Ethnopharmacological survey of traditional drugs sold in the Kingdom of Jordan

The results of a survey of present-day traditional medicinal materials conducted in 1998-1999 in the Kingdom of Jordan are reported. The study covered selected markets of medicinal substances of ethnic communities throughout the kingdom, and also included questioning of the sellers about the healing characteristics of the various materials. The survey yielded information on many and varied medicinal substances, of which 304 are identified according to the following classifications: 236 species of plants (77.6%); 30 species of animals (9.8%); 29 kinds of inorganic substances (9.6%); and 9 materials of other or mixed origin (3%). Analysis of the data showed that some substances were of local origin (41.8%), but the majority of the substances (45.4%) were imported from other countries. 12.8% of the substances were both local and imported. These data demonstrate that there is still a flourishing and well-developed trade in these materials--a trade that is the remnant of a rich and ancient medical culture, which is disappearing from the modern world.     

Distribution of furamidine analogues in tumor cells: targeting of the nucleus or mitochondria depending on the amidine substitution

Diphenylfuran diamidines represent an important class of DNA minor groove binders of high therapeutic interest as antiparasitic or antitumor agents depending on the compounds structures. To exert their cytotoxic action, the compounds must first get into the cell and reach the nuclear compartment where the main target, DNA, is located. The forces that drive the drugs into cell nuclei, as well as the influence of the molecular structures on the cell distribution, are not known. To address these issues, we took advantage of the fluorescence of the molecules to analyze their intracellular distribution profiles in tumor cells of different origins (B16 melanoma, MCF7 mammary adenocarcinoma, A549 lung carcinoma, HT29 colon carcinoma, LNCaP, and PC3 prostatic carcinoma) by epifluorescence and confocal microscopy. A homogeneous series of synthetic bis-substituted alkyl or phenyl amidine and reverse amidine derivatives of furamidine was used to dissect the molecular mechanisms that control the distribution of the drugs into the cytoplasm or the nucleus of the cells. The amidine (DB75) and the various N-alkyl derivatives were found to accumulate selectively in the cell nuclei. This is also the case for a guanidine derivative but not for the phenyl-substituted compound DB569, which essentially localizes in cytoplasmic granules. Similar cytoplasmic patterns were observed with a reverse amidine analogue and a pyridine-substituted compound indicating that the presence of aromatic rings on the terminal side chain is the limiting factor that restricts the uptake of the compounds in the nuclear compartment. The use of different organelle-selective fluorescent probes, such as JC-1 and chloromethyl-X-rosamine, both specific to mitochondria and neutral red considered as a lysosome-selective probe, suggests that DB569 preferentially accumulates in mitochondria. Competition experiments with the antitumor drug daunomycin reveal that the diphenylfurans are attracted into the nuclei by the DNA. The DNA minor groove-drug interactions provide the driving force that permits massive accumulation of the fluorescent molecules in the nuclei. The DNA binding properties of the diphenylfuran derivatives were investigated by DNase I footprinting and surface plasmon resonance biosensor experiments to measure sequence selectivity and binding affinities, respectively. Furamidine and its phenyl-substituted analogue that accumulate in the cell nuclei and mitochondria, respectively, share a common selectivity for AT sites and bind equally tightly to these sites. Therefore, it is possible to modulate the intracellular distribution of the furamidine derivatives without affecting their DNA binding and sequence recognition properties. The introduction of aromatic substituents on diphenylfuran diamidines represents a novel strategy to control the intracellular compartmentalization of these DNA binding agents and directs them to mitochondria. This drug design strategy may prove useful to trigger drug-induced apoptosis.     

Immunohistochemical localization of three different prepro-GnRHs in the brain and pituitary of the European sea bass (Dicentrarchus labrax) using antibodies to the corresponding GnRH-associated peptides

