Synthesis of new N-acryl-1-amino-2-phenylethanol and N-acyl-1-amino-3-aryloxypropanols and evaluation of their antihyperlipidemic, LDL-oxidation and antioxidant activity.

As a part of our drug discovery program, we identified an alkaloidal amide i.e. Aegeline (V) isolated from the leaves of Aegle marmelos as a dual acting agent (antihyperlipidemic and antihyperglycemic). In continuation of this program, we synthesized new N-acyl-1-amino-2-alcohols (N-acrylated-1-amino-2-phenylethanol and N-acylated-1-amino-3-aryloxypropanols) via Ritter reaction and screened for their in-vivo antihyperlipdemic activity in Triton induced hyperlipidemia model, LDL-oxidation and antioxidant activity. Compounds 3, 11 and 13 showed good antihyperlipidemic activity, LDL-oxidation as well as antioxidant activity and comparable activity with marketed antidyslipidemic drug.

Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol.

Ligands targeting central histamine H3 receptors (H3Rs) for epilepsy might be a promising therapeutic approach. Therefore, the previously described and structurally strongly related imidazole-based derivatives belonging to carbamate class with high H3R in vitro affinity, in-vivo antagonist potency, and H3R selectivity profile were investigated on their anticonvulsant activity in maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in Wistar rats. The effects of systemic injection of H3R ligands 1-13 on MES-induced and PTZ-kindled seizures were screened and evaluated against the reference antiepileptic drug (AED) Phenytoin (PHT) and the standard histamine H3R inverse agonist/antagonist Thioperamide (THP) to determine their potential as new antiepileptic drugs. Following administration of the H3R ligands 1-13 (5, 10 and 15 mg/kg, ip) there was a significant dose dependent reduction in MES-induced seizure duration. The protective action observed for the pentenyl carbamate derivative 4, the most protective H3R ligand among 1-13, was significantly higher (P <0.05) than that of standard H3R antagonist THP, and was reversed when rats were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10mg/kg), or with the CNS penetrant H1R antagonist Pyrilamine (PYR) (10mg/kg). In addition, subeffective dose of H3R ligand 4 (5mg/kg, ip) significantly potentiated the protective action in rats pretreated with PHT (5mg/kg, ip), a dose without appreciable protective effect when given alone. In contrast, pretreatment with H3R ligand 4 (10mg/kg ip) failed to modify PTZ-kindled convulsion, whereas the reference drug PHT was found to fully protect PTZ-induced seizure. These results indicate that some of the investigated imidazole-based H3R ligands 1-13 may be of future therapeutic value in epilepsy.

Antimicrobial efficacy in vivo of a new formulation of 2-butanone peroxide in n-propanol: comparison with commercial products in a cross-over trial.

The use of hand rub to obtain maximum decrease in bacterial load is important because the reduction needed to avoid transmission is unknown. The monomer of 2-butanone peroxide is a peroxygen derivative with potential biocidal use in hospitals. The aim of this study was to compare the efficacy of hand rub with an alcoholic solution of peroxide 2-butanone versus five antiseptic products, against E. coli K12 (CECT 433) transient flora acquired by hand immersion in a broth culture following the UNE-EN-1500 standard. Isopropanol 60% (control) obtained 99.99% reductions, driving down the bacterial load from 10(6) cfu/mL in the initial inocula to <100 cfu/mL. Products A, B and C (different alcoholic solutions ranging from 65% to 75% with low amounts of biguanidines and/or quaternary ammonium compounds) resulted in significantly lower amounts, reducing initial inocula to approximately 500 cfu/mL. Products D and E (70-75% alcohol solutions containing higher amounts of different quaternary ammonium compounds and triclosan in the case of product E) produced reductions similar to that of isopropanol, with significantly larger reductions than products A, B and C. The product with the solution of 2-butanone peroxide produced the same effect as products D and E with mean reductions of approximately 4log(10) (99.99%), driving the initial inocula down to < or = 100 cfu/mL, despite the low concentration (35%) of propanol in the solution. This novel peroxygen biocide offers high in-vivo cidal activity against acquired E. coli transient flora, offering an alternative to products with higher alcohol concentrations.

[Drug-induced pneumonitis in a patient treated with venlafaxine and propanolol]. / Pneumopathie médicamenteuse sous traitement par venlafaxine et propranolol.

