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1.
Pediatr Surg Int ; 40(1): 245, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39192007

ABSTRACT

PURPOSE: A multidisciplinary approach to Inflammatory Bowel Disease (IBD) has recently demonstrated a positive impact in pediatric patients, reducing dropout rates and facilitating the transition to adult care. Our study aims to evaluate how this approach influences disease activity, dropout rates, and transition. METHODS: We conducted a longitudinal observational study including all patients diagnosed with IBD during pediatric-adolescent age, with a minimum follow-up period of 12 months. For each patient, endpoints included therapeutic approach, need for surgery and transition features. RESULTS: We included 19 patients: 13 with Ulcerative Colitis (UC) and 6 with Crohn's disease (CD). Most patients required multiple lines of therapy, with over 50% in both groups receiving biological drugs. Compliance was good, with a single dropout in each group (10, 5%). The need for surgery was significantly higher in the CD group compared to the UC group (16% vs. 7.7%, p < 0.01). Mean age at transition was significantly higher in the UC group compared to the CD group (19.2 ± 0.7 years SD vs. 18.3 ± 0.6 years SD, p < 0.05). CONCLUSIONS: In our experience, the multidisciplinary approach to IBD in transition-age patients appears effective in achieving clinical remission, offering the potential to reduce therapeutic dropouts.


Subject(s)
Inflammatory Bowel Diseases , Transition to Adult Care , Humans , Female , Male , Adolescent , Longitudinal Studies , Inflammatory Bowel Diseases/therapy , Child , Crohn Disease/therapy , Young Adult , Colitis, Ulcerative/therapy , Patient Care Team , Follow-Up Studies
2.
ESMO Open ; 9(8): 103666, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39137479

ABSTRACT

BACKGROUND: In patients with cancer, lean body mass loss is frequent and associated with worse outcomes, including reduced treatment tolerance and survival. Bioelectrical impedance analysis (BIA) is a popular method for body composition assessment. We evaluated the value of BIA-derived body composition parameters in predicting mortality and, for the first time, dose-limiting toxicity (DLT). PATIENTS AND METHODS: We conducted a prospective multicenter (n = 12) observational study in adult patients with solid neoplastic disease and receiving primary systemic treatment. We collected information on BIA-derived parameters: phase angle (PhA) <5th percentile of age and gender-specific normative values; standardized PhA (SPA) <-1.65; Nutrigram® <660 mg/24 h/m and <510 mg/24 h/m for males and females, respectively. The primary outcome and the key secondary were 1-year mortality and DLT (any-type severe toxicity requiring a delay in systemic treatment administration or a reduction of its dosage), respectively. RESULTS: In total, 640 patients were included. At 12 months, death occurred in 286 patients (47.6%). All BIA-derived body composition parameters were independently associated with death: SPA, hazard ratio (HR) = 1.59 [95% confidence interval (CI) 1.30-1.95] (P < 0.001); PhA, HR = 1.38 (95% CI 1.13-1.69) (P = 0.002); Nutrigram®, HR = 1.71 (95% CI 1.42-2.04) (P < 0.001). DLT occurred in 208 patients (32.5%) and body composition parameters were associated with this outcome, particularly SPA: odds ratio = 6.37 (95% CI 2.33-17.44) (P < 0.001). CONCLUSIONS: The study confirmed that BIA-derived body composition parameters are independently associated not only with survival but also with DLT. Although our findings were limited to patients receiving first-line systemic treatment, the evidence reported may have important practice implications for the improvement of the clinical work-up of cancer patients.


