Occurrence of a mosquito vector in bird houses: Developmental consequences and potential epidemiological implications

Even with continuous vector control, dengue is still a growing threat to public health in Southeast Asia. Main causes comprise difficulties in identifying productive breeding sites and inappropriate targeted chemical interventions. In this region, rural families keep live birds in backyards and dengue mosquitoes have been reported in containers in the cages. To focus on this particular breeding site, we examined the capacity of bird fecal matter (BFM) from the spotted dove, to support Aedes albopictus larval growth. The impact of BFM larval uptake on some adult fitness traits influencing vectorial capacity was also investigated. In serial bioassays involving a high and low larval density (HD and LD), BFM and larval standard food (LSF) affected differently larval development. At HD, development was longer in the BFM environment. There were no appreciable mortality differences between the two treatments, which resulted in similar pupation and adult emergence successes. BFM treatment produced a better gender balance. There were comparable levels of blood uptake and egg production in BFM and LSF females at LD; that was not the case for the HD one, which resulted in bigger adults. BFM and LSF females displayed equivalent lifespans; in males, this parameter was shorter in those derived from the BFM/LD treatment. Taken together these results suggest that bird defecations successfully support the development of Ae. albopictus. Due to their cryptic aspects, containers used to supply water to encaged birds may not have been targeted by chemical interventions.     

Gene expression of IQGAPs and Ras families in an experimental mouse model for hepatocellular carcinoma: a mechanistic study of cancer progression

IQGAPs genes play critical role in either induction or suppression of cancer and its progression, however the relationship between Ras genes and these genes are still unclear. In this study, we tried to understand the mechanistic action of IQGAPs genes and its correlation with Ras genes in mouse hepatic cancer model. The genetic expressions of IQGAP1, IQGAP2, IQGAP3, Hras, Kras, Nras, Mras, Caspase3, and BAX were followed in both hepatocellular carcinoma and normal liver cells of Balbc mice. Genotoxic agent diethylnitrosamine (DEN)-induced hepatic cancer model was induced in male mice and recorded the occurrence of hepatocellular carcinoma by morphological and histological changes in the liver. It was observed that mRNA expressions of IQGAP1, Hras, Kras, Nras, Mras, Caspase3, and BAX genes were highly elevated in hepatocellular carcinoma cells when compared with normal liver cells, additionally their expressions increased by concentrating the dose of DEN. While, the expressions of IQGAP2 and IQGAP3 were significantly decreased in hepatocellular carcinoma cells when compared with normal liver cells, as well as their expressions decreased more with increasing the dose of DEN. It was concluded from this study that IQGAP1 has a strong signaling relationship with Ras genes in induction of cancer and it is considered as a key gene for induction or suppression of the hepatocellular carcinoma.     

Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC_0–24,ss), the steady-state maximum concentration of the drug in plasma (C_max,ss), and the steady-state concentration of the drug in plasma at 24 h (C_24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01637922","term_id":"NCT01637922"}}NCT01637922.)     

A highly sensitive fluorimetric protocol based on isoindole formation for determination of gabapentin

A new, simple, highly sensitive and selective spectrofluorimetric method was developed for determination of gabapentin through its derivatization with o-phthalaldehyde in the presence of 2-mercaptoethanol. The resulting product was highly fluorescent and its emission intensity was measured at 431 nm after excitation at 335 nm. The effect of different experimental parameters on the formation and stability of the fluorescent product was carefully studied and optimized. The fluorescence–concentration plot was rectilinear over the range of 25–125 ng mL⁻¹. The lower detection and quantification limits were 3.4 mL⁻¹ and 11.2 ng mL⁻¹, respectively. The procedure was fully validated according to the guidelines of the International Conference on Harmonization. The proposed method was successfully applied for the determination of the investigated drug in its pharmaceutical capsules and the results were in agreement with those of the reported method, in terms of the accuracy and precision. The low cost of analysis and high sensitivity make the proposed method ideally suited for analysis of the investigated drug in quality control laboratories.

