Optimization and evaluation of venlafaxine hydrochloride fast dissolving oral films

Three factors, three levels (3³) full factorial design was used to develop venlafaxine HCl fast dissolving oral films (FDOFs) to optimize the concentrations of the film forming polymer; hydroxypropyl methylcellulose HPMC (X1), superdisintegrant; sodium starch glycolate SSG, (X2) and glycerol as the film plasticizer (X3). Effects of the three factors on the disintegration time (Y1), swelling index (Y2), and dissolution efficiency at 15 min; DE%15 (Y3) of the prepared FDOFs were evaluated by using statistical models. The optimized film formula was characterized in term of x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and morphological characteristics.Disintegration time was found to increase with the increase in HPMC (X1) concentration, and the shortest disintegration time (21.67 ± 2.08 s) was observed in case of F2 formula (lowest HPMC level and highest glycerol level in absence of SSG). The highest swelling index (3.64 ± 0.59) was observed in case of film formula F1 (medium concentrations of both HPMC and glycerol and highest SSG concentration. The results also indicated that as the concentration of HPMC increased the DE%15 decreased. SSG (X2), with highest value (72.33 ± 1.71%) was recorded for in case of F12 (using 2% HPMC, 5%SSG and 1.5% glycerol). The optimized FDOF formula derived by the statistical models suggested 2% HPMC, 5% SSG, and 1% glycerol.The data obtained from DSC and XRPD revealed no interaction between drug and FDOT excipients. In addition, XRPD studies proved that the venlafaxine HCl was homogeneously dispersed in the film matrix.     

Thoracoscopic sympathectomy: endobronchial anesthesia vs endotracheal anesthesia with intrathoracic CO2 insufflation

Purpose. To compare clinical advantages and hemodynamic and respiratory changes during one lung-collapsed ventilation (OLCV) using a double-lumen tube (DLT) or a single-lumen tube (SLT) with intrathoracic CO₂ insufflation, in patients undergoing thoracic sympathectomy (TS) under general anesthesia. Methods. One hundred and twenty-five patients (94 men and 31 women) undergoing TS for the treatment of palmar hyperhidrosis (PH) were randomly allocated to two groups: group A (68 patients; age, 29 ± 6 years) in whom DLT was used, and group B (57 patients; age, 32 ± 3 years) in whom SLT with intrathoracic CO₂ insufflation at a rate of 0.5–1 l·min⁻¹ and sustained intrathoracic pressure at 6 mmHg insufflation were used. Anesthesia was maintained with 1 minimum alveolar concentration (MAC) isoflurane in 50% nitrous oxide in oxygen with incremental doses of sufentanil and atracurium when required. Arterial blood gases were measured in 10 patients in group B. Hemodynamic and respiratory parameters were obtained perioperatively. Results. There were no significant differences in hemodynamic and respiratory parameters between the two groups during the study phases, except for the arterial oxygen saturation (SpO₂). The times required for anesthesia and surgery were significantly shorter in the SLT group than in the DLT group. SpO₂ during OLCV was 95 ± 1% with DLT and 98 ± 1% with SLT, with a significant difference. Three patients had an SpO₂ of less than 90% in the recovery room, where the chest tube position was readjusted, with no further sequelae. Conclusion. General anesthesia with SLT and intrathoracic CO₂ insufflation provides optimal operating conditions, adequate oxygenation, and perfect hemodynamic stability during TS. Received: November 28, 2000 / Accepted: August 8, 2001     

Impedance Cardiography: Noninvasive Assessment of Hemodynamics and Thoracic Fluid Content During Bariatric Surgery

Background: The effects of pneumoperitoneum (ppm) on hemodynamic parameters during bariatric surgery were investigated using the impedance cardiography monitor. Methods: 11 patients with BMI 46.5±10 kg/m² (range 38.9-60.8 kg/m²) underwent laparoscopic adjustable gastric banding under general anesthesia. Besides routine monitoring, the impedance cardiography (ICG) monitor was used to monitor cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), and thoracic fluid content (TFC). Data were recorded at three stages: A) before ppm, B) during ppm, and C) after gas deflation. One-way analysis of variance (ANOVA) was used to analyze differences of the data before, during and after ppm, and post-hoc (Bonferoni test) for multiple comparisons of the data obtained. For all comparisons, P<0.05 was considered significant. Results: There were significant low mean values of heart rate (HR), CO and CI at stage B compared to stage A (P<0.05). The mean values of TFC at stages A, B, and C were 30.48 ± 4.69, 29.74 ± 2.86 and 31.72 ± 4.93 k/Ohm respectively, with a non-significant relationship (P>0.05). The mean values of SVR during the same stages A, B and C were 1299.18 ± 374.40, 1873.64 ± 276.26 and 1669.36 ± 537.92 dynes sec cm^-5 respectively, with significant high mean values at stages B and C compared to mean value at stage A (P<0.05). Conclusions: Morbid obesity and pneumoperitoneum have significant effects on hemodynamics. However, it appears that these changes were of marginal clinical significance.     

Synthesis and Pharmacological Characterization of a Novel Sigma Receptor Ligand with Improved Metabolic Stability and Antagonistic Effects Against Methamphetamine

Methamphetamine interacts with sigma receptors at physiologically relevant concentrations suggesting a potential site for pharmacologic intervention. In the present study, a previous sigma receptor ligand, CM156, was optimized for metabolic stability, and the lead analog was evaluated against the behavioral effects of methamphetamine. Radioligand binding studies demonstrated that the lead analog, AZ66, displayed high nanomolar affinity for both sigma-1 and sigma-2 receptors (2.4 ± 0.63 and 0.51 ± 0.15, respectively). In addition, AZ66 had preferential affinity for sigma receptors compared to seven other sites and a significantly longer half-life than its predecessor, CM156, in vitro and in vivo. Pretreatment of male, Swiss Webster mice with intraperitoneal (10-20 mg/kg) or oral (20-30 mg/kg) dosing of AZ66 significantly attenuated the acute locomotor stimulatory effects of methamphetamine. Additionally, AZ66 (10-20 mg/kg, i.p.) significantly reduced the expression and development of behavioral sensitization induced by repeated methamphetamine administration. Taken together, these data indicate that sigma receptors can be targeted to mitigate the acute and subchronic behavioral effects of methamphetamine and AZ66 represents a viable lead compound in the development of novel therapeutics against methamphetamine-induced behaviors.     

