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1.
Scientifica (Cairo) ; 2014: 180353, 2014.
Article in English | MEDLINE | ID: mdl-25140277

ABSTRACT

Whereas nutrition has a crucial role on sport performance, it is not clear to what extent nutrition knowledge is associated with physical fitness. The aim of this study was to examine the current level of nutrition knowledge of soccer players and whether this level is associated with physical fitness. Soccer players (n = 185, aged 21.3 ± 4.9 yr, weight 72.3 ± 8.4 kg, and height 177.5 ± 6.4 cm) performed a battery of physical fitness tests (sit-and-reach test, SAR; physical working capacity in heart rate 170, PWC170; and Wingate anaerobic test, WAnT) and completed an 11-item nutrition knowledge questionnaire (NKQ). Low to moderate Pearson correlations (0.15 < r < 0.34, p < 0.05) of NKQ with age, weight, height, fat free mass (FFM), SAR, peak power, and mean power of WAnT were observed. Soccer players with high score in NKQ were older (4.4 yr (2.2; 6.6), mean difference (95% confidence intervals)) and heavier (4.5 kg (0.6; 8.3)) with higher FFM (4.0 kg (1.1; 6.8)) and peak power (59 W (2; 116)) than their counterparts with low score. The moderate score in the NKQ suggests that soccer players should be targeted for nutrition education. Although the association between NKQ and physical fitness was low to moderate, there were indications that better nutrition knowledge might result in higher physical fitness and, consequently, soccer performance.

2.
Reprod Toxicol ; 46: 98-105, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24685944

ABSTRACT

The aim of this study was to evaluate fetal exposure to organophosphate pesticides (OPs) by measuring their non-specific dialkyl-phosphate metabolites (DAPs) in amniotic fluid (AF), and to examine the potential association between prenatal exposure and fetal growth. AF samples were collected from 415 women during the second gestational trimester. The determined OPs metabolites were DMP, DMTP, DEP, DETP, and DEDTP. DAPs were extracted by liquid-solid extraction, derivatized and analyzed by gas chromatography-mass spectrometry. 97.8% of AF samples were positive for at least one DAP. DAPs levels did not differ between urban and rural areas. Macrosomic neonates have significantly higher sum levels of DMPs (p=0.043), which exerted a linear positive association with birth-weight centile (b=4.43, p=0.016). Conclusively, as DAPs are detectable in AF they may be used as a potential biomarker of fetal exposure to OPs. Sum levels of DMPs appear to be associated with birth weight independently of other covariates.


Subject(s)
Amniotic Fluid/chemistry , Biomarkers/analysis , Organophosphates/metabolism , Organophosphates/toxicity , Adult , Environmental Exposure , Female , Greece , Humans , Infant, Newborn , Maternal Age , Pesticides , Pregnancy , Reproducibility of Results
3.
Transplant Proc ; 43(5): 1537-43, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21693231

ABSTRACT

BACKGROUND: The use of kidneys from elderly deceased donors has substantially increased organ supply, although it is associated with worse graft function and survival rates. The risk of kidneys from elderly donors as well as expanded criteria donors (ECDs) on kidney transplant outcome was investigated. PATIENTS AND METHODS: Seventy-five kidney transplants from ECDs over a 5-year period were reviewed retrospectively. Old age and increased donor risk variables were analyzed separately in relation to graft function and survival. RESULTS: Sixty-four of 75 (85.3%) recipients had functioning grafts 5 years posttransplant. The overall actuarial graft survivals from 1 to 5 years were 87.5%, 68.1%, 57.3%, 55.4%, and 47.3%, respectively. Early graft function gave 47 (62.7%) kidneys remarkable actuarial survivals of 100.0%, 88.3%, 75.8%, 75.8%, and 68.4% at 1 to 5 years posttransplant, and 28 (37.3%) kidneys had delayed graft function with substantially decreased actuarial survival rates, ranging from 66.7% to 23.2%. Kidneys from elderly donors had considerable actuarial graft survival rates of 100.0%, 83.3%, 76.9%, 76.9%, and 67.0% from 1 to 5 years, respectively; these were the best graft survival rates compared with kidneys from the other donor categories. The other donor risk variables when associated with advanced age of any had an adverse effect on recipient graft function and survival, but no single risk variable alone, or a combination of any two, showed any statistically significant variability. CONCLUSION: Elderly kidney donors provided a substantial organ pool expansion without affecting patient and graft survival in many patients. ECDs can be utilized safely if adequate measures are taken.


