Effect of ultra violet (UV-C) and cold storage on orange juice quality.

The effect of the UV-C treatment on the physico-chemical characteristics, pectin methylesterase activity (PME) as well as microbial quality of orange juice, compared to fresh juice, was studied. The juice samples were UV-C (254 nm) irradiated for different exposure times (15, 30, 45 and 60 min) and stored at 4 ± 1 °C for 30 days. UV-C treatment didn't significantly (p ≤ 0.05) affect pH values, titratable acidity, TSS (%), ascorbic acid content and PME activity in both fresh and stored samples. Increasing the exposure time from 5 to 60 min. showed no significant effect (p ≤ 0.05) on L* and a* values for both the fresh and the stored samples. On the contrary, negative relationship was observed between UV-C exposure time and b* values. Total bacterial counts were significantly (p ≤ 0.05) reduced from 2.69 to 0.93 log10 CFU/mL when the exposure time was increased from 0 to 60 min. The UV-C treatment showed similar trend on yeast and mold counts but to a lesser extend due to their resistance to UV. The sensory characteristics, i.e. odour, colour, taste, consistency and overall acceptability didn't change (p ≤ 0.05) as a result of UV-C treatment at any tested exposure times.

HPLC Determination of Fexofenadine in Human Plasma For Therapeutic Drug Monitoring and Pharmacokinetic Studies.

A simple and sensitive method was developed for fexofenadine determination in human plasma by liquid chromatography with ultraviolet detection. Satisfactory separation was achieved on a Hypersil® BDS C18 column (250 × 4.6 mm, 5µm) using a mobile phase comprising 20 mm sodium dihydrogen phosphate-2 hydrate (pH adjusted to 3 with phosphoric acid)-acetonitrile at a ratio of 52:48, v/v. The elution was isocratic at ambient temperature with a flow rate of 1.0 mL/min. The UV detector was set at 215 nm for the drug and 330 nm for the internal standared (tinidazole). The total time for a chromatographic separation was ~6.5 min. Linearity was demonstrated over the concentration range 0.01-4 µg/mL. The observed within- and between-day assay precision ranged from 0.346 to 13.6%; accuracy varied between 100.4 and 111.2%. This method was successfully applied for therapeutic drug monitoring in patients treated with clinical doses of fexofenadine and for pharmacokinetic studies. Copyright © 2015 John Wiley & Sons, Ltd.

Simultaneous determination of paracetamol and methocarbamol in human plasma By HPLC using UV detection with time programming: application to pharmacokinetic study.

BACKGROUND: A combination of methocarbamol (MET) and paracetamol (PAR) is a widely used treatment approach. It provides complementary modes of action for treatment of pain associated with muscle spasm. The aim of this work was to develop and validate a new sensitive and reproducible isocratic reversed phase HPLC-UV detection method for simultaneous determination of MET and PAR in human plasma for the routine use in a therapeutic drug monitoring and pharmacokinetic laboratories. METHODS: A simple HPLC assay was developed and validated for the simultaneous determination of the above-mentioned drugs in small samples of human plasma (0.25 mL). After protein precipitation with methanol, satisfactory separation was achieved on a Hypersil® BDS C18 column (250 mm × 4.6 mm, 5 µm) using a mobile phase comprising 20 mM sodium dihydrogen phosphate buffer (pH=3) and methanol at a ratio of 80:20, v/v; the elution was isocratic at ambient temperature with a flow rate of 1.2 ml/min. The UV detector was programmed at 254 nm for 7.0 min to measure PAR and IS and at 272 nm for the subsequent 3 min to measure MET. RESULTS: Linearity was demonstrated over the concentration range from 0.02 to 20 µg/ml (mean R(2) = 0.9998, n = 10). The observed within- and between-day assay precision ranged from 1.11 to 9.4 and 2.46 to 10.0% for PAR and MET, respectively; whereas, accuracy varied between 95.2-101% and 93.9-102.2% for PAR and MET, respectively. Mean drug recovery was 99.8 for PAR and 99.0% for MET. PAR and MET were stable in frozen plasma over a period of 3 months at -80 °C. CONCLUSIONS: The validated method was applied successfully to a bioequivalence study of PAR/MET (500/400 mg) fixed dose combination tablet in healthy volunteers (n=24).

Pharmacokinetics and relative bioavailability evaluation of linezolid suspension and tablet formulations.