Anesthetic management of a patient with myotonic dystrophy for laparoscopic cholecystectomy--a case report

Myotonic dystrophy (MD) is rare disease that offers challenges to anesthesiologists. We report a case of adult patient with myotonic dystrophy who underwent laparoscopic cholecystectomy. A 48-year-old male patient, known case of MD, was presented for laparoscopic cholecystectomy. Physical examination revealed, young man, calm, quite, cooperative, not in pain or distress with frontal baldness, temporal bone recession, elongated face, mild degree of ptosis and swan neck. Under complete aseptic conditions, thoracic epidural T6-7 with catheter insertion was performed while the patient was placed on left lateral side. Plain bupivacaine 0.5% 7cc was injected through the catheter. Level of analgesia tested with ice reached up to T4. Intravenous sedation was achieved with midazolam 2 mg and ketamine 50 mg. The patient was comfortably lying supine on warm heated mattress, except of bilateral shoulder pains which was relieved with midazolam and ketamine. In conclusion, regional anesthesia, spinal or epidural, is preferable in MD patients. Shoulder pains is the main intraoperative problem encountered in our patient. Therefore, studies are needed for treating shoulder pain. To the best of our knowledge, this is the first case report in a patient with MD who underwent laparoscopic cholecystectomy under thoracic epidural analgesia. Myotonic dystrophy (M) is rare disease and represents challenges to anesthesiologists. We report a case of adult patient with myotonic dystrophy who underwent laparoscopic cholecystectomy.     

Hemodynamic profile during laparoscopic cholecystectomy versus laparoscopic bariatric surgery: the impact of morbid obesity

The present study investigated the hemodynamic profile using impedance cardiography (ICG) monitor during pneumoperitoneum for laparoscopic cholecystectomy versus bariatric surgery in order to determine the impact of body weight on hemodynamics. METHODS. 32 adult patients (two groups, each 16 patients) were studied. Group 1 (16 patients) scheduled to undergo laparoscopic cholecystectomy (lapchole) with body mass index (BMI) 28 +/- 5 kg/m2. Group 2 (16 patients) scheduled to undergo laparoscopic adjustable band (LAGB) surgery for treatment of morbid obesity with BMI 45.3 +/- 8 kg/m2. under general anesthesia. Besides routine monitoring, impedance cardiography was used for hemodynamic monitoring. Three stages were identified for statistical analysis A, pre-insufflation, B, during vere pneumoperitoneum and C, at gas deflation. RESULTS. The mean values of cardiac index in group 1 at stages A, B and C were, 3.0 +/- 1.7, 2.5 +/- 0.5 and 2.7 +/- 0.5 L/min/m2 respectively with significant low values in stage B compared to stage A (p < 0.05). The same trend continue in group 2 where the mean values were, 2.4 +/- 0.6, 1.8 +/- 0.6 and 2.3 +/- 0.9 L/min/m2 respectively with significant differences compared to group 1 mean values (p < 0.05). Other hemodynamic variables showed non-significant differences (p > 0.05). CONCLUSIONS. Cardiac index showed significant decreasing trend in morbid obese patients compared to nonobese, which may reflect the effect of body weight on hemodynamics. On the other hand other hemodynamic parameters was not altered by body weight. We believe that hemodynamics should be closely monitored during laparoscopic surgery with pneumoperitoneum.     

Molecular analysis of Pasteurella multocida strains isolated from fowl cholera infection in backyard chickens

Objective

To characterize Pasteurella isolated from backyard chickens using whole cell protein lysate profiles and random amplified polymorphic DNA (RAPD) techniques to show their genetic relationship because Pasteurella multocida (P. multocida) is an important cause of fatal infections in backyard chickens.

Methods

Twenty one P. multocida isolates were recovered previously from clinical cases of fowl cholera belonging to individual owners and phenotypically analyzed using biochemical tests and serotyping were used for the genetic characterization.

Results

Phylogenetic study based on both methods revealed that the recovered population of P. multocida isolated from backyard chickens differs markedly, constituting a well-separated cluster and appearance of 3 distinguishing lineages with greater discrimination shown by RAPD-PCR that resulted in two suclusters in cluster A and three subclusters in cluster B and were related greatly with capsular serogroups for the examined strains. The whole cell protein revealed the presence of dominant protein bands at approximately 41 and 61 kDa in all of the examined isolates that may be a virulent proteins share in the increasing of its pathogenicity. Clear distinctive bands ranged from 123 to 1 554 bp.

Conclusions

Based on the previous findings, there are three spreading clusters that may indicate the association of a small number of P. multocida variants with the majority of cases suggesting that certain clones of P. multocida are able to colonize the examined backyard chickens. Also, the ease and rapidity of RAPD-PCR support the use of this technique as alternative to the more labour-intensive SDS-PAGE system for strain differentiation and epidemiological studies of avian P. multocida. Further application of RAPD technology to the examination of avian cholera outbreaks in commercially available flocks may facilitate more effective management of this disease by providing the potential to investigate correlations of P. multocida genotypes, to identify affiliations between bird types and bacterial genotypes, and to elucidate the role of specific bird species in disease transmission.