High blood pressure. Causes, symptoms, treatments

Synthesis of "neoprofen", a rigidified analogue of ibuprofen, exemplifying synthetic methodology for altering the 3-D topology of pharmaceutical substances.


NeoProfen (sterile preservative-free ibuprofin L-lysine at 17 mg/mL in a single-use glass vial) is used to close a clinically significant patent ductus arteriosus in premature infants no more than 32 weeks gestational age. The neonatal population is especially sensitive to outside chemical, physical and environmental conditions because of incompletely developed organ systems, low birth weight and other underlying conditions. Two batches of this product were voluntarily recalled by the manufacturer, Lundbeck, and investigated for the source of particulate matter observed during a commercial stability testing program. This was found to result from an interaction between the product and the Type I borosilicate glass vial where ibuprofen substitutes for the aluminum oxide network in the glass, forming an ibuprofen aluminum hydroxide salt as particulate. In order to prevent this salt formation an alternate glass vial was chosen which had interiors treated using a chemical vapor deposition technique. These vials were found to preserve NeoProfen quality properties during short term stress and medium term stability studies.

The unfolding pathway of the defatted human serum albumin (HSA) binding ibuprofen and propofol has been studied by using small-angle X-ray scattering (SAXS) and the support of circular dichroism data. A set of HSA solutions with urea concentrations between 0.00 and 9.00 M was analyzed, and the singular value decomposition method applied to the complete SAXS data set allowed us to distinguish four different states in solution. Besides the native and unfolded forms, two intermediates I1 and I2 have been identified, and the low-resolution structures of these states were obtained by exploiting both ab initio and rigid body fitting methods. The I1 structure was characterized by only one open domain (domain I, which does not host a binding site for either of the ligands), whereas I2 presents only one closed domain (domain III). A direct comparison with the unfolding pathway of the HSA:Ibu complex (Galantini et al. Biophys. Chem. 2010, 147, 111-122) pointed out that the presence of propofol as a second ligand, located in subdomain IIIB, leads to the appearance of an intermediate with two closed domains (domains II and III), which are those that accommodate the ligands. Moreover, the equilibrium between I2 and the unfolded form is slightly shifted toward higher urea concentrations. These results suggest that the cobinding significantly hinders the unfolding process.

The clinical trial protocol was approved by the responsible German state Ethics Board, and the Federal Institute for Drugs and Medical Devices. The study complies with the Declaration of Helsinki, the principles of Good Clinical Practice and all further applicable regulations. This safety and pharmacokinetics trial informs the planning of a subsequent randomised controlled trial. Regardless of the result of the primary and secondary outcome assessments, the clinical trial will be reported as a publication in a peer-reviewed journal.

We performed a systematic review according to the guidelines of the Cochrane Collaboration. Randomised trials reporting conservative treatments in patients with TTH with headache as outcome were included. In the analysis studies were grouped according to type of intervention: acute pain medication, preventive medication, physiotherapy interventions, behavioural interventions and interventions in children.

Of the total number of cases, abnormal HSG findings were seen in 55 patients. Majority of the patients were between 26-30 years age group with 6-10 years duration of subfertility. The tubes were occluded in 34.28% of cases in the ratio of 1:8, proximal occlusion being the commonest. 5.71% showed hydrosalpinx. Beaded & wiry appearances of tubes were seen in 2.85% of cases. Amongst the uterine anomalies, which accounted for 20% of cases, only five patients had acquired abnormality. In the congenital group maximum number of patients had hypoplastic uterus (52.38%) followed by bicornuate uterus. Unicornuate and arcuate uterus accounted for 9.52% each. Intravasation of contrast occurred in two patients.

The aim of this study was to investigate whether local anesthesia of abdominal wall wounds prior to laparoscopic cholecystectomy leads to decreased pain beyond the immediate postoperative period and thus improves the comfort of the patient. In a randomized, double-blind study 50 patients scheduled for laparoscopic cholecystectomy were divided into two groups. In one group (n = 25) the skin, subcutis, fascia, muscle, and preperitoneal space were infiltrated with 8 ml of bupivacaine 0.5% 5 min before each abdominal wall incision. The control group (n = 25) received normal saline. The intensity of pain was assessed by a 100-point visual analogue scale (VAS) at rest and during movement and by the consumption of analgesics. Analgesic therapy was provided by on-demand analgesia with piritramide intravenously for 24 h and continued by ibuprofen orally on request. The mean intensity of pain at rest and during movement was lower but not statistically significant in patients who received bupivacaine compared to the control group up to the second postoperative day. The difference was between 4 and 9 VAS points and therefore of doubtful clinical relevance. Similar statistically nonsignificant results were found for the mean consumption of piritramide up to 16 h after the operation. Three patients (12%) in the bupivacaine group localized the most severe pain up to the second postoperative day to the right lower abdominal wall wound where the gallbladder had been extracted compared to 11 patients (44%) of the control group (P = 0.012). These results indicate that bupivacaine was effective at the site where it was administered.(ABSTRACT TRUNCATED AT 250 WORDS)