The oral liquid formulations poses an alternative way in providing medications to pediatric patients, geriatric patients, patients with feeding tubes, and patients who cannot swallow solid dosage forms. This study was conducted to evaluate the pharmacokinetics (PKs) and relative bioavailability of suspension (reference) and tablet (test) formulations of Linezolid (LZD). In vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2 Way, Cross-Over Study with a washout period of 1-week. Under fasting conditions, 28 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either 30 ml LZD or 1 tablet (600 mg LZD) of marketed suspension and tablet formulations. Plasma samples were obtained over a 48-h interval and analyzed for LZD by reversed phase liquid chromatography with ultraviolet detection. The 90% confidence intervals for the ratio of log transformed values of Cmax, AUC0-t, and AUCt-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, in this small study in healthy Egyptian adult male volunteers, a single 600 mg dose of the tablet formulation demonstrated comparable rate and extent of absorption to a single 600 mg dose of the suspension formulation based on the US FDA's regulatory definition. No adverse events occurred or were reported after a single 600 mg LZD and both formulations were well tolerated.

Effect of the formulation on the bioequivalence of meloxicam: tablet and suspension.

Meloxicam is a non-steroidal anti-inflammatory drug of the enolic acid class that preferentially inhibits cyclooxygenase-2 imparting analgesic, antipyretic and anti-inflammatory effects. This study was conducted to evaluate the effect of formulation on the pharmacokinetics (PK) and comparative bioavailability of suspension (reference) and tablet (test) formulations of meloxicam. In this in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2 way, cross-over study with a washout period of 2 weeks. Under fasting conditions, 24 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of 15 mg meloxicam either as 10 mL of a marketed suspension or one tablet. Plasma samples were obtained over a 96-h interval and analyzed for meloxicam by reversed phase liquid chromatography with ultraviolet detection. A non-compartmental model was used to determine the PK parameters of meloxicam. The 90% confidence intervals for the ratio of log transformed values of Cmax, AUC0-t, and AUCt-∞ of the 2 treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, in this small study in healthy Egyptian adult male volunteers, a single 15 mg dose of the tablet formulation was bioequivalent to a single 15 mg dose of the suspension formulation with no significant effect of formulation based on the US FDA's regulatory definition. No adverse events occurred or were reported during the study and both formulations were well tolerated.

Comparative in vitro dissolution and in vivo bioavailability of diflunisal/naproxen fixed-dose combination tablets and concomitant administration of diflunisal and naproxen in healthy adult subjects.

A simple validated high-performance liquid chromatography (HPLC) assay was developed for determination of diflunisal and naproxen in human plasma samples. This is to compare the bioavailability of diflunisal-naproxen fixed-dose combination (FDC) with their separate dosage forms. The in vitro dissolution study was adopted to compare the dissolution behavior of FDC with respect to separate marketed tablets. In vivo study was conducted according to a single-center, randomized, single-dose, laboratory-blinded, 2 Way, Cross-Over Study with a washout period of 10 days. Under fasting conditions, 24 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either one FDC tablet or co-administration of two separate diflunisal and naproxen marketed tablets. Plasma samples were obtained over a 72-h interval and analyzed for diflunisal and naproxen by reversed phase liquid chromatography with UV detection. The pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞, tmax, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax, AUC0-t, and AUCt-∞ of the 2 treatments were within the acceptable range (0.8-1.25) for bioequivalence. From pharmacokinetic and in vitro studies perspectives, 1 FDC tablet demonstrated similar relative bioavailability with the 2 individual -reference tablets.

The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients.

Both propofol and midazolam are known to inhibit immune function. The aim of this study was to investigate cytokine production in critically ill surgical patients as early markers of immune response to prolonged infusion of propofol and midazolam. The study enrolled 40 elective patients who were to receive long-term sedation for more than 2 days. Patients were randomly allocated to one of two equally sized groups. Central venous blood samples for measurement of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were drawn prior to the start and after 48 h of infusion. After 48 h, propofol caused significant increases in IL-1beta (24%), IL-6 (23%) and TNF-alpha (4.8 times) levels, while midazolam caused significant decreases in IL-1beta (21%), IL-6 (21%) and TNF-alpha (19%). Both agents caused significant decreases in IL-8 levels (propofol: 30%, midazolam: 48%, p < 0.05). Propofol caused significant decreases in IL-2 levels (68%, p < 0.001) but increases in IFN-gamma (30%, p < 0.05), whereas there was no significant change with midazolam compared with the pre-infusion level. In conclusion, during 48 h of continuous infusion, propofol stimulated, while midazolam suppressed, the production of the pro-inflammatory cytokines IL-1beta, IL-6 and TNF-alpha, and both caused suppression of IL-8 production. Propofol inhibited IL-2 production and stimulated IFN-gamma production, whereas midazolam failed to do so. Therefore, sedative agents may have clinical implications in high-risk and immunocompromised patients.

The effect of the preemptive use of the NMDA receptor antagonist dextromethorphan on postoperative analgesic requirements.