Subject(s)
Body Composition , Electric Impedance , Neoplasms , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Neoplasms/mortality , Neoplasms/drug therapy , Prospective Studies
3.
Nutr Metab Cardiovasc Dis ; 23(3): 264-71, 2013 Mar.
Article in English | MEDLINE | ID: mdl-21906920

ABSTRACT

BACKGROUND & AIMS: To investigate the association between anthropometric indices of body fat distribution and cardiometabolic risk factors in a population of Parkinson's disease (PD) patients. METHODS & RESULTS: One hundred and fifty-seven PD patients (57.3% males) were studied measuring: waist circumference (WC), waist-hip ratio (WHR), waist-to-height ratio (WtHR), body fat percentage (BF%) by impedance, fasting glucose, serum lipids. Information was collected also on diabetes, hypertension and metabolic syndrome (MetS). Increased cardiometabolic risk was defined by ≥2 MetS component traits other than abdominal adiposity. In the whole population, prevalence of overweight and obesity were 35.0% and 19.2%, respectively. However, prevalence of MetS and elevated cardiometabolic risk were 14.6% and 18.5%, respectively. Prevalence was similar between genders, with one exception: adverse fat distribution according to WC and WHR was more common in females (P < 0.001). Using a multivariable model (adjustments: age, smoking status and disease duration), indices were highly correlated with BF% in both genders. WC and WtHR were associated with the number of MetS criteria and elevated risk. The only cardiometabolic parameters associated with anthropometric indices were HDL in men and triglycerides in women. After adjusting also for BMI all the associations found with anthropometric indices disappeared. CONCLUSIONS: Despite their correlation with BF%, anthropometric indices of body fat distribution appear to poorly account for the reduced cardiometabolic risk of the PD patient. This finding suggests a low metabolic activity within the adipose tissue. The implications of fat distribution on the cardiometabolic risk of PD patients clearly deserves further investigation.


Subject(s)
Body Fat Distribution/adverse effects , Hypertension/epidemiology , Metabolic Syndrome/epidemiology , Obesity/epidemiology , Parkinson Disease/epidemiology , Adipose Tissue/metabolism , Adiposity , Aged , Anthropometry , Blood Glucose/analysis , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Humans , Hypertension/etiology , Male , Metabolic Syndrome/complications , Middle Aged , Nutrition Assessment , Obesity/complications , Parkinson Disease/complications , Prevalence , Risk Factors , Triglycerides/blood
5.
J Nutr Health Aging ; 21(6): 655-661, 2017.
Article in English | MEDLINE | ID: mdl-28537329

ABSTRACT

OBJECTIVES: The aim of this systematic review was to summarize the evidence on the efficacy of high-calorie, high-protein nutritional formula enriched with arginine, zinc, and antioxidants (disease-specific support) in patients with pressure ulcers (PUs). METHODS: Randomized controlled trials in English published from January 1997 until October 2015 were searched for in electronic databases (EMBASE, Medline, PubMed, and CINAHL). Studies comparing a disease-specific nutritional support (oral supplements or tube feeding) to a control nutritional intervention enabling the satisfaction of energy requirements regardless of the use of high-calorie formula or placebo or no support for at least 4 weeks were considered eligible. Study outcomes were the percentage of change in PU area, complete healing and reduction in the PU area ≥40% at 8 weeks, and the percentage of change in area at 4 weeks. RESULTS: A total of 3 studies could be included in the meta-analysis. Compared with control interventions, formulas enriched with arginine, zinc and antioxidants resulted in significantly higher reduction in ulcer area (-15.7% [95%CI, -29.9, -1.5]; P=0.030; I2=58.6%) and a higher proportion of participants having a 40% or greater reduction in PU size (OR=1.72 [95%CI, 1.04, 2.84]; P=0.033; I2=0.0%) at 8 weeks. A nearly significant difference in complete healing at 8 weeks (OR=1.72 [95%CI, 0.86, 3.45]; P=0.127; I2=0.0%) and the percentage of change in the area at 4 weeks (-7.1% [95%CI, -17.4, 3.3]; P=0.180; I2=0.0%) was also observed. CONCLUSIONS: This systematic review shows that the use of formulas enriched with arginine, zinc and antioxidants as oral supplements and tube feeds for at least 8 weeks are associated with improved PU healing compared with standard formulas.


