Is Ciprofloxacin a Substrate of P-glycoprotein?

INTRODUCTION: Studies using MDCKII and LLC-PK1 cells transfected with MDR1 cDNA indicate that ciprofloxacin is not a substrate of P-glycoprotein. However, our data has shown that transport studies done using different P-gp overexpressing cell lines (MDCKI-MDR1, MDCKII-MDR1 and L-MDR1), could lead to contradictory conclusion on whether a compound is a substrate of P-gp. The aim of our study was to determine if ciprofloxacin is indeed not a P-glycoprotein substrate using MDCKI cells transfected with human MDR1 cDNA. METHODS: Semi-quantitative RT-PCR was used to determine the mRNA level of MDR1 while Western blot was performed to determine the protein expression level of P-gp, MRP1 and MRP2 in various cells. Ciprofloxacin bidirectional transport studies were performed in MDCKI, MDCKI-MDR1, MDCKII, MDCKII-MDR1, MDCKII-MRP2, LLC-PK1, L-MRP1 and L-MDR1 cells. RESULTS: Ciprofloxacin showed net secretion in MDCKI-MDR1 but net absorption in MDCKI cells. Various P-gp inhibitors decreased the B to A and increased the A to B transport of ciprofloxacin in MDCKI-MDR1 cells while having no effect in MDCKI cells. The B to A transport of ciprofloxacin in MDCKI-MDR1 cells was not affected by non-P-gp inhibitors. In the presence of indomethacin, ciprofloxacin showed net secretion instead of net absorption in MDCKI cells while in the presence of probenecid and sulfinpyrazone, there was no net secretion and absorption. There was no difference in ciprofloxacin transport between MDCKII and MDCKII-MDR1, LLC-PK1 and L-MDR1, LLC-PK1 and L-MRP1 and MDCKII and MDCKII-MRP2. CONCLUSIONS: Transport data in MDCKI and MDCKI-MDR1 cells indicate that ciprofloxacin is a substrate of P-gp but data from MDCKII, MDCKII-MDR1, LLC-PK1 and L-MDR1 cells indicate that ciprofloxacin is not a substrate of P-gp. Vinblastine, a well-known P-gp substrate, also did not show differences between LLC-PK1 and L-MDR1 cells. Further studies need to be performed to characterize these P-gp overexpressing cell lines and the transport of ciprofloxacin.     

Hepatic immunosuppressive effects of systemically administered novel dextran-methylprednisolone prodrugs with peptide linkers in rats

The hepatic immunosuppressive activities of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP1) or five (DMP5) amino acids as linkers were studied in rats. At various times (0–2 weeks) after intravenous administration of single 5 mg/kg (MP equivalent) doses of each prodrug or MP succinate (MPS), livers were isolated and immunologically stimulated ex vivo with lipopolysaccharide. The concentrations of tumor necrosis factor (TNF)‐α in the outlet perfusate were then quantitated to assess immune response. Additionally, the concentrations of DMP1, DMP5, and/or MP were measured in the liver. MPS, DMP5, or DMP1 injections caused a maximum of 48.9%, 63.5%, or 85.7% decrease in the TNF‐α secretion into the perfusate, with the time above the 50% inhibitory effect being <5, <24, or 120 h, respectively. Additionally, the area under the effect–time curve for DMP1 was 11‐fold or fourfold higher than that after the administration of MPS or DMP5, respectively. Relatively high concentrations of DMP1 were present in the liver even at the last sampling time of 2 weeks. These data suggest that a single intravenous dose of DMP1 produces an intense and sustained immunosuppression in the liver for a relatively long time, which may be useful in liver transplantation.     

Antinociceptive activity of methanol extract of flowers of Impatiens balsamina

Ethnopharmacological relevance

Impatiens balsamina Linn. (Balsaminaceae), an annual herb locally called “Dopati”, is cultivated as an ornamental garden plant in Bangladesh. Flowers of the plant are used in folk medicine to treat lumbago, neuralgia, burns and scalds.