The distribution of the cells expressing three prepro-gonadotrophin-releasing hormones (GnRH), corresponding to salmon GnRH (sGnRH), seabream GnRH (sbGnRH), and chicken GnRH-II (cGnRH-II) forms, was studied in the brain and pituitary of the sea bass (Dicentrarchus labrax) by using immunohistochemistry. To circumvent the cross-reactivity problems of antibodies raised to GnRH decapeptides, we used specific antibodies generated against the different sea bass GnRH-associated peptides (GAP): salmon GAP (sGAP), seabream GAP (sbGAP), and chicken-II GAP (cIIGAP). The salmon GAP immunostaining was mostly detected in terminal nerve neurons but also in ventral telencephalic and preoptic perikarya. Salmon GAP-immunoreactive (ir) fibers were observed mainly in the forebrain, although sGAP-ir projections were also evident in the optic tectum, mesencephalic tegmentum, and ventral rhombencephalon. The pituitary only receives a few sGAP-ir fibers. The seabream GAP-ir cells were mainly detected in the preoptic area. Nevertheless, sbGAP-ir neurons were also found in olfactory bulbs, ventral telencephalon, and ventrolateral hypothalamus. The sbGAP-ir fibers were only observed in the ventral forebrain, innervating strongly the pituitary gland. Finally, chicken-II GAP immunoreactivity was only detected in large synencephalic cells, which are the origin of a profuse innervation reaching the telencephalon, preoptic area, hypothalamus, thalamus, pretectum, posterior tuberculum, mesencephalic tectum and tegmentum, cerebellum, and rhombencephalon. However, no cIIGAP-ir fibers were detected in the hypophysis. These results corroborate the overlapping of sGAP- and sbGAP-expressing cells in the forebrain of the sea bass, and provide, for the first time, unambiguous information on the distribution of projections of the three different GnRH forms expressed in the brain of a single species.     

Bilateral medial rectus muscle recession: results in children with developmental delay compared with normally developed children.

PURPOSE: We sought to compare bimedial rectus muscle recession (BMR) results for esotropia in children with developmental delay with the results in normal children. METHODS: A retrospective analysis of all the children that underwent standard BMR surgery for esotropia during a 10 year period was undertaken. The surgical results of children with developmental delay were compared with those of normal children. RESULTS: In the developmentally delayed group, the mean angle of esotropia before surgery was 53+/-12 PD, the mean amount of medial rectus recession was 5.4+/-0.56 mm, 0.84 mm less than the standard amount of recession, and at the last follow-up visit only 56% achieved surgical success (within 10 PD of orthophoria). Among the failures, 86% were undercorrected, only one patient developed consecutive exotropia after surgery. In the developmentally intact group, the mean angle of esotropia before surgery was 37.4+/-8 PD, the mean amount of medial rectus recession was 5.2+/-0.65 mm, and 94% achieved surgical success. Among surgical failures, we observed only a single case of overcorrection. CONCLUSION: A higher rate of surgical failure was found in developmentally delayed children who received a smaller recession amount of the medial rectus muscles when compared with the developmentally normal children who received a standard amount of recession. The main reason for surgical failure in the developmentally delayed group, in a follow-up period of 2 years, was undercorrection of the angle of esotropia. It seems that decreasing the surgical table by a certain amount in children with developmental delay may lead to undercorrection. Therefore, we need to delineate the ideal amount of surgery in this unique group of individuals.     

The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study

Several studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.     

Pain relief in major trauma patients: an Israeli perspective

BACKGROUND: The pain of major trauma patients remains often unrelieved while in the emergency department. Our objective was to examine pain management in several trauma units, and to evaluate the impact of implementation of a trauma pain management protocol. METHODS: Current status was evaluated from questionnaires filled by trauma unit personnel of nine medical centers. In one, a pain management protocol was introduced. Staff and patients evaluated pain management before and after the protocol was instituted. RESULTS: About 80% of staff respondents from various centers were not aware of guidelines for pain management in trauma. The belief that pain assists diagnosis was the main reason (78.6%) for withholding analgesia. Large variability existed on what contraindicates analgesia, with the majority withholding analgesia in abdominal and multiple injuries. When administered, analgesia was delayed, and most commonly intramuscular meperidine was given. After the protocol's implementation, the personnel's awareness of analgesia increased, and consequently it was administered earlier and to more patients, mostly as intravenous morphine. Patients appreciated the timely analgesia (38% after vs. 14% before, p = 0.01), with fewer receiving none. Analgesia was considered beneficial by more patients (70% after vs. 23% before, p < 0.001), and enhanced cooperativity with personnel (p < 0.001). This was reflected in increased overall satisfaction with pain relief during the entire hospitalization. CONCLUSION: The importance of pain management protocols in major trauma was demonstrated by the response of personnel and patients.     

Splinting teeth--a review of methodology and clinical case reports

Splinting teeth to each other allows weakened teeth to be supported by neighbouring teeth, although the procedure can make oral hygiene procedures difficult. Several methods for splinting teeth, both extracoronal and intracoronal, as well as the materials commonly used for splinting, are described and illustrated. Two case reports are used to demonstrate the situations in which splinting might be appropriate.