INTRODUCTION: Venlafaxine and propranolol have rarely been identified as causes of pulmonary pathology. We describe a case of drug-induced pneumonitis occurring in a patient treated with these two medications. CASE REPORT: A 55 years old woman with liver cirrhosis treated with venlafaxine for 1 year and propranolol for 1 month was admitted to the intensive care unit because of acute respiratory failure. A Mycoplasma pneumoniae pneumonitis was diagnosed. After initial improvement under antibiotics, a new deterioration of respiratory status was observed 4 days after the reintroduction of venlafaxine and propranolol. Spontaneous recovery occurred after these treatments were withheld. Co administration of venlafaxine and propranolol, 2 drugs with affinity for the same cytochrome P450 isoenzyme (CYP2D6), may have contributed to drug accumulation and pulmonary toxicity. The liver cirrhosis of our patient may also have contributed to decreased cytochrome P450 enzymatic activity. CONCLUSIONS: Venlafaxine and propranolol share the same metabolic pathway and their co-administration may be complicated by drug induced pneumonitis.

An in-use microbiological comparison of two surgical hand disinfection techniques in cardiothoracic surgery: hand rubbing versus hand scrubbing.

Surgical site infection after heart surgery increases morbidity and mortality. The method of presurgical hand disinfection could influence the infection risk. From February to April 2003, we compared the microbiological efficacy of hand-rubbing (R) and hand-scrubbing (S) procedures. The surgical team alternately used hand-scrubbing or hand-rubbing techniques every two weeks. Fingertip impressions were taken before and immediately after hand disinfection, every 2h and at the end of the operation. Acceptability of hand rubbing was assessed by a questionnaire. Mean durations of surgical procedures were 259+/-68 and 244+/-69min for groups S and R respectively (P=0.43). Bacterial counts immediately after hand disinfection were comparable with the two techniques, but significantly lower in group R at the end of surgery. No differences were observed between the percentages of negative samples taken after 2h, 4h and at the end of surgery between the two groups. Bacterial skin flora reduction immediately after hand disinfection, after 2h and 4h of operating time and at the end of surgery was better in group R, but the difference was not statistically significant. Before surgery, the hand-rubbing method with alcohol solution preceded by hand washing with mild neutral soap is as effective as hand scrubbing to reduce bacterial counts on hands. It decreased the bacterial counts both immediately after hand disinfection and at the end of long cardiothoracic surgical procedures. The acceptability of hand rubbing was excellent and it can be considered to be a valid alternative to the conventional hand-scrubbing protocol.

Combined skin disinfection with chlorhexidine/propanol and aqueous povidone-iodine reduces bacterial colonisation of central venous catheters.

OBJECTIVE: Central venous catheter (CVC)-related infections may be caused by micro-organisms introduced from the skin surface into deeper tissue at the time of CVC insertion. The optimal disinfection regimen to avoid catheter-related infections has not yet been defined. This study compares three different approaches. DESIGN: Prospective randomised trial. SETTING: A tertiary care hospital. PATIENTS AND PARTICIPANTS: One hundred nineteen patients scheduled electively to receive 140 CVCs. INTERVENTIONS: Skin disinfection was performed with either povidone-iodine 10% (PVP-iodine), chlorhexidine 0.5%/propanol 70%, or chlorhexidine 0.5%/propanol 70% followed by PVP-iodine 10%. Prior to disinfection, a swab from the site of insertion was taken for culture. CVCs were removed if no longer needed or infection was suspected. All catheters were cultured quantitatively after removal. MEASUREMENT AND RESULTS: Bacteria could be isolated from 20.7% of the catheter tips. Bacterial growth was found in 30.8% of the catheters placed after skin disinfection with povidone-iodine, in 24.4% after disinfection with propanol/chlorhexidine and in 4.7% after disinfection with propanol/chlorhexidine followed by povidone-iodine ( p=0.006). In 15 cases, the same organism was isolated from the skin swab and the catheter tip. Ten of these paired isolates showed the same pattern in a pulsed-field gel electrophoresis analysis. CONCLUSIONS: Skin disinfection with propanol/chlorhexidine followed by PVP-iodine was superior in the prevention of microbial CVC colonisation compared to either of the regimens alone. These results support the concept that catheter infections can originate from bacterial translocation at the time of catheter insertion.

Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis

Fourty-five migraine without aura patients underwent a parallel double-blind trial aiming the comparison of the effects of propranolol 60 mg/day to flunarizine 10 mg/day and to propranolol 60 mg/day plus flunarizine 10 mg/day simultaneously. There were 3 groups, each one with 15 patients. After a 20-day-baseline period, each group received one kind of treatment during 120 days. Migraine index on propranolol was 23.4*, on flunarizine 18,7* and on both drugs 14.4*, mean frequency of attacks on propranolol was 1.26**, on flunarizine 1.2** and on both drugs, 1.13** (*p<0.05, **p<0.01 compared to baseline) and global evaluation was reduced with all forms of treatment. It was not found statistical differences between groups, nevertheless there was a trend in the group using two drugs reaching lower values in migraine index, frequency of attacks and global evaluation. In individuals using flunarizine (alone or associated with propranolol) the therapeutic effect was largely maintained up to 45 days after drug withdrawal.

Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis. A double-blind trial.

Fourty-five migraine without aura patients underwent a parallel double-blind trial aiming the comparison of the effects of propranolol 60 mg/day to flunarizine 10 mg/day and to propranolol 60 mg/day plus flunarizine 10 mg/day simultaneously. There were 3 groups, each one with 15 patients. After a 20-day-baseline period, each group received one kind of treatment during 120 days. Migraine index on propranolol was 23.4*, on flunarizine 18.7* and on both drugs 14.4*, mean frequency of attacks on propranolol was 1.26**, on flunarizine 1.2** and on both drugs 1.13** (*p < 0.05, **p < 0.01 compared to baseline) and global evaluation was reduced with all forms of treatment. It was not found statistical differences between groups, nevertheless there was a trend in the group using two drugs reaching lower values in migraine index, frequency of attacks and global evaluation. In individuals using flunarizine (alone or associated with propranolol) the therapeutic effect was largely maintained up to 45 days after drug withdrawal.

A comparison of two skin preps used in cardiac surgical procedures.

Postoperative surgical site infections contribute significantly to increased patient morbidity and mortality rates and unnecessary hospital costs. Effective and efficient preoperative patient skin preparation is an important perioperative nursing intervention that decreases the number of wound contaminants and reduces the risks for postoperative surgical site infections. This study examined the effectiveness and time and material costs of two preoperative patient skin prep methods (ie, isopropyl alcohol prep/iodophor-impregnated adhesive drape method, iodophor scrub and paint prep/plain adhesive drape method). The isopropyl alcohol prep/iodophor-impregnated adhesive drape method clinically was as effective as the iodophor scrub and paint prep/plain adhesive drape method, more cost-effective when time and materials were compared, and less cost-effective when materials alone were compared. To make appropriate decisions about the use of preoperative patient skin prep methods, perioperative nurse managers and staff members need to examine and determine whether costs in time or materials have the greater impact on their surgical settings.

Effects of isopropyl alcohol, ethanol, and polyethylene glycol/industrial methylated spirits in the treatment of acute phenol burns.

STUDY OBJECTIVE: To compare the effects of water rinse with those of isopropyl alcohol, polyethylene glycol with industrial methylated spirits, or ethanol on cutaneous phenol burns. DESIGN: Controlled trial with all animals receiving all treatments applied to different cutaneous phenol burn sites. TYPE OF PARTICIPANTS: Swine weighing 9 to 18 kg. INTERVENTIONS: In phase 1, each burn site was treated with water rinse for zero, one, or five minutes combined with either isopropyl alcohol, polyethylene glycol with industrial methylated spirits, ethanol, or no other treatment. Biopsies of treatment sites were done at 30 minutes and at 48 hours. In phase 2, a pilot study, the effect of isopropyl alcohol, polyethylene glycol with industrial methylated spirits, or water treatment on serum phenol levels was noted in animals with 5%, 10%, and 15% body surface area burns. MEASUREMENTS AND MAIN RESULTS: In phase 1, on histological examination of biopsy specimens, significant differences in tissue damage occurred among the groups (P < .05). Isopropyl alcohol and polyethylene glycol with industrial methylated spirits were the most efficacious treatments; the duration of water rinse had no significant effect. In phase 2, the systemic absorption of phenol may be greater with water treatment than with isopropyl alcohol treatment. CONCLUSION: Isopropyl alcohol and polyethylene glycol with industrial methylated spirits are equally effective in the amelioration of phenol burns of less than 5% total surface area. The wider availability of isopropyl alcohol makes it potentially the most useful treatment for these small burns. Further studies of its risks are needed.

Posttympanostomy otorrhea: the efficacy of canal preparation.