Aim of the study

This study evaluated the antinociceptive effect of the methanol extract of I. balsamina flowers (MIB).

Materials and methods

The extract was evaluated for antinociceptive activity using chemical- and heat-induced pain models such as acetic acid-induced writhing, hot plate, tail immersion and formalin test. To verify the possible involvement of opioid receptor in the central antinociceptive effect of MIB, naloxone was used to antagonize the effect. The effect of MIB on central nervous system (CNS) was also studied using hole cross and open field tests.

Results

MIB demonstrated strong and dose-dependent antinociceptive activity in all the chemical- and heat-induced mice models (p<0.05). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. The use of naloxone confirmed the association of opioid receptors in the central antinociceptive effect. MIB also showed significant central nervous system depressant effect (p<0.05).

Conclusion

This study reported the peripheral and central antinociceptive activity of the flowers of I. balsamina and rationalized the traditional use of the flower in the treatment of different painful conditions.     

Stimuli-sensitive hydrogels: A novel ophthalmic drug delivery system

Background:

Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change.

Aim:

To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration.

Materials and Methods:

Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits.

Statistical Analysis:

Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study.

Results:

Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained.

Conclusions:

Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.     

Preconception care: screening and management of chronic disease and promoting psychological health

Introduction

A large proportion of women around the world suffer from chronic diseases including mental health diseases. In the United States alone, over 12% of women of reproductive age suffer from a chronic medical condition, especially diabetes and hypertension. Chronic diseases significantly increase the odds for poor maternal and newborn outcomes in pregnant women.

Methods

A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for preventing and managing chronic diseases and promoting psychological health on maternal, newborn and child health outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture.

Results

Maternal prepregnancy diabetic care is a significant intervention that reduces the occurrence of congenital malformations by 70% (95% Confidence Interval (CI): 59-78%) and perinatal mortality by 69% (95% CI: 47-81%). Furthermore, preconception management of epilepsy and phenylketonuria are essential and can optimize maternal, fetal and neonatal outcomes if given before conception. Ideally changes in antiepileptic drug therapy should be made at least 6 months before planned conception. Interventions specifically targeting women of reproductive age suffering from a psychiatric condition show that group-counseling and interventions leading to empowerment of women have reported non-significant reduction in depression (economic skill building: Mean Difference (MD) -7.53; 95% CI: -17.24, 2.18; counseling: MD-2.92; 95% CI: -13.17, 7.33).

Conclusion

While prevention and management of the chronic diseases like diabetes and hypertension, through counseling, and other dietary and pharmacological intervention, is important, delivering solutions to prevent and respond to women’s psychological health problems are urgently needed to combat this leading cause of morbidity.

     

Preconception care: caffeine,smoking, alcohol,drugs and other environmental chemical/radiation exposure

Introduction

As providing health education, optimizing nutrition, and managing risk factors can be effective for ensuring a healthy outcome for women and her yet un-conceived baby, external influences play a significant role as well. Alcohol, smoking, caffeine use and other similar lifestyle factors, have now become an integral part of the daily life of most men and women, who use/misuse one or more of these harmful substances regularly despite knowledge of their detrimental effects. The adverse health outcomes of these voluntary and involuntary exposures are of even greater concern in women of child bearing age where the exposure has the potential of inflicting harm to two generations. This paper is examining the available literature for the possible effects of caffeine consumption, smoking, alcohol or exposure to chemicals may have on the maternal, newborn and child health (MNCH).

Methods

A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception usage of caffeine, tobacco, alcohol and other illicit drugs; and exposure to environmental chemicals and radiant on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture.