Subject(s)
Age Factors , Graft Survival , Kidney Transplantation , Tissue Donors , Aged , Humans , Kidney Function Tests , Retrospective Studies
4.
Chirurgia (Bucur) ; 103(3): 351-3, 2008.
Article in English | MEDLINE | ID: mdl-18717287

ABSTRACT

The abdominal intraperitoneal cerebrospinal fluid pseudocyst is a rare but important complication in patients with ventriculoperitoneal shunts. We report a case of a 31-year-old female, in which a large abdominal pseudocyst was developed 1 year after insertion of a ventriculoperitoneal shunt for hydrocephalus. The abdominal CT scan and the ultrasonographical evaluation of the abdomen showed a well defined, cystic mass lesion with a volume of 50 cm3, in the recessus hepato-renal. The peritoneal tip of the shunt was located within the mass lesion. A distal externalization of the peritoneal catheter without excision of the pseudocyst was performed. Cerebrospinal fluid culture demonstrated a Staphylococcus epidermis infection and adequate antibiotic treatment was administrated. The previous symptoms improved 4 weeks later and a new catheter was placed intraperitoneally in a different quadrant. The postoperative course was uneventful. We suggest that chronic inflammation or subclinical peritonitis is a predisposing factor for this complication.


Subject(s)
Cysts/microbiology , Staphylococcal Infections/complications , Staphylococcus epidermidis/isolation & purification , Ventriculoperitoneal Shunt/adverse effects , Adult , Anti-Bacterial Agents/therapeutic use , Cysts/diagnosis , Cysts/drug therapy , Diagnosis, Differential , Female , Humans , Hydrocephalus/surgery , Peritoneal Cavity/surgery , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Treatment Outcome
5.
Transplant Proc ; 40(5): 1386-90, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18589113

ABSTRACT

Urological complications after renal transplantation increase morbidity, delay graft function, and occasionally lead to graft and/or patient loss. The aim of this study was to analyze the causes of and therapeutic approaches to urological complications in renal transplantation as they related to patient outcomes. A series of 1525 consecutive renal transplantations were performed over a 24-year period. Renal grafts were obtained in 814 cases from living-related and in 711 from cadaveric donors. A Lich-Gregoire ureterovesical reimplantation technique with minimal bladder wall dissection was employed in all cases. Ureteral stents were routinely used in cadaveric transplants and exceptionally among living-related grafts. Urological complications were classified according to the mechanism and site of urinary tract involvement: graft ureteropelvic junction obstruction/stenosis (A), ureteral obstruction/stenosis (B), ureterovesical anastomosis obstruction/stenosis (C), urinary leakage (D), and other (E). Overall, we encountered 96 urological complications (6.3%). Group C complications occurred in 29 cases (30.2%), followed by 27 cases (28.1%) for group B patients, 25 cases (26.0%) for group D, 12 cases (12.5%) for group A, and 3 cases (3.1%) for group E patients. Surgical intervention was required in 49 (51.0%) of all urological complications. The others (n = 47, 49.0%) were treated either conservatively or by minimally invasive procedures. A rapid diagnosis of urological complications, assisted by early posttransplant DTPA scans, routine ultrasonography, and especially prompt treatment, resulted in compensation of renal graft dysfunction in the vast majority (n = 90, 93.8%) of cases. Surgical techniques of graft retrieval and reimplantation are of utmost importance to minimize the incidence of urological complications.