A new, simple, highly sensitive and selective spectrofluorimetric method was developed for determination of gabapentin through its derivatization with o-phthalaldehyde in the presence of 2-mercaptoethanol.     

Doxycycline‐Loaded β‐Tricalcium Phosphate Release Following EDTA Root Surface Etching Improved the Clinical Outcomes in Chronic Periodontitis: An In Vivo Study

Background: The main objective of the present study is to quantify doxycycline (DOX) release from β‐tricalcium phosphate (β‐TCP) after EDTA root surface treatment. Methods: Thirty systemically healthy patients with ≥1 paired contralateral interproximal intrabony defect ≥4 mm deep along with an interproximal probing depth ≥6 mm and clinical attachment level ≥4 mm were randomized into two groups. Group 1 (G1) consisted of sites treated with open flap debridement followed by placement of DOX blended with β‐TCP (DOX‐β‐TCP), whereas group 2 (G2) sites were treated with flap surgery followed by the placement of DOX blended with β‐TCP after EDTA etching of the exposed root surfaces (DOX‐β‐TCP + EDTA). Samples of gingival crevicular fluid (GCF) were obtained 1, 3, 7, 14, and 21 days after surgery. Quantitative measurements of DOX were taken with high‐performance liquid chromatography. Clinical evaluation and follow‐up for 6 months were performed. Results: At 21 days, the DOX‐β‐TCP + EDTA–treated group showed a 194.7 µg/mL value. The DOX‐β‐TCP + EDTA–treated group retained more DOX during the periods of 3, 7, 10, 14, and 21 days than the DOX‐β‐TCP–treated group. Six months after therapy, DOX‐β‐TCP + EDTA–treated sites showed more significant clinical improvements compared to DOX‐β‐TCP–treated sites (P ≤ 0.05). Conclusions: EDTA root surface etching enhances DOX availability in the GCF following its release from β‐TCP as a drug carrier.     

Obstructive sleep apnea and diabetic neuropathy: a novel association in patients with type 2 diabetes

Rationale: Diabetic peripheral neuropathy is common and causes significant morbidity. Obstructive sleep apnea (OSA) is also common in patients with type 2 diabetes. Because OSA is associated with inflammation and oxidative stress, we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes. Objectives: To assess the relationship between OSA and peripheral neuropathy in patients with type 2 diabetes. Methods: A cross-sectional study of adults with type 2 diabetes recruited randomly from the diabetes clinic of two UK hospitals. Measurements and Main Results: Peripheral neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument. OSA (apnea-hypopnea index ≥ 5 events/h) was assessed using home-based, multichannel respiratory monitoring. Serum nitrotyrosine was measured by ELISA, lipid peroxide by spectrophotometer, and microvascular function by laser speckle contrast imaging. Two hundred thirty-four patients (mean [SD] age, 57 [12] yr) were analyzed. OSA prevalence was 65% (median apnea-hypopnea index, 7.2; range, 0-93), 40% of which were moderate to severe. Neuropathy prevalence was higher in patients with OSA than those without (60% vs. 27%, P < 0.001). After adjustment for possible confounders, OSA remained independently associated with diabetic neuropathy (odds ratio, 2.82; 95% confidence interval, 1.44-5.52; P = 0.0034). Nitrotyrosine and lipid peroxide levels (n = 102, 74 with OSA) were higher in OSA and correlated with hypoxemia severity. Cutaneous microvascular function (n = 71, 47 with OSA) was impaired in OSA. Conclusions: We describe a novel independent association between diabetic peripheral neuropathy and OSA. We identified increased nitrosative/oxidative stress and impaired microvascular regulation as potential mechanisms. Prospective and interventional studies are needed to assess the impact of OSA and its treatment on peripheral neuropathy development and progression in patients with type 2 diabetes.     