Otorrhea is the most common posttympanostomy complication. This study is designed to determine the efficacy of canal preparation prior to tympanostomy tube placement. One hundred thirty ears were prospectively randomized into prepared (Betadine and alcohol) and nonprepared (control) groups. Cultures obtained before, during, and after preparation were analyzed to determine the external canal flora and effectiveness of sterilization. Prepared ears and nonprepared control ears were examined for relation to otorrhea. Forty percent of the canals were sterile before preparation, and only 8% harbored suspected pathogenic organisms. Canal preparation successfully sterilized only 33% of the ears that contained bacteria. There was no difference in the otorrhea incidence among treatment groups (9.8%). Based on these bacteriologic and clinical findings, it is concluded that canal preparation with Betadine and alcohol does not reduce posttympanostomy otorrhea.

Handwashing and disinfection of heavily contaminated hands--effective or ineffective?

Hands are among the principal vehicles for transfer of nosocomial pathogens in hospitals. Often, outbreaks of infection are thought to be caused by a lack of compliance with handwashing guidelines, rather than due to the inadequacy of the handwashing agents used. In this study the effectiveness of proper handwashing and the use of three different hand disinfectants: ethanol 70% (E), isopropanol 40% (I) and alcoholic chlorhexidine (70%) (AC) was compared using three volunteers whose fingertips were heavily contaminated with a succession of bacteria including: Enterococcus faecalis, Staphylococcus aureus, Escherichia coli and Enterobacter cloacae. After each contamination, thorough handwashing and application of one disinfectant on the hands were performed three times. Fingerprint-samples were taken before and 1 min after application of the disinfectants. Thorough handwashing with an ordinary liquid soap ('Sterisol') did not reduce the confluent growth of bacteria on fingertips for any of the species used (197 examinations). Only AC had a significant effect on fingers heavily contaminated with S. aureus (126 examinations; AC compared with E and I; P less than 0.0002 and P less than 0.0002 respectively), but did not completely eradicate the bacteria. After contamination with Ent. cloacae (118 examinations), none of the three agents were particularly effective, but E and AC seemed to be somewhat more effective than I (P less than 0.0002 and P less than 0.01 respectively). When successive contamination was performed using all bacterial species, AC was the most effective decontaminant. However, Ent. cloacae was still present on the fingertips after 15 repeated courses of handwashing and applications of disinfectants. Bathing of hands in AC for 20s completely eradicated all bacteria from the hands. The study demonstrates that, when heavily contaminated, an ordinary handwashing followed by disinfectants is not enough to eradicate potentially pathogenic bacteria from the hands.

Fox-Fordyce disease: successful treatment with topical clindamycin in alcoholic propylene glycol solution.

We report a 66-year-old woman with a 3-year history of intensely pruritic follicular papules in the axillar, pubic and inguinal areas. Previous treatment with topical fusidic acid and gentamicin sulfate was ineffective. The clinical and histological examination was consistent with Fox-Fordyce disease. Application of clindamycin in an alcoholic propylene glycol solution led to the clearing of the lesions within 1 month. Nine months later, the treatment was stopped, and no recurrence was observed.

Propanolol reduces myocardial hypertrophy in the right cardiac chambers after infarction in rats

The effects of chronic propanolol (Prop) therapy on the post infarction myocardial hypertrophy of infarction rats were studied by histological techniques. male albino rats were submitted to left coronary artery ligation to produce infarction or to sham surgery (Con, N=6)., Infarction rats (Inf) were divided into 2 groups receiving Prop (2.5 mg/kg, twice a day, N+6) or saline (N=6) for one month, respectively. Myocyte diameters were measured in longitudinally oriented sections in the four heart chambers (60 cells/chamber). inf produced a significant increase in mean diameter of myocytes from the right atrium and ventricle and from the left atrium. In the right ventricle, myocyte diameter increased from 8.9 ñ 0.5 um in the Con group to 12.5 ñ 0.6 um in the the Inf group (P<0.05). Under Prop, myocyte diameter was reduced (P<0.05) to 9.8 ñ 0.9 um. Similar values were observed in the right atrium. In the left atrium, Prop produced only a partial reversion of the postinfarction hypertrophy. In the left ventricle, myocyte diameter was not significantly changed after Inf or Prop therapy. These data show that beta blockers reduce the myocardial hypertrophy in the right heart chambers after experimental infarcts in rats. This effect can be secondary to reduction of pulmonary hypertension or to blockade of direct effects of catecholamines on myocardial fibers or both