Subject(s)
Kidney Transplantation/adverse effects , Urologic Diseases/epidemiology , Female , Greece , Humans , Living Donors , Male , Retrospective Studies , Stents , Ureteral Obstruction/epidemiology , Ureteral Obstruction/surgery , Urologic Diseases/surgery
6.
Transplant Proc ; 40(5): 1391-6, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18589114

ABSTRACT

PURPOSE: To evaluate the efficacy of percutaneous angioplasty and stenting in cases of artery stenosis of the transplanted kidney or proximal iliac artery stenosis causing transplant dysfunction and/or increase of the arterial blood pressure. MATERIALS AND METHODS: Between January 1999 and June 2007, we evaluated 24 patients who had undergone renal transplantation and subsequently were diagnosed with refractory hypertension and transplant dysfunction for signs of possible renal transplant artery stenosis. Color Doppler ultrasonography and magnetic resonance angiography preceded the intrarterial angiographic investigation, with false-negative results in 18.2% and 13.6% of patients, respectively. In 2 of the 24 patients, angiography did not reveal arterial stenosis affecting the transplanted kidney. Two patients had severe ipsilateral iliac artery stenosis and the remaining 20 had transplant artery stenosis. Successful angioplasty and stenting were performed in these 22 patients. RESULTS: The method was technically feasible in 100%. The procedure-related morbidity was 0%. During the follow-up period (range: 3 to 104 months), two patients died with normal transplant function, two suffered transplant failure, and the remaining 18 still have normal transplant function and easily controlled hypertension. CONCLUSION: Percutaneous angioplasty and stenting in cases of arterial stenosis affecting the renal transplant function are safe and effective procedures. Even more, the strong clinical suspicion must lead to angiographic investigation regardless of the results of other imaging approaches.


Subject(s)
Angioplasty , Kidney Transplantation/adverse effects , Renal Artery Obstruction/epidemiology , Renal Artery Obstruction/surgery , Stents , Angioplasty, Balloon, Coronary , Cadaver , Creatinine/blood , Humans , Hypertension/etiology , Living Donors , Reoperation/statistics & numerical data , Retrospective Studies , Tissue Donors , Treatment Outcome
7.
Transplant Proc ; 38(9): 3147-50, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17112923

ABSTRACT

Diabetic muscle infarction (DMI) is a rare, long-term complication of poorly controlled diabetes (typically of type I). DMI was first described in 1965 and more than 100 cases have been reported thereafter in the English literature. Usually, there is a coexistence with concomitant nephropathy, neuropathy, and retinopathy. The etiology remains uncertain, but appears to be attributable to diabetic microangiopathy and hypercoagulability and is believed that hypoxia-reperfusion injury is involved. DMI presents with sudden onset of pain associated with a tender mass in the thigh in most instances. The diagnosis is based on magnetic resonance imaging, which is not specific but highly indicative. Treatment is conservative with relapses occurring in 50% of the patients, but not necessarily in the same muscle group. We describe a case of DMI that occurred 4 months after simultaneous kidney and pancreas transplantation in one patient with type I diabetes mellitus and end-stage renal disease.


Subject(s)
Diabetes Mellitus, Type 1/surgery , Diabetic Nephropathies/surgery , Infarction/diagnosis , Kidney Transplantation , Muscle, Skeletal/blood supply , Pancreas Transplantation , Adult , Anti-Bacterial Agents/therapeutic use , Drug Therapy, Combination , Female , Humans , Kidney Function Tests , Magnetic Resonance Imaging , Muscle, Skeletal/pathology , Postoperative Complications , Treatment Outcome
8.
Ultrastruct Pathol ; 28(4): 181-97, 2004.
Article in English | MEDLINE | ID: mdl-15693630

ABSTRACT

Electron microscopy defined classic patterns of hereditary glomerular disease long before genetics revealed an underlying specific mutation. Genetic analysis is now easier to perform in clinical practice but an earlier optimism that genetics would predict disease severity and phenotype is challenged. The classic paradigm is Alport nephritis in which only a subset of mutations may predict glomerular abnormalities and disease severity. Interpretation of ultrastructural pathology of monogenetic diseases like Alport nephritis is complicated when the proband is the first family member to be diagnosed or there is discrepancy between clinical presentation and ultrastructural changes. In this review the authors have selected a dozen cases representative of common monogenetic glomerular diseases as a platform to discuss the utility of diagnostic electron microscopy in the era of molecular genetics. The emphasis is on genotype/glomerular phenotype correlations.