Cultural adaptation and validation of the “Kidney Disease and Quality of Life - Short Form (KDQOL-SF™) version 1.3” questionnaire in Egypt

Background

Health Related Quality of Life (HRQOL) instruments need disease and country specific validation. In Arab countries, there is no specific validated questionnaire for assessment of HRQOL in chronic kidney disease (CKD) patients. The aim of this study was to present an Arabic translation, adaptation, and the subsequent validation of the kidney disease quality of life-short form (KDQOL-SF^TM) version 1.3 questionnaire in a representative series of Egyptian CKD patients.

Methods

KDQOL-SF^TM version 1.3 was translated into Arabic by two independent translators, and then subsequently translated back into English. After translation disparities were reconciled, the final Arabic questionnaire was tested by interviewing 100 pre-dialysis CKD (stage 1-4) patients randomly selected from outpatients attending the Nephrology clinic at the Main Alexandria University Hospital. Test re-test reliability was performed, with a subsample of 50 consecutive CKD patients, by two interviews 7 days apart and internal consistency estimated by Cronbach’s α. Discriminant, concept, and construct validity were assessed.

Results

All items of SF-36 met the criterion for internal consistency and were reproducible. Of the 10 kidney disease targeted scales, only three had Cronbach’s α <0.7: quality of social interaction (0.23), work status (0.28), and cognitive function (0.60). All disease specific scales were reproducible. Results from discriminant validity showed that the study questionnaire could discriminate between patients’ subgroups. As for concept validity, the correlation between all domains of the questionnaire with overall health ratewas significant for all domains except for the work status, sexual function, emotional wellbeing, and role emotional. Furthermore, the correlation between the disease specific domains and the two composite summaries of SF-36 (physical and mental composite summaries) was significant for all domains except for sexual function with mental composite summary. Construct validity was indicated by the observation that the majority of the domains of the kidney disease targeted scale of KDQOL-SF^TM 1.3 were significantly inter-correlated. Finally, principal component analysis of the kidney disease targeted scale indicated that this part of the questionnaire could be summarized into 10 factors that together explained 70.9% of the variance.

Conclusion

The results suggest that this Arabic version of the KDQOL-SF^TM 1.3 questionnaire is a valid and reliable tool for use in Egyptian patients with CKD.

     

Chemisorption and sustained release of cefotaxime between a layered double hydroxide and polyvinyl alcohol nanofibers for enhanced efficacy against second degree burn wound infection

Zn–Al layered double hydroxides (LDHs) were synthesized by a chemical method, while polyvinyl alcohol (PVA) nanofibers were fabricated by an electrospinning approach; we also synthesized Zn–Al LDH/cefotaxime (cefotax), Zn–Al LDH@PVA, and Zn–Al LDH/cefotax@PVA (LCP). Characterizations were performed by X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, Brunauer–Emmett–Teller analysis, thermogravimetric-differential thermal analysis techniques, dynamic light scattering, X ray-florescence, and carbon, hydrogen, and nitrogen (CHN) analyses. The adsorption isotherm of cefotax and its entrapment percentage, release, and kinetics were also investigated. The results confirmed the elemental constituents of the mentioned formulas, which exhibited different degrees of crystallinity and different morphologies. Besides, these formulas were tested in vitro as antimicrobial agents and applied in vivo against second-degree wound burns induced in rats'' skin. The adsorption of cefotax occurred chemically, and the experimental data were fitted with different isotherm models, where the Freundlich and Toth models gave the best fits. The entrapment percentage in LDH/cefotax was 77.41% and in LDH/cefotax@PVA, it was 67.83%. The sustained release of cefotax from LDH and LCP was attainable; the release percentages were 89.31% and 81.55% in up to 12 h, respectively. The release kinetics of cefotax from LDH fitted well with first-order kinetics, while that for LCP was parabolic. The formulas showed uneven antimicrobial effects against Gram-positive and Gram-negative bacteria; the best effect was exhibited by Zn–Al LDH/cefotax@PVA due to its sustained release. Finally, investigating the possibility of using these formulas in the clinical setting should be considered.

This study succeeded to formulate, characterize, and investigate cefotax release and kinetics, and to compare cetofax with other known antibacterial agents.