Subject(s)
Antioxidants/therapeutic use , Arginine/therapeutic use , Dietary Supplements , Enteral Nutrition , Pressure Ulcer/therapy , Wound Healing/drug effects , Zinc/therapeutic use , Energy Intake , Humans , Nutritional Support , Outcome Assessment, Health Care
6.
J Ethnopharmacol ; 96(3): 371-4, 2005 Jan 15.
Article in English | MEDLINE | ID: mdl-15619554

ABSTRACT

Passiflora alata (Passifloraceae) is a native plant from the South-America tropical forest that provides a much appreciated fruit known as "maracujá-doce". Although tea of the leaves of Passiflora alata is used in folk medicine as a sedative and tranquilizer, there are no investigations about its effects on biochemical parameters in blood or from its major chemical composition. The purpose of this study was to evaluate the effects of the tea of the leaves of Passiflora alata on biochemical parameters (antioxidant system, glucose and cholesterol levels) and to perform a phytochemical investigation of the tea. We isolated and identified two saponins and five C-glycosylflavones derived from apigenin, luteolin and chrysoeriol. Three of them are new in this species. Passiflora alata extract was administrated orally in rats at dose of 1000 mg/kg and it was observed an increase in high-density lipoprotein level (HDL-cholesterol).


Subject(s)
Passiflora , Animals , Apigenin/chemistry , Apigenin/isolation & purification , Blood Glucose/drug effects , Blood Proteins/metabolism , Body Weight/drug effects , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Flavones/chemistry , Flavones/isolation & purification , Flavonoids/chemistry , Flavonoids/isolation & purification , Glutathione Peroxidase/blood , Luteolin/chemistry , Luteolin/isolation & purification , Male , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Rats , Rats, Wistar , Saponins/chemistry , Saponins/isolation & purification , Superoxide Dismutase/blood , Triglycerides/blood
7.
J Nutr Health Aging ; 19(9): 947-54, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26482698

ABSTRACT

OBJECTIVES: To collect information on actual nutritional intervention requirements in long-term care institutions and on the role of institutional factors in nutritional care. DESIGN: A cross-sectional analysis of baseline data (collected between September 2011 and September 2013) within the context of a multicenter prospective cohort study. SETTING: Nineteen long-term care institutions. PARTICIPANTS: Thirteen hundred and ninety-four resident elderly (age ≥60 years). MEASUREMENTS: The prevalence of nutritional derangements (MNA-Short Form) and the need to introduce nutritional interventions on the residents. RESULTS: Prevalence of malnutrition and risk of malnutrition were 35.2% [95%CI, 32.8-37.8] and 52.6% [95%CI, 50.0-55.2], respectively. Malnutrition was more frequent upon admission and in larger institutions (≥50 beds). Overall, 50% of the residents requiring an individualized nutritional care plan (any type) were not receiving it. Oral diet, the use of fluid thickeners and oral nutritional supplements had to be introduced in 306 (22.5%), 201 (15%) and 175 (13%) residents, respectively. The need to implement the oral diet was mainly due to inadequacy of texture according to chewing and swallowing capabilities. In gender and age-adjusted multivariable logistic regression models, nutritional interventions were associated with worse nutritional status (P<0.001 for all). Moreover, while the duration of stay was unrelated to the need for nutritional interventions, we observed that residents living in larger long-term care institutions (≥50 beds) were more likely to require improvement in nutrition care. CONCLUSIONS: In long-term care elderly residents nutritional derangements are very common, underdiagnosed and undertreated. Nutritional screening should be part of routine care. However, also the systematic involvement of a nutritional care specialist appears to be an urgent need, particularly in larger institutions where the standards of care are likely to be lower.


Subject(s)
Diet , Health Services Needs and Demand , Long-Term Care , Malnutrition/diet therapy , Nursing Homes , Nutritional Requirements , Nutritional Status , Aged , Aged, 80 and over , Cohort Studies , Cross-Sectional Studies , Dietary Supplements , Eating , Feeding Behavior , Female , Geriatric Assessment , Humans , Male , Malnutrition/epidemiology , Malnutrition/prevention & control , Nutrition Assessment , Nutritional Support , Patient Care Planning , Prevalence , Prospective Studies
8.
Obes Rev ; 16(11): 1001-15, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26252230

ABSTRACT

Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5-24.9, 25-29.9, ≥30 kg/m(2)), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow-up were meta-analysed. Compared with normal weight, all-cause mortality HRs were 1.41 (95% CI = 1.26-1.58) for underweight, 0.85 (95% CI = 0.73-0.99) for overweight and 0.74 (95% CI = 0.57-0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR = 1.65 [95% CI = 1.13-2.40]). RR results corroborated primary HR results, with additionally lower infection-related mortality in overweight and obese than in normal-weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.