Subject(s)
Kidney Diseases/genetics , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Kidney Glomerulus/ultrastructure , Microscopy, Electron, Transmission , Adolescent , Adult , Aged , Child, Preschool , Female , Genotype , Humans , Infant , Kidney Glomerulus/physiology , Male , Phenotype
9.
Article in English | MEDLINE | ID: mdl-12241028

ABSTRACT

The prevalence of parasitic infections responsible for the condemnation of carcasses and viscera during meat inspection, and their economic implication, was estimated in a year long abattoir survey of 10 277 slaughtered farm animals in the region of Trikala, Greece. The organs examined for the presence of parasitic lesions during meat inspection were: liver and lungs of all animals, rumen of cattle, small intestine of lambs and kids, and muscles of cattle and swine. The parasitic lesions observed in the lungs of cattle, sheep and goats were caused only by hydatid cysts. No hydatid cysts were observed in the lungs of swine. The parasitic lesions observed in the liver of cattle, sheep and goats were as a result of hydatid cysts and flukes of Fasciola hepatica and Dicrocoelium dendriticum, while those of swine were due to milk spots only. Moniezia sp. proglottids were found in the small intestine of lambs only. The prevalence of parasites responsible for the condemnation of marketable organs was low (0.26%). Parasites were responsible for 22% of the total of condemned organs, and their annual cost was 99, 00 GDR (approximately 292 Euros). The parasites most contributing to marketable organ condemnation were hydatid cysts (26%) and D. dendriticum flukes (26%).


Subject(s)
Animal Diseases/epidemiology , Dicrocoeliasis/veterinary , Echinococcosis/veterinary , Abattoirs/statistics & numerical data , Animal Diseases/economics , Animal Diseases/parasitology , Animals , Cattle , Cattle Diseases/epidemiology , Cattle Diseases/parasitology , Dicrocoeliasis/epidemiology , Dicrocoelium/isolation & purification , Echinococcosis/epidemiology , Food Inspection , Goat Diseases/epidemiology , Goat Diseases/parasitology , Goats , Greece/epidemiology , Liver/parasitology , Lung/parasitology , Meat/economics , Prevalence , Seasons , Sheep , Sheep Diseases/epidemiology , Sheep Diseases/parasitology , Swine , Swine Diseases/epidemiology , Swine Diseases/parasitology
10.
Vet Parasitol ; 97(4): 285-93, 2001 Jun 28.
Article in English | MEDLINE | ID: mdl-11390082

ABSTRACT

Information concerning worm control practices of pig farmers in Greece was collected through a questionnaire survey by visiting farms and interviewing farmers. Questionnaires from 93 farmers were collected. The most commonly treated age groups of pigs were sows (87%), followed by fatteners (59%) and weaners (57%). Most of the farmers treated their sows twice per year (78%). The preferred method for calculating anthelmintic dosages was visual estimation (77%) of an average body weight (97%). Drug administration was by mixing anthelmintics with 1-day ration (97%) in two doses with an interval of 4-5 days (94%). The most commonly used group of anthelmintic was benzimidazoles and probenzimidazoles (37-46%), followed by avermectins (7-14%) and tetrahydropyrimidines (8-14%). Febantel was the most commonly used individual drug (34-40%), followed by ivermectin (7-14%) and pyrantel (9-14%). A small number of pig farmers used more than one group of anthelmintics (1-4%) or individual drug (2-6%) in the same year. The majority of the farmers (60%) used the same anthelmintic group for 3 or more years. When gilts/sows or boars were brought, 55% of the pig farmers did not treat with an anthelmintic. Most of the farmers evaluated the efficacy of an anthelmintic by inspecting the general appearance of the pigs or by inspecting for the presence of worms expelled in the faeces after treatment. Planning of the anthelmintic treatment strategy for most of the farms was the responsibility of veterinarians. However, most of the farmers considered the magnitude of worm infection in their own farm as insignificant.


