The concept of hybrid molecules of tacrine and benzyl quinolone carboxylic acid (BQCA) as multifunctional agents for Alzheimer's disease.

Novel tacrine-benzyl quinolone carboxylic acid (tacrine-BQCA) hybrids were designed based on multi-target directed ligands (MTLDs) paradigm, synthesized and evaluated in vitro as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). Tacrine moiety is represented herein as 7-methoxytacrine, 6-chlorotacrine or unsubstituted tacrine forming three different families of seven members, i.e. 21 compounds in overall. Introducing BQCA, a positive modulator of M1 muscarinic acetylcholine receptors (mAChRs), the action of novel compounds on M1 mAChRs was evaluated via Fluo-4 NW assay on the Chinese hamster ovarian (CHO-M1WT2) cell line. All the novel tacrine-BQCA hybrids were able to block the action of hAChE and hBChE in micromolar to nanomolar range. The hAChE kinetic profile of 5p was found to be mixed-type which is consistent with our docking experiments. Moreover, selected ligands were assessed for their potential hepatotoxicity on HepG2 cell line and presumable permeation through the blood-brain barrier by PAMPA assay. Expected agonistic profile towards M1 mAChRs delivered by BQCA moiety was not confirmed. From all the hybrids, 5o can be highlighted as non-selective cholinesterase inhibitor (hAChE IC50 = 74.5 nM; hBChE IC50 = 83.3 nM) with micromolar antagonistic activity towards M1 mAChR (IC50 = 4.23 µM). A non-selective pattern of cholinesterase inhibition is likely to be valuable during the onset as well as later stages of AD.

A 7-methoxytacrine-4-pyridinealdoxime hybrid as a novel prophylactic agent with reactivation properties in organophosphate intoxication.

Chemical warfare agents constitute an increasing threat to both military and civilian populations. Therefore, effective prophylactic approaches are urgently needed. Herein, we present a novel hybrid compound which is able not only to keep acetylcholinesterase resistant to organophosphate (OP) inhibitors, but also to serve as an enzyme reactivator in the case of OP intoxication.

QSAR analysis of salicylamide isosteres with the use of quantum chemical molecular descriptors.

Quantitative relationships between the molecular structure and the biological activity of 49 isosteric salicylamide derivatives as potential antituberculotics with a new mechanism of action against three Mycobacterial strains were investigated. The molecular structures were represented by quantum chemical B3LYP/6-31G( *) based molecular descriptors. A resulting set of 220 molecular descriptors, including especially electronic properties, was statistically analyzed using multiple linear regression, resulting in acceptable and robust QSAR models. The best QSAR model was found for Mycobacterium tuberculosis (r(2)=0.92; q(2)=0.89), and somewhat less good QSAR models were found for Mycobacterium avium (r(2)=0.84; q(2)=0.78) and Mycobacterium kansasii (r(2)=0.80; q(2)=0.56). All QSAR models were cross-validated using the leave-10-out procedure.

QSAR study of antimycobacterial activity of quaternary ammonium salts of piperidinylethyl esters of alkoxysubstituted phenylcarbamic acids.

A series of 17 halogenides of quaternary ammonium salts of the alkylpiperidinylethyl esters of 2-pentoxy (and 2-heptoxy) substituted phenylcarbamic acids were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, and M. avium. Correlation of this action with lipophilicity (log P, 1-octanol-water system) was used for the description of the structure-antimycobacterial activity relationships (QSARs). The activity increased with the increasing lipophilicity of the compounds.

1-Aryl-5-benzylsulfanyltetrazoles, a new group of antimycobacterial compounds against potentially pathogenic strains.

A set of 21 1-phenyl-5-benzylsulfanyltetrazoles substituted on the phenyl ring as well as on the benzyl moiety was evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of M. kansasii. We tried to use the Hansch approach, the Free-Wilson approach and their combination for structure-activity correlation but the calculations were statistically insignificant.

Chronic wounds and delusions of parasitosis in the drug abuser.