Results

Heavy maternal preconception caffeine intake of >300mg/d significantly increase the risk of a subsequent fetal loss by 31% (95% CI: 8-58%). On the other hand, preconception alcohol consumption leads to non-significant 30% increase in spontaneous abortion (RR 1.30; 95% CI: 0.85-1.97). Preconception counselling can lead to a significant decrease in the consumption of alcohol during the first trimester (OR 1.79; 95% CI: 1.08-2.97). Periconception smoking, on the other hand, was found to be associated with an almost 3 times increased risk of congenital heart defects (OR 2.80; 95% CI 1.76-4.47). While the review found limited evidence of preconception environmental exposure on maternal, newborn and child health outcomes, occupational exposure in female radiation workers before conception showed an increased impact in risk of early miscarriages.

Conclusion

Identification of substance abuse and environmental history during preconception period provides an opportunity to assist women in reducing major health risks and identify key determinants of healthy pregnancy. Studies have shown that the aversion and prevention of exposure feasibility can play an important role in improving the health of women and their families, however, the results should be interpreted with great caution as there were few studies in each section. Therefore, there is a need for more rigorous studies to test the hypotheses.

     

Patient quality of life and short-term surgical outcomes between robotic and laparoscopic anterior resection for adenocarcinoma of the rectum

Purpose

To compare patient quality of life (QoL) and short-term surgical outcomes between robotic anterior resection (r-AR) and laparoscopic (l-AR) approach.

Methods

Consecutive patients having undergone either robotic or laparoscopic AR for adenocarcinoma were studied. All operations were performed by two surgeons experienced in laparoscopic and recently introduced robotic surgery. Surgical outcomes were determined by post-operative histology and short-term complications. QoL was prospectively assessed using the EORTC QLC-CR30 and QLC-CR29 questionnaires.

Results

In total, 36 patients (18 r-AR) with a median follow-up of 12 months following surgery (9-month robotic and 20-month laparoscopic) were studied. The two groups were similarly matched for age and gender. Laparoscopic patients had a lower ASA grade (p = 0.02). There was no significant difference in surgical outcomes between groups. r-AR patients reported lower pain scales (2 ± 6 vs. 11 ± 13) (p = 0.04), lower levels of insomnia 0 vs. 8 ± 15 (p = 0.04) and a lower abdominal pain scale (2 ± 9 vs. 17 ± 27) (p = 0.04). Male impotence scores were higher in l-AR 33 ± 35 compared to r-AR 7 ± 21 (p = 0.03).

Conclusion

Despite its recent introduction to our centre, the quality of oncological resection using the robotic surgery is comparable to laparoscopy. Lower impotence and QoL scores in patients after robotic procedure may be explained on the basis of better visualisation and precise tissue handling.

     

The Rise of Electronic Health Record Adoption Among Family Physicians

PURPOSE

Realizing the benefits of adopting electronic health records (EHRs) in large measure depends heavily on clinicians and providers’ uptake and meaningful use of the technology. This study examines EHR adoption among family physicians using 2 different data sources, compares family physicians with other office-based medical specialists, assesses variation in EHR adoption among family physicians across states, and shows the possibility for data sharing among various medical boards and federal agencies in monitoring and guiding EHR adoption.

METHOD

We undertook a secondary analysis of American Board of Family Medicine (ABFM) administrative data (2005–2011) and data from the National Ambulatory Medical Care Survey (NAMCS) (2001–2011).

RESULTS

The EHR adoption rate by family physicians reached 68% nationally in 2011. NAMCS family physician adoption rates and ABFM adoption rates (2005–2011) were similar. Family physicians are adopting EHRs at a higher rate than other office-based physicians as a group; however, significant state-level variation exists, indicating geographical gaps in EHR adoption.

CONCLUSION

Two independent data sets yielded convergent results, showing that adoption of EHRs by family physicians has doubled since 2005, exceeds other office-based physicians as a group, and is likely to surpass 80% by 2013. Adoption varies at a state level. Further monitoring of trends in EHR adoption and characterizing their capacities are important to achieve comprehensive data exchange necessary for better, affordable health care.