Subject(s)
Animal Husbandry/methods , Anthelmintics/administration & dosage , Strongylida Infections/veterinary , Strongylida/growth & development , Swine Diseases/prevention & control , Adult , Animals , Female , Greece , Humans , Male , Middle Aged , Strongylida/drug effects , Strongylida Infections/parasitology , Strongylida Infections/prevention & control , Surveys and Questionnaires , Swine , Swine Diseases/parasitology
11.
Biochim Biophys Acta ; 1509(1-2): 346-60, 2000 Dec 20.
Article in English | MEDLINE | ID: mdl-11118545

ABSTRACT

Losartan was found to affect both the thermotropic behavior and molecular mobility of dimyristoyl- and dipalmitoyl-phosphatidylcholine membranes (Theodoropoulou and Marsh, Biochim. Biophys. Acta 1461 (1999) 135-146). At low concentrations, the antagonist is located close to the interfacial region of the phosphatidylcholine bilayer while at high mole fractions it inserts deeper in the bilayers. In the present study, we investigated the interactions of losartan with phosphatidylethanolamine membranes using differential scanning calorimetry (DSC), electron spin resonance (ESR) and 31P nuclear magnetic resonance (NMR) spectroscopy. DSC showed that the antagonist affected the thermotropic transitions of dimyristoyl-, dipalmitoyl- and dielaidoyl-phosphatidylethanolamine membranes (DMPE, DPPE and DEPE, respectively). ESR spectroscopy showed that the interaction of losartan with phosphatidylethanolamine membranes is more superficial than in the case of phosphatidylcholine bilayers. Additionally, losartan increased the spin-spin broadening of 12-PESL spin labels in the gel phase of DMPE and DPPE membranes, while in the case of DEPE membranes the opposite effect was observed. (31)P-NMR showed that the antagonist stabilizes the fluid lamellar phase of DEPE membranes relative to the hexagonal H(II) phase. Our results show that losartan affects the thermotropic behavior of phosphatidylethanolamine membranes, while the molecular mobility of the membranes is not affected greatly. Furthermore, its interactions with phosphatidylethanolamine membranes are more superficial than with phosphatidylcholine bilayers.


Subject(s)
Angiotensin Receptor Antagonists , Lipid Bilayers/chemistry , Losartan/pharmacology , Calorimetry, Differential Scanning , Electron Spin Resonance Spectroscopy , Magnetic Resonance Spectroscopy , Phosphatidylethanolamines/chemistry , Temperature
12.
Biochim Biophys Acta ; 1461(1): 135-46, 1999 Nov 09.
Article in English | MEDLINE | ID: mdl-10556495

ABSTRACT

We used differential scanning calorimetry (DSC) and electron spin resonance (ESR) spectroscopy to investigate the interactions of Losartan, a potent, orally active Angiotensin II AT(1) receptor antagonist with phospholipid membranes. DSC results showed that Losartan sensitively affected the chain-melting behavior of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) bilayer membranes. ESR spectroscopy showed that phosphatidylcholines spin-labeled at the 5-position of the sn-2 acyl chain (n-PCSL with n=5), incorporated either in DMPC or DPPC bilayers containing Losartan, were restricted in motion both in the gel and in the liquid-crystalline membrane phases, indicating a location of the antagonist close to the interfacial region of the phosphatidylcholine bilayer. At high drug concentrations (mole fraction >/= x=0.60), the decrease in chain mobility registered by 5-PCSL in fluid-phase membranes is smaller than that found at lower concentrations, whereas that registered by 14-PCSL is further increased. This indicates a different mode of interaction with Losartan at high concentrations, possibly arising from a location deeper within the bilayer. Additionally, Losartan reduced the spin-spin broadening of 12-PCSL spin labels in the gel-phase of DMPC and DPPC bilayers. As a conclusion, our study has shown that Losartan interacts with phospholipid membranes by affecting both their thermotropic behavior and molecular mobility.