Subject(s)
Body Mass Index , Frail Elderly/statistics & numerical data , Homes for the Aged/statistics & numerical data , Nursing Homes/statistics & numerical data , Overweight/mortality , Thinness/mortality , Aged , Aged, 80 and over , Female , Humans , Male , Nutritional Physiological Phenomena , Risk Factors
9.
J Med Chem ; 32(5): 957-61, 1989 May.
Article in English | MEDLINE | ID: mdl-2565401

ABSTRACT

Three N-fluoroethyl-substituted (imidazolylphenyl)formamidine derivatives, namely, 2-fluoroethyl (3b), 2,2-difluoroethyl (3c), and 2,2,2-trifluoroethyl (3d), were prepared to test the effect of fluorine substitution on basicity and, then, on H2-antagonist affinity in comparison with the unsubstituted N-ethyl derivative (3a), taken as a model of mifentidine. Imidazolylphenyl isothiocyanate (1), obtained by reaction of 4-(aminophenyl)imidazole with carbon disulfide and ethyl chloroformate, was condensed with the requisite 2-fluoro-substituted ethylamines to give the intermediate thioureas (2b-d). Desulfurization of these thioureas by Raney nickel furnished the desired formamidines (3b-d). Increasing fluorine substitution was found to decrease basicity of the formamidino group substantially (3a, pKa = 8.65; 3b, pKa = 8.12; 3c, pKa = 6.60; 3d, pKa = 6.14), while having a modest effect on the imidazole portion. Affinity at the H2 receptors, evaluated from antagonism of histamine-stimulated chronotropic response on guinea pig atria, increased following fluorine substitution (3a, KB = 177; 3b, KB = 61; 3c, KB = 21; 3d, KB = 7.6). It is concluded that H2-receptor antagonist affinity in the mifentidine series is mostly dependent on the availability of the neutral species. These data support the hypothesis that mifentidine, like cimetidine, acts through the neutral species.


Subject(s)
Histamine H2 Antagonists/pharmacology , Imidazoles/pharmacology , Animals , Guinea Pigs , In Vitro Techniques , Male , Structure-Activity Relationship
10.
J Med Chem ; 33(8): 2108-13, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2374141

ABSTRACT

Amidines (guanidine, formamidine, and acetamidine) were introduced as substitutes for the cationic heads present in atropine, scopolamine, and corresponding quaternary derivatives. Amidine systems are intermediate in structure between tertiary amines and quaternary compounds, at least as regards ionization and electronic properties, but differ from the latter in shape (planar not tetrahedral). They have additional binding opportunities on account of their hydrogen-bond-forming capacity. The effect of the introduction of these cationic heads on the affinity for different muscarinic acetyl choline receptor (m-AcChR) subtypes was investigated in vitro, in binding displacement studies, and in functional tests on isolated organs. All new compounds (3a,b-5a,b) showed high affinity for the m-AcChR considered, comparable or slightly inferior to that of the parent drugs (1a-e). The new amidine derivatives proved effective as spasmolytic agents, with little tendency to cause central effects. However, no separation was achieved of spasmolytic and other untoward effects, like inhibition of salivation. Thus, amidine moieties are effective bioisosteric substitutes for conventional cationic heads present in antimuscarinic agents. Their unusual physical-chemical properties make them useful tools when modulation of pharmacokinetic or pharmacodynamic effects is required.


