Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice

PURPOSE: Liposomal formulations of local anesthetics (LA) are able to control drug-delivery in biological systems, prolonging their anesthetic effect. This study aimed to prepare, characterize and evaluate in vivo drug-delivery systems, composed of large unilamellar liposomes (LUV), for bupivacaine (BVC) and mepivacaine (MVC). METHODS: BVC and MVC hydrochloride were encapsulated into LUV (0.4 micro m) composed of egg phosphatidylcholine, cholesterol and alpha-tocopherol (4:3:0.07 molar ratio) to final concentrations of 0.125, 0.25, 0.5% for BVC and 0.5, 1, 2% for MVC. Motor function and antinociceptive effects were evaluated by sciatic nerve blockade induced by liposomal and plain formulations in mice. RESULTS: Liposomal formulations modified neither the intensity nor the duration of motor blockade compared to plain solutions. Concerning sensory blockade, liposomal BVC (BVC(LUV)) showed no advantage relatively to the plain BVC injection while liposomal MVC (MVC(LUV)) improved both the intensity (1.4-1.6 times) and the duration of sensory blockade (1.3-1.7 times) in comparison to its plain solution (P < 0.001) suggesting an increased lipid solubility, availability and controlled-release of the drug at the site of injection. CONCLUSION: MVC(LUV) provided a LA effect comparable to that of BVC. We propose MVC(LUV) drug delivery as a potentially new therapeutic option for the treatment of acute pain since the formulation enhances the duration of sensory blockade at lower concentrations than those of plain MVC.     

Nutritional counseling with or without systematic use of oral nutritional supplements in head and neck cancer patients undergoing radiotherapy

Background

To evaluate the benefit of oral nutritional supplements (ONS) in addition to nutritional counseling in head and neck cancer (HNC) patients undergoing radiotherapy (RT).

Tracheal Mucus Velocity Remains Normal in Healthy Sheep Intubated with a New Endotracheal Tube with a Novel Laryngeal Seal

Background: Tracheal mucus velocity (TMV), an index of mucociliary clearance, is reduced markedly in patients intubated with standard endotracheal tubes (ETTs) with high-compliance low-pressure (hi-lo) cuffs. The authors developed a new ultra-thin walled ETT in which the inflatable cuff is replaced with a no-pressure seal, positioned at the level of the larynx. The seal consists of 12 to 20 toroidal layers of thin polyurethane film ("gills") at the level of the vocal cords and prevents both air leak and fluid aspiration. The authors hypothesized that ETTs with the new laryngeal seal may impair TMV less than ETTs with inflated hi-lo cuffs do.

Methods: The TMV was measured in seven healthy female sheep by radiographically tracking the motion of small discs of tantalum inserted into the trachea through a bronchoscope. The TMV was measured in spontaneously breathing sheep before intubation (baseline) and after intubation with either a hi-lo ETT (control group) or after intubation with a new ETT with gills (study group). Four to six weeks later, the studies were repeated, but the sheep that were previously in the control group served as the study group, and those in the study group served as controls.

Results: Baseline TMV did not differ in the two groups. In the control group, TMV decreased significantly (by 67%) from baseline. In the study group, TMV did not differ significantly from baseline and remained steady during 3 h of intubation.     

Antispasmodic activity of tiropramide

Tiropramide hydrochloride and some of its metabolites were studied in vivo for their antispasmodic activities on the following models: gastric emptying in the mouse retarded by cholecystokinin octapeptide (CCK-8) or morphine, progression of intestinal contents in the mouse, spontaneous motility of the colon in the anesthetized rabbit, diarrhea induced by castor oil in the rat, spasm of the sphincter of Oddi provoked by morphine in the guinea pig, contractions of the urinary bladder in the anesthetized rat. On these models tiropramide had an antispasmodic activity at doses of 4-40 mg/kg i.p. or i.v. and of 50-90 mg/kg orally. The potency was greater on "pathological" contractions or spasms and smaller on "physiological" movements. Tiropramide may therefore be regarded as a "eukinetic" antispasmodic agent. Tiropramide in general was more potent than reference agents such as papaverine or flavoxate and was active also after oral administration. The metabolites of tiropramide, i.e. CR 1034, CR 1098 and CR 1166 showed similar pharmacodynamic effects, but their potency was smaller than that of tiropramide. Large doses of tiropramide have depressive actions on the cardiovascular system, which can be seen especially if tiropramide is administered i.v. and are less pronounced after oral administration. The circulatory effects are therefore probably the limiting factor for increasing the parenteral doses of tiropramide in human therapy. Tiropramide was found less toxic than papaverine (LD50). The metabolites of tiropramide were less toxic than the parent compound. The toxicity of the chiralic forms of tiropramide does not differ significantly from that of the racemic substance.     

A multinational consensus on dysphagia in Parkinson's disease: screening,diagnosis and prognostic value

Journal of Neurology - Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though...     

The new Geriatric Nutritional Risk Index is a good predictor of muscle dysfunction in institutionalized older patients

BACKGROUND & AIMS: The validity of Geriatric Nutritional Risk Index (GNRI), in predicting nutrition-related risk of complications in the elderly, has been recently underscored. Malnutrition may results also in muscle function impairment. Thus, the present study aims to investigate if GNRI might be a reliable detector of muscle dysfunction in institutionalized older people. METHODS: In total, 153 institutionalized elderly (71 males, 82 females; mean age+/-SD: 75.2+/-8.4; range: 65-96) were studied in anthropometric parameters, serum albumin concentration and total score on GNRI. Muscle function was assessed by handgrip strength (HG). RESULTS: Women were significantly older than men and presented lower values of HG and arm muscle area (AMA). In overall population, GNRI was significantly correlated with AMA, HG and strength for centimeter of muscle area (HG/AMA); however, in gender-separated analysis, men presented higher degrees of correlation. After dividing patients in four categories according to GNRI, a more significant difference was detected in HG and HG/AMA rather than the other clinical and anthropometric parameters. Moreover, ANOVA analysis between HG quartiles was highly significant for GNRI, AMA and HG/AMA. CONCLUSIONS: GNRI is a good predictor of muscle dysfunction, particularly in men, and useful in identifying patients suitable for nutritional support and physical activity.     

Antibody to early antigens of varicella-zoster virus during varicella and zoster.

IgG antibody to the early antigens of varicella-zoster virus (VZV) was studied during both varicella and zoster by the indirect immunoperoxidase antibody technique. In parallel, complement-fixing, immune-adherence hemagglutinating, IgG, and IgM antibodies to VZV were studied. In both varicella and zoster infections, antibody to the early antigens of VZV appeared three to five days after onset of infection, reached a peak during the second week, and progressively decreased in titer until it disappeared, usually within two months. This antibody usually appeared slightly later than IgG or IgM antibody and grossly correlated with IgM antibody in varicella. In zoster infections, IgM antibody to VZV was not found by the immune-adherence hemagglutination assay at a titer of greater than or equal to 1:4, whereas antibody to the early antigens showed a curve similar to that found in varicella. It is suggested that antibody to the early antigens of VZV be considered as a marker of acute VZV infection, which is associated with a specific and significant IgM antibody response in varicella but not in zoster.