Subject(s)
Angiotensin Receptor Antagonists , Losartan/chemistry , Membrane Lipids/chemistry , Calorimetry, Differential Scanning , Electron Spin Resonance Spectroscopy , Lipid Bilayers/chemistry , Molecular Structure , Phospholipids/chemistry , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Spin Labels
13.
J Pharm Biomed Anal ; 18(6): 947-56, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9925329

ABSTRACT

The synthetic cannabinoid (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]+ ++pyranyl)-2-hexyl-1,3-dithiolane (AMG-3) is a cannabimimetic molecular probe with one of the highest binding affinities reported to date. Therefore, due to its potential pharmacological importance, its structure was sought to be elucidated and its conformational properties were studied using a combination of 1D, 2D NMR spectroscopy and molecular modelling. The structure of its methylated analog (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H dibenzo [b,d]pyranyl-1-methoxy)-2-hexyl-1,3 dithiolane (AMG-18), was also studied and its conformational properties were compared with AMG-3. AMG-18 lacks of the phenolic hydroxyl group a strict requirement for cannabimimetic activity and is almost devoid of any biological activity. The conformational analysis studies showed that 1',1' dithiolane ring restricted the orientation preferences of alkyl chain. This may account for the high binding affinity of AMG-3 to cananbinoid receptors. Grid scan search studies showed different preferences of possible adopting dihedral values of phenolic hydroxyl group and its methyl ether. These observations may account for their differences in biological activity.


Subject(s)
Cannabinoids/chemistry , Magnetic Resonance Spectroscopy , Methylation , Models, Molecular , Molecular Conformation
14.
Life Sci ; 62(20): 1901-10, 1998.
Article in English | MEDLINE | ID: mdl-9600331

ABSTRACT

Differential Scanning Calorimetry (DSC) has been applied to study the thermal properties of the membrane perturbing antibacterial octyl- and dodecyl-bromide salts of quaternary dimethylamino adamantanol (ADM-8 and ADM-12 correspondingly) incorporated in free or complexed form with beta-cyclodextrin (beta-CD) into dipalmitoylphosphatidylcholine (DPPC) containing bilayers. The DSC results showed that the studied compounds exert pronounced thermotropic changes in DPPC bilayers when inserted as free molecules. These effects are reduced when are present in a complex form with beta-CD. Since the studied compounds exert destructive effects in membrane bilayers their insertion in membrane bilayers as complexes with cyclodextrin may result in differentiation of their activity. The obtained results suggest that their complexation with beta-CD may improve their biological profile. It also increases their aqueous solubility, a limited factor for their use as drugs.


Subject(s)
1,2-Dipalmitoylphosphatidylcholine/chemistry , Adamantane/analogs & derivatives , Alcohols/chemistry , Cyclodextrins/chemistry , Hot Temperature , Lipid Bilayers/chemistry , Membranes, Artificial , beta-Cyclodextrins , Adamantane/chemistry , Calorimetry, Differential Scanning/methods , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Solubility
15.
J Pharm Biomed Anal ; 16(5): 741-51, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9535185

ABSTRACT

Linomide is a new synthetic immunomodulator which exerts prominent anti-autoimmune effects in various experimental models. Recently, it was tested in clinical trials to patients suffering from multiple sclerosis and showed to inhibit the activity of the disease. Therefore, due to its pharmacological importance, we attempted elucidate its structure using one-dimensional and two-dimensional nuclear magnetic resonance (NMR) techniques and study its conformational properties using a combination of two-dimensional NMR spectroscopy and molecular modeling. The conformational analysis of linomide was based on the measurement of interproton nuclear Overhauser enhancement (NOE) values obtained from a two-dimensional NMR spectrum and a number of molecular modeling techniques used to calculate the low energy conformers of this compound. This information will serve as an aid to synthetic chemists whom their research activity is focused on developing linomide analogs with better biological profiles.


