Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"

Structural variants of the hydrophobic side chain ("C region") of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (45Ca2+ influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, < 55) in order to obtain high potency. Combination of the information gained here about the "C-region" of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.     

Selection of window sizes for optimizing occupational comfort and hygiene based on computational fluid dynamics and neural networks

The present paper presents a novel computational method to optimize window sizes for thermal comfort and indoor air quality in naturally ventilated buildings. The methodology is demonstrated by means of a prototype case, which corresponds to a single-sided naturally ventilated apartment. Initially, the airflow in and around the building is simulated using a Computational Fluid Dynamics model. Local prevailing weather conditions are imposed in the CFD model as inlet boundary conditions. The produced airflow patterns are utilized to predict thermal comfort indices, i.e. the PMV and its modifications for non-air-conditioned buildings, as well as indoor air quality indices, such as ventilation effectiveness based on carbon dioxide and volatile organic compounds removal. Mean values of these indices (output/objective variables) within the occupied zone are calculated for different window sizes (input/design variables), to generate a database of input–output data pairs. The database is then used to train and validate Radial Basis Function Artificial Neural Network input–output “meta-models”. The produced meta-models are used to formulate an optimization problem, which takes into account special constraints recommended by design guidelines. It is concluded that the proposed methodology determines appropriate windows architectural designs for pleasant and healthy indoor environments.     

Conformational transition of insulin induced by n-alkyltrimethylammonium bromides in aqueous solution

A surfactant-induced conformational transition of bovine insulin has been detected by difference spectroscopy for a homologous series of n-alkytrimethylammonium bromides, chain length C10-C16 at pH 10.0, 25 degrees C. The transition was followed as a function of surfactant concentration by absorbance measurements at 275 nm and the data were analysed to obtain the Gibbs energy of the transition in water (delta Gw degree) and in a hydrophobic environment (delta Ghc degree) for saturated protein-surfactant complexes. A value of delta Gw degree of -11.8 +/- 1.8 kJ mol-1 was found independent of n-alkyl chain length, which is similar to the value found for the n-alkylsulfate-induced transition in a previous study (-14.6 +/- 3.0 kJ mol-1). The values of delta Ghc degree were in the range approximately -88 to -100 kJ mol-1 for chain lengths from C10 to C16. The values of delta Ghc degree vs. chain length for both the n-alkyltrimethylammonium bromides and the n-alkylsulfates lie on the same curve, demonstrating that delta Ghc degree is independent of the nature of the surfactant head group.     

Use of a subcutaneous glucose sensor to detect decreases in glucose concentration prior to observation in blood

The development of a hypoglycemic alarm system using a subcutaneous glucose sensor implies that a decrease in blood glucose is rapidly followed by a decrease in the signal generated by the sensor. In a first set of experiments the linearity and the kinetics of the response of sensors implanted in the subcutaneous tissue of normal rats were investigated during a progressive increase in plasma glucose concentration: the sensitivities determined between 5 and 10 mM and between 10 and 15 mM were not significantly different, and a 5-10 min delay in the sensor's response was observed. In a second set of experiments, performed in diabetic rats, the kinetics of the decrease in subcutaneous glucose concentration following insulin administration was monitored during a decrease in plasma glucose level, from 15 to 3 mmol/L. During the 20 first min following insulin administration, the sensor monitored glucose concentration in subcutaneous tissue with no lag time. Subsequently, the decrease in the estimation of subcutaneous glucose concentration preceded that of plasma glucose. This phenomenon was not observed when the same sensors were investigated in vitro during a similar decrease in glucose concentration and may be due to a mechanism occurring in vivo, such as the effect of insulin on glucose transfer from the interstitial space to the cells surrounding the sensor. It reinforces the interest of the use of implantable glucose sensors as a part of a hypoglycemic alarm.     

Non-penetrating deep sclerectomy (NPDS) with or without collagen device (CD) in primary open-angle glaucoma: middle-term retrospective study

The purpose of this study is to evaluate the middle-term tonometric results of a new filtering procedure, the nonpenetrating deep sclerectomy with or without collagen device, in primary open-angle glaucoma. This technic aims to eliminate or minimize the complications of classical trabeculectomy. METHOD: This procedure was carried out by Koslov and colleagues. This is performed under a limbal-based conjunctival flap and a superfical scleral flap, the ablation of a deep scleral flap taking away the external wall of Schlemm's canal, only living in place the Descemet membrane. One must obtain a visible filtration across the opened Schlemm's canal and Descemet membrane. To improve the aqueous filtration, a cylindric collagen device, made from porcine scleral tissue, biocompatible, known for its high water content, is fixed in the deep scleral bed with a 10/0 nylon suture. This device provides a support for the elimination route of aqueous humor and acts like a sponge, carrying the liquid by capillary action. It is sterilized by irradiation. Full guarantee against viral contamination is provided. This procedure ends in one suture (10/0 nylon) of superficial scleral flap and conjunctival closing suture. When NPDS is performed without CD a sponge of 5FU is used and the superficial scleral flap is not sutured. RETROSPECTIVE STUDY: Our material included 111 patients, 148 eyes in CD group; 43 patients, 55 eyes in the group without CD. The average follow-up was 13.3 +/- 5.8 months in the CD group, 7.2 +/- 3.5 months in the group without CD. All patients presented a POAG without risk factors of bleb failure. RESULTS: The delta average IOP before the operation and at the end of the follow-up period was 7.2 +/- 6.3 mmHg in the CD group; 8.3 +/- 7.6 mmHg in the group without CD (no significant difference). The probability-success rate with the Kaplan-Meier method (IOP < or = 20 mmHg) was, in the CD group, at 18 months, 68% and 69% in the group without CD, without medical treatment. With monotherapy, the success rate was 85% in the CD group, 74% in the group without CD (p < or = 0.05). PROSPECTIVE STUDY: Afterwards, we have conducted a prospective study comparing two groups of patients with POAG without risk factors of bleb failure, operated with and without collagen device, without 5FU in the second group. Our material included 31 patients, 31 eyes, one eye for each patient, two surgeons; 17 eyes in the CD group, 14 eyes in the group without CD. The average age was 65.8 +/- 8.2 years in the first group; 64.1 +/- 10.3 in the second group. The average follow-up was 11 months in both groups. RESULTS: delta average IOP was 8.3 +/- 5.8 in the CD group; 12.3 +/- 6 in the group without CD (p < 0.05). The probability-success rate without treatment at 12 months: 58% in the first group, 90% in the second group (p < 0.05) and with monotherapy: 80% and 90% (N.S.). In both studies, in both groups, except microperforations, more frequent in the prospective group without CD, no complications of the trabeculectomy were observed. The mean change in visual acuity was inferior to 0.1 at the end of the follow-up. A postoperative rise in IOP can occur. It can be due to an internal obstruction (goniosynechiae or bad filtration). It can be treated with Nd-Yag laser. It can also be due to external obstruction, treated by 5FU injections into the bleb. The success of these procedures were similar in the whole group. CONCLUSION: Non penetrating deep sclerectomy can be considered as an excellent alternative to trabeculectomy in open and wide angles. It does not modify visual acuity. It carries away less complications than trabeculectomy and the use of antimitotic agents is safer. Collagen device does not seem, at middle-term, to improve tonometric results.