UNLABELLED: Both central sensitization after peripheral tissue injury and the development of opiate tolerance involve activation of N-methyl-D-aspartate receptors. In this double-blinded, randomized study, we investigated the preemptive versus postincisional effects of dextromethorphan, an N-methyl-D-aspartate receptor antagonist, on postoperative pain management. Sixty ASA I and II patients undergoing elective upper abdominal surgery were randomly allocated to three equally sized groups. The Preincisional group patients received dextromethorphan (120 mg) IM 30 min before skin incision and a placebo (isotonic saline) 30 min before the end of surgery. The Postincisional group received the same dose of dextromethorphan 30 min before the end of surgery and a placebo 30 min before skin incision, and the Control group received a placebo both 30 min before skin incision and 30 min before the end of surgery. A standard general anesthetic technique including fentanyl, propofol, isoflurane, and atracurium was used. Postoperative meperidine patient-controlled analgesia (PCA) was used. There were no significant group differences in the median pain scores except in the visual analog scale at 6 h both at rest and on movement; these were significantly lower in the Preincisional group than the other two groups (P < 0.05). The mean time to initiation of PCA was significantly longer in the Preincisional than in the Postincisional and Control groups (mean [SD]: 10.7 [2.2 h], 5.4 [2.1 h], and 3.7 [1.6 h], respectively; P < 0.001]. The 24-h PCA-meperidine consumption was significantly less in the Preincisional than in the Postincisional and Control groups (mean [SD]: 140 [60 mg], 390 [80 mg], and 570 [70 mg], respectively; P < 0.001]. The incidence of postoperative hypoxemia (SpO(2) < 90%) and nausea was significantly less in the Preincisional group (P < 0.05). In conclusion, preincisional IM 120 mg dextromethorphan compared with the same postincisional dose significantly reduced postoperative meperidine consumption. IMPLICATIONS: IM administration of preincisional dextromethorphan (120 mg), allowing the use of a larger dose sufficient to block the central sensitization caused by activation of the N-methyl-D-aspartate receptors, provides preemptive analgesia and has a supportive role in postoperative pain relief, as shown by a significant decrease in 24-h meperidine consumption.

The effect of halothane and isoflurane on plasma cytokine levels.

The aim of this study was to investigate the effect of halothane vs. isoflurane on cytokine production during minor elective surgery. Forty adult patients, ASA I-II were randomly allocated to receive halothane or isoflurane. Venous samples for interleukin (IL)-1beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were taken before anaesthesia, before incision, at the end of anaesthesia and 24 h postoperatively. In both groups, IL-6 and TNF-alpha levels remained low throughout the study period. Before incision, in both groups IL-1beta and IFN-gamma showed a decrease (p<0.01 for IL-1beta in isoflurane group and p<0.05 for the others) compared with pre-induction. By the end of anaesthesia and surgery, IL-1beta had increased significantly (p<0.05) and IFN-gamma had decreased significantly (p<0.05) in both groups compared with pre-incisional levels. By 24 h postoperatively in both groups, IL-1beta had decreased significantly (p<0.05), whereas IFN-gamma had increased significantly (p<0.05) compared with the end of anaesthesia and surgery level. Pre-incisionally, IL-2 increased in the halothane group (p<0.01), whereas it decreased significantly in the isoflurane group (p<0.001) compared with the pre-induction level. By the end of anaesthesia and surgery and by 24 h postoperatively, IL-2 had decreased significantly in the halothane group (p<0.001), whereas it increased significantly in the isoflurane group (p<0.001) compared with pre-incision and end of anaesthesia and surgery levels, respectively.

The effect of anaesthesia and surgery on plasma cytokine production.

The aim of this study was to investigate cytokine production in response to anaesthesia [total intravenous anaesthesia (TIVA) with propofol, sufentanil and atracurium] and surgery (laparoscopic vs. open cholecystectomy). Forty adult patients, ASA I-II, undergoing elective laparoscopic (group 1) or open (group 2) cholecystectomy were studied. Venous blood samples for measurement of interleukin (IL)-1beta, IL-2, IL-4, IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were taken before the induction of anaesthesia, pre-incisionaly, at the end of anaesthesia and surgery and 24-h postoperatively. Pre-incisionaly, in both groups, IL-1beta, IL-4, IL-6, TNF-alpha and IFN-gamma did not show a significant change, whereas IL-2 showed a significant decrease (p < 0.005 in group 1 and p < 0.001 in group 2) compared with pre-induction levels. By the end of anaesthesia and surgery, IL-1beta, IL-2, IL-4, IL-6 and TNF-alpha showed a significant increase in group 2 (p < 0.005 for IL-1beta, IL-2 and IL-4, and p < 0.05 for IL-6 and TNF-alpha); while in group 1, only IL-2 showed a significant increase (p < 0.01) and IFN-gamma showed a significant decrease (p < 0.05) compared with pre-incisional levels. By 24-h postoperatively, IL-1beta, IL-4, IL-6 and TNF-alpha had decreased significantly in group 2 (p < 0.005 for IL-4 and p < 0.05 for the others); whereas in group 1, IL-2 and IFN-gamma showed a significant increase (p < 0.005) compared with the end of anaesthesia and surgery level. In conclusion, TIVA with propofol, sufentanil and atracurium does not seem to have a significant effect on IL-1beta, IL-4, IL-6, TNF-alpha and IFN-gamma release. IL-2 was the only cytokine to show a significant decrease due to the effect of anaesthesia alone in both groups. The cytokine response to open cholecystectomy stimulated both the pro-inflammatory (IL-1beta, IL-6 and TNF-alpha) and the anti-inflammatory (IL-4) components, while this response was absent in laparoscopic cholecystectomy.