Subject(s)
Adjuvants, Immunologic/chemistry , Hydroxyquinolines/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure
16.
J Pharm Biomed Anal ; 16(5): 723-32, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9535183

ABSTRACT

The structure of 11-benzoyl-9,9a,10,11-tetrahydro-4H-indolo [4,3-ab] carbazole, a candidate molecule to possess significant antitumor or antimicrobial activity, was elucidated using a combination of one-dimensional and two-dimensional nuclear magnetic resonance (NMR) techniques. Its conformational properties were studied using a combination of two-dimensional NOESY spectroscopy and molecular modeling. Such information will be of aid to synthetic chemists who aim to develop derivatives of this structure. It may also provide information about the stereoelectronic requirements that govern their activities.


Subject(s)
Anti-Infective Agents/chemistry , Antineoplastic Agents/chemistry , Carbazoles/chemistry , Indoles/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation
17.
Biochim Biophys Acta ; 1328(1): 65-73, 1997 Aug 14.
Article in English | MEDLINE | ID: mdl-9298946

ABSTRACT

We have used a combination of high-resolution solid-state 13C-NMR and DSC (differential scanning calorimetry) to study the distinctively different thermotropic and dynamic properties of the anaesthetic steroid alphaxalone and its inactive congener delta16-alphaxalone in dipalmitoylphosphatidylcholine (DPPC) model membranes. In the solid-state 13C-NMR, the techniques included cross polarization (CP) and/or magic angle spinning (MAS). The observed data revealed the following important results. (a) DSC as a bulk method showed that the active steroid lowers the main phase transition temperature and broadens the pretransition more significantly than the inactive congener. The 13C-CP/MAS experiments allowed us to detect the pretransition temperature in the alphaxalone-containing preparation, which was not discernible in DSC. (b) The chemical shift values varied with temperature, indicating different degrees of trans-gauche isomerization in the lipid acyl chains when the bilayer is in the liquid crystalline phase. (c) Only specific additional peaks appeared in the 13C-CP/MAS spectra when each of the steroids was present in the preparation. delta16-alphaxalone gives rise to more additional peaks than alphaxalone, indicating a different mobility of the corresponding molecular moiety in the phospholipid bilayer environment. (d) The relative intensities of these peaks also confirmed that alphaxalone is fully incorporated in the bilayer, whereas delta16-alphaxalone is only partially so. These results suggest that the differential effects of these two analogues in the membrane may, at least in part, explain the reason for their different biological activities.


Subject(s)
Anesthetics/analysis , Lipid Bilayers/chemistry , Magnetic Resonance Spectroscopy/methods , Pregnanediones/analysis , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Calorimetry, Differential Scanning , Membrane Fluidity , Temperature
18.
J Int Med Res ; 25(3): 135-40, 1997.
Article in English | MEDLINE | ID: mdl-9178145

ABSTRACT

This experimental study in rats was designed to investigate the tolerability and the mode of healing when commercial relon mesh is used in the repair of large abdominal-wall defects. A defect was created to simulate anatomical derangement of the abdominal wall and a surgical correction was performed using relon mesh. The mesh was implanted intraperitoneally in 18 Wistar albino rats. The animals were killed under anaesthesia 4, 6, 8, 12, 15 or 30 days later and the intra-abdominal viscera were examined macroscopically for adhesions and other evidence of inflammatory reactions. Skin healing usually occurred within 7-8 days of surgery. Microscopic studies were used to confirm the gross findings and showed that maturation of granulation tissue, fibrocyte invasion with encapsulation of the mesh and the appearance of newly formed vessels occurred 2 weeks after surgery. Within 4 weeks a strong layer of connective tissue was present. The relon mesh was tolerated well. These results indicate that the use of relon mesh may provide a cheap alternative means of repairing large abdominal-wall defects.


