit level. Conclusion: Women who are Jehovah's Witnesses are at a 44-fold increased risk of maternal death, which is due to obstetric hemorrhage. Patients should be counseled about this risk of death, and obstetric hemorrhage should be aggressively treated, including a rapid decision to proceed to hysterectomy when indicated. (Am J Obstet Gynecol 2001;185: 893-5.)
The mucoadhesion, swelling, and drug release behavior of polyethylene oxide (PEO) and carbopol (CP) matrices were studied using a water soluble model drug diltiazem hydrochloride. The mucoadhesive ...strength of the matrices increased with increase in polymer content. The results showed that PEO was more mucoadhesive than CP. Mucoadhesion of the tablets was dependent upon the swelling. Swelling was ascertained by measuring the axial and radial expansion of matrix tablets following exposure to media of physiological ionic strength. There was a marked increase in the swelling index of matrices containing high polymer content of PEO as compared to CP. Drug release kinetics were found to be closely related to dissolution and swelling properties of the matrices. The release was found to be non-fickian with n (release exponent) values ranging from 0.45-0.58. At a constant polymer content (15.84% w w), the main contributing factor for the mucoadhesion, swelling, and release was the amount of PEO.
Cell therapies hold immense promise for revolutionizing medical treatments. However, cell therapy products, manufactured and stored under cryogenic conditions, require robust transportation systems ...to maintain their quality and integrity. In the context of genetically-engineered cell therapies like CAR-T, it becomes particularly important, given the personalized nature of these therapies. Our analysis of real-world data from one of Canada's most active investigational cell therapy products’ (IP) sites sheds light on the robustness of current cold chain transportation processes.
This is a retrospective observational study to analyze temperature data from external IP shipments and institutional transportation. Data points from two major cryogenic shipment service vendors (V1 and V2) for shipment from contract manufacturing organizations (CMO) to the on-site cryostorage, and from cryogenic transportation of IP to patient bedside were included. Ten shipments across North America using various mode of travel and spanning a range of delivery times were analyzed from each service vendor, along with ten institutional transports. Mean median payload and external dry shipper temperatures were evaluated and compared. Data was analyzed for statistical significance.
Thirty shipment temperature data (20 vendor provided; 10 institutional transports) were analyzed. The mean times of IP shipments from CMO to hospital site were 52.8±13.6hrs (V1); and 39.1±16.6hrs (V2). For all vendor shipments, the mean median payload temperature was -191.5±3°C, –191.3°C; and external temperature was 15.3±4.4°C 15.5°C. Between vendors, the mean median payload temperatures were V1:-195.2±0.7°C -195.1°C and V2:-187.8±0.9°C -188.1°C, well below the target range (<-150°C). The correlation analysis of external temperatures (V1:12.7±1.7°C; V2:17.9±3.9°C) showed no correlation with payload temperature. Dry shipper mean median temperatures during institutional transport to patient bedside was -173.0±2.1°C -173.2°C, well below the target range (<-150°C) and the mean time of transport is 68.6±29.8min.
This analysis found no payload temperature excursions during IP shipments and transports. Payload temperature between vendors is similar and within regulation but the difference is statistically significant. Our analysis of real world data validates that current cold chain shipment and transport processes for cell therapy IP are robust and fit for purpose.
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