Prophylactic anti-emetic efficacy of ondansetron in laparoscopic cholecystectomy under total intravenous anaesthesia. A randomised, double-blind comparison with droperidol, metoclopramide and placebo.

The prophylactic anti-emetic efficacy and safety of pre-operative intravenous ondansetron was evaluated in a randomised, double-blind, comparison with droperidol, metoclopramide and placebo in 160 ASA grade 1 and 2 patients undergoing laparoscopic cholecystectomy under total intravenous anaesthesia. The patients were randomly allocated to receive ondansetron (4 mg), droperidol (1.25 mg), metoclopramide (10 mg) or placebo given as a single intravenous dose immediately before induction of a standardised general anaesthetic. There were no significant differences between the four study groups with regard to the demographic and anaesthetic data, postoperative analgesia, postoperative sedation scores, duration of postoperative hospital stay and incidence of adverse events. The incidence of nausea and vomiting was significantly lower (p < 0.05) between 1 h and 4 h after surgery in the ondansetron group compared with the droperidol, metoclopramide and placebo groups. The incidence of nausea was similar in the four groups in the other study periods: 0-1 h and 4-24 h. The incidence of vomiting was lower in the ondansetron, droperidol and metoclopramide groups than in the placebo group between 1 and 4 h but was the same between 4 and 24 h. As a result of the lower incidence of nausea and vomiting between 1 h and 4 h in the ondansetron group, the overall incidence of nausea and vomiting was lower during the first 24 h after surgery in this group than in the other three groups.

New autosomal recessive multiple congenital abnormalities/mental retardation syndrome with craniofacial dysmorphism absent corpus callosum, iris colobomas and connective tissue dysplasia.

We report three sibs, one boy and two girls, with a similar MCA/MR syndrome, where parents were first cousins. They had macrodolichocephaly, an elongated face, apparently low-set simple ears, hypertelorism, bilateral "key-hole' colobomata of the iris, retina and choroid, a beaked nose, micrognathia and dental anomalies. Brain CT scan showed dilated ventricles and an absent corpus callosum. Skeletal anomalies included brachydactyly of the hands and feet, genua vara and flat feet. Two sibs had left ventricular enlargement, and aortic dilatation and regurgitation. Review of the literature from the London Dysmorphology Data Base (LDDB) and OMIM suggests that this family represents a new syndrome.

Photorefractive keratectomy and laser in situ keratomileusis for myopia between 6.00 and 10.00 diopters.

BACKGROUND: Excimer laser photorefractive keratectomy (PRK) can be effective in correcting myopia up to -6.00 diopters (D). Between -6.00 D and -10.00 D, the procedure is considered less effective and safe because it has been associated with dense scar formation and a high rate of regression. We compared photorefractive keratectomy (PRK) in this group of myopes with excimer laser keratomileusis in situ (LASIK). METHODS: Forty consecutive eyes with a manifest refraction between -6.00 and -10.00 D were treated with PRK using an ablation-zone diameter of 6 mm. Subsequently, 40 consecutive eyes were treated with LASIK under a hinged flap using an ablation-zone diameter of 5 mm. All procedures used a Summit OmniMed laser and were done by the same surgeon. RESULTS: Preoperatively, 24 eyes (60%) undergoing PRK had 20/20 spectacle-corrected visual acuity; 1 year postoperatively, 20 (50%) had 20/20 vision uncorrected. Preoperatively, 13 eyes (33%) undergoing LASIK had 20/20 spectacle-corrected visual acuity; 1 year postoperatively, 24 (60%) could see 20/20 uncorrected. Sixteen (39%) PRK eyes had a spherical equivalent refraction within +/-1.00 D at 1 year; 20 (60%) eyes undergoing LASIK had a refraction within +/-1.00 D at that point. None of the eyes treated with LASIK developed corneal haze, while after PRK, 36 eyes (90%) developed haze (23 eyes [57%] +2 to +3). CONCLUSION: LASIK under a hinged flap proved superior to PRK in treating myopia between -6.00 D and -10.00 D.