Subject(s)
Abdominal Muscles/surgery , Skin Transplantation/methods , Surgical Mesh , Wound Healing/physiology , Abdominal Muscles/abnormalities , Abdominal Muscles/pathology , Animals , Male , Rats , Rats, Wistar , Skin Transplantation/pathology , Time Factors
19.
Chem Phys Lipids ; 84(1): 21-34, 1996 Nov 01.
Article in English | MEDLINE | ID: mdl-8952050

ABSTRACT

Thio analogs of platelet activating factor (PAF) are of great interest because they exhibit antineoplastic properties both in vitro and in vivo. In contrast to most known anticancer agents, these lipids appear not to act through the synthesis and function of DNA and, therefore, offer a new avenue of approaching cancer chemotherapy. We have examined the conformational properties of 1-thiohexadecyl-2-O-methyl-S-glycero-3-phosphocholine (ET-S-16-OCH3) in organic solvents and in micelles. The conformational analysis was based on a combination of 1D, 2D NMR spectroscopy and molecular graphics. 1H and 13C spin lattice relaxation time (T1) experiments were also performed to study the dynamic properties of this molecule. The picture emerging from these studies is as follows. The alkyl chain of ET-S-16-OCH3 is the most mobile part of the molecule both in CDCl3/CD3OD and in micelles and exists as a mixture of interconverting conformers including an extended all trans and several low energy conformers with one or more gauche segments. This creates a twisting of the chain and facilitates a spatial communication between the alkyl chain and the glycerol backbone as well as between the alkyl chain and the headgroup. The methylene groups of the thioglycerol backbone and the headgroup are the least mobile while the methine group of the thioglycerol backbone appears to have an intermediate mobility. The conformation of the thioether lipid in the two media may be of relevance during its interaction with its site of action, the cellular membrane. Such a conformation may also play an important role in determining the selectivity of this interaction with different cell membranes.


Subject(s)
Antineoplastic Agents/chemistry , Phospholipid Ethers/chemistry , Phospholipid Ethers/pharmacology , Phosphorylcholine/analogs & derivatives , Antineoplastic Agents/pharmacology , Glycerol/analogs & derivatives , Magnetic Resonance Spectroscopy , Micelles , Models, Molecular , Molecular Conformation , Molecular Structure , Phospholipid Ethers/chemical synthesis , Platelet Activating Factor/analogs & derivatives
20.
Biochim Biophys Acta ; 1281(2): 235-44, 1996 Jun 11.
Article in English | MEDLINE | ID: mdl-8664323

ABSTRACT

We have studied the thermotropic properties of a wide variety of cannabinoids in DPPC bilayers. The molecules under study were divided into four classes: (a) classical cannabinoids possessing a phenolic hydroxyl group; (b) delta9-THC metabolites with an additional hydroxyl group on the C ring; (c) non-classical cannabinoids, and (d) cannabinoids with a protected phenolic hydroxyl group. The results showed that the first three groups have similar effects on the thermotropic properties of DPPC bilayers up to x = 0.05 (molar ratio) and that these effects do not parallel their biological activity. For concentrations less than x = 0.01, cannabinoids affect mainly the pretransition temperature in a progressive manner until its final abolishment. At x = 0.05, they further affect the main phase transition by lowering its phase transition temperature and broadening its half width. At high concentrations the thermograms have multiple components, indicating that membranes are no longer homogeneous but rather consist of different domains. At these concentrations cannabinoids with more hydroxyl groups give simpler thermograms. Low concentrations of cannabinoids in group d affect significantly the pretransition temperature, while high concentrations affect only marginally the main phase transition by slightly lowering its temperature and broadening its half width. These results point out the importance of the phenolic hydroxyl group in inducing membrane perturbations. The d-spacing data from our small angle X-ray diffraction experiments show that delta8-THC produces significant structural changes in the lipid bilayer, including the gel-phase tilting angle, the intermolecular cooperativity and the gauche:trans conformer ratio. Conversely, the inactive analog Me-delta8-THC does not cause drastic changes to the bilayer structure.


Subject(s)
1,2-Dipalmitoylphosphatidylcholine/chemistry , Calorimetry, Differential Scanning , Cannabinoids/pharmacology , Lipid Bilayers/chemistry , X-Ray Diffraction , Cannabinoids/chemistry , Molecular Structure , Thermodynamics
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