Plastic surgeons are routinely consulted about the care of difficult or chronic wounds. Most of these wounds have a physiologic basis and are treated according to basic wound-healing principles. Patients with factitious wounds are difficult to treat and present diagnostic dilemmas. We present a case and review of the literature of drug-induced delusions of parasitosis to inform plastic surgeons of this important entity and for consideration in the differential diagnosis of chronic wounds.

The role of tissue expansion in the reconstruction of secondary burn defects.

Tissue expansion has become firmly established as an acceptable and useful modality in the treatment of various soft tissue defects. This article relates our experience with this technique for the reconstruction of secondary burn deformities in 26 patients. Details of expander placement and use are discussed, as well as the results and complications in this series. The advantages of this method, including a superior quality reconstruction, limited donor site morbidity, and cost-effectiveness, are discussed. The disadvantages of several operative steps, multiple office visits, and the objectionable appearance during expansion are enumerated. Guidelines for patient selection and technique refinements are also considered to reduce complications and to achieve an optimal functional and aesthetic result.

Merkel tumor of the lower lip: a case report and updated review of the literature work performed at the University of Illinois.

An unusual case of Merkel cell carcinoma of the lower lip with metastasis to the submental nodes is presented. Clinical similarities and the histopathologic and prognostic differences between this tumor and basal or squamous cell carcinomas of the head and neck area are discussed and the current thoughts for treatment are presented. The capricious clinical course and the aggressive nature of the Merkel cell tumor is emphasized. A review of the existing literature is also included in an effort to familiarize the head and neck surgeon with this relatively new but potentially lethal pathological cutaneous entity.

Further applications of Archimedes' principle in the correction of asymmetrical breasts.

Archimedes' law of buoyancy has been extended to the preoperative bedside assessment of volume differences between breasts, whatever their cause. The simple method described has proved to be a helpful aid in surgical procedures for the correction of breast asymmetry.

The use of Clinitron therapy unit in the immediate postoperative care of pressure ulcers.

The conventional postoperative care of patients undergoing pressure ulcer operations is complicated and unsatisfactory. In an effort to improve this care, we used the Clinitron therapy unit, which provides a true flotation environment for the patient. The surface pressure on the skin constantly remains below the capillary closure pressure of 32 mm Hg, and therefore no change in the patient's position is required as with the other beds currently used. Its special design creates a bactericidal fluid medium in which the temperature can be controlled. Our experience with 16 patients using the Clinitron in the immediate postoperative period has been encouraging. Comments from the patients and the nursing and medical staff, as well as advantages and disadvantages of this modality are discussed.

Early treatment of rhinophyma--a neglected entity?

Patients are aware when even minimal bulbosity appears secondary to acne rosacea. Many suffer psychic trauma as a result. Early surgical treatment of this entity eliminates disfiguring hypertrophy. We advocate early surgical treatment of even minimal rhinophyma.

Mucociliary flow in the canine frontal sinus.

The mucociliary flow in the frontal sinus of dogs is in a spiral pattern from medial to lateral. The final evacuation of mucus is through the ostium positioned anteriorly. Mucus flow rate is most rapid in the areas of the ostium and slowest in the area of the intersinus septum. Mucus flow patterns remain the same despite removing the intersinus septum and blocking one frontal sinus ostium. Mucociliary flow rate, however, appears to be diminished in the reoperated frontal sinus. Mucus does not appear to migrate readily across the intersinus septal areas when the septum has been removed and one nasofrontal duct is obstructed.

Treatment of the patient with extensive osteoradionecrosis of the mandible.

The management of osteoradionecrosis of the mandible remains controversial. Involvement of large areas of the mandible or the entire mandible with osteoradionecrosis may result in severe functional disability and cosmetic deformity. Pain, trismus, difficulty with speech and eating, and a malodorous wound are all problems that must be corrected. Local forms of therapy may be inadequate in the treatment of extensive osteoradionecrosis, and more aggressive surgical management is required. The extent of surgical intervention depends on the individual case. However, preservation of function and avoidance of disfigurement are important goals in the treatment plan. From both a functional and cosmetic standpoint, surgical management can be effective in achieving satisfactory rehabilitation goals.