Subject(s)
Amidines/pharmacology , Atropine Derivatives/pharmacology , Muscarine/antagonists & inhibitors , Scopolamine Derivatives/pharmacology , Amidines/chemical synthesis , Amidines/metabolism , Animals , Atropine Derivatives/chemical synthesis , Atropine Derivatives/metabolism , Cations , Cerebral Cortex/metabolism , Chemical Phenomena , Chemistry , Chemistry, Physical , Electrochemistry , Female , Male , Molecular Structure , Muscle Contraction/drug effects , Myocardium/metabolism , Parasympatholytics/pharmacology , Rats , Rats, Inbred Strains , Receptors, Muscarinic/metabolism , Salivation/drug effects , Scopolamine Derivatives/chemical synthesis , Scopolamine Derivatives/metabolism , Submandibular Gland/metabolism
11.
J Med Chem ; 27(3): 380-6, 1984 Mar.
Article in English | MEDLINE | ID: mdl-6142117

ABSTRACT

Structure-activity considerations of N alpha-guanylhistamine, the first compound found with detectable H2-antagonist activity, led to the synthesis of a series of conformationally rigid guanylhistamine analogues, namely, (imidazolylphenyl)guanidines, imidazolylbenzamidines, and (imidazolylphenyl)formamidines. It was found that in the guanidine and benzamidine classes, the meta-substituted derivatives (3, 4, 7, and 8) possessed H2-antagonist activity, whereas in the class of formamidines, only the para-substituted derivative 10 was found active. A subsequent increase in the size of the substituent at the formamidino group of 10 led to compounds (15-20) of high H2-antagonist affinity, which was related to the gastric antisecretory effect. Members of this structurally novel class of H2 antagonists were 20- to 50-fold more potent than cimetidine both "in vitro" and "in vivo". Structure-activity relationships are discussed in terms of ionization properties, partitioning behavior, conformational aspects of the selected compound 17, and of possible modes of interaction with the histamine H2 receptor. It was found that the formamidine moiety was an important structural feature and that H2-antagonist activity requires correct steric and electronic properties. Compound 17 (DA 4577), owing to its pharmacological profile and demonstrated safety in animals, was selected to be clinically investigated.


Subject(s)
Amidines/analysis , Histamine H2 Antagonists/analysis , Imidazoles/analysis , Amidines/pharmacology , Animals , Cimetidine/analysis , Dogs , Gastric Acid/metabolism , Histamine/analysis , Histamine H2 Antagonists/pharmacology , Imidazoles/pharmacology , Male , Rats , Rats, Inbred Strains , Structure-Activity Relationship
12.
J Med Chem ; 34(6): 1772-6, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1676425

ABSTRACT

The influence of alkyl substitution on the stereoisomerism of the formamidine cation (E,E vs E,Z) of several N-substituted (imidazolylphenyl)formamidines (1-10) was investigated. As (imidazolylphenyl)formamidines having alkyl substituents of more than three carbon atoms bind to H2-receptor preparations in a pseudoirreversible mode causing unsurmountable antagonism, the four isomeric butylformamidines (5-7 and 9) having comparable lipophilic character but different E,E/E,Z composition were investigated in H2-receptor assays to determine quantitatively any difference in their pseudoirreversible inhibitory pattern. It was found that the geometry of the formamidine cation is affected by the steric bulk of the substituent on the formamidine nitrogen. A relationship between the percentage of the E,E conformation of the formamidine cation and degree of pseudoirreversible antagonism was also found. The present studies support the hypothesis that bidentate hydrogen bonding plays an important role in the interaction of (imidazolylphenyl)formamidines with the H2 receptor.


Subject(s)
Amidines/pharmacology , Histamine H2 Antagonists , Amidines/metabolism , Animals , Guinea Pigs , Histamine H2 Antagonists/metabolism , Magnetic Resonance Spectroscopy , Male , Molecular Conformation , Stereoisomerism
13.
Br J Pharmacol ; 100(1): 150-2, 1990 May.
Article in English | MEDLINE | ID: mdl-2372655

ABSTRACT

1. The affinity of a number of derivatives of the muscarinic antagonist, hexocyclium, containing an amidine cationic head, for guinea-pig cardiac and ileal receptors was investigated. 2. All the compounds studied displayed a greater affinity for muscular than for cardiac muscarinic receptors. 3. The 5 fold ileal selectivity of hexocyclium was increased by a number of chemical substitutions. The largest discrimination between receptors (about 200 fold) was found for the formamidine derivative. 4. The selectivity displayed by the hexocyclium derivatives stemmed from a greater decrease in affinity towards cardiac as compared to ileal receptors.


Subject(s)
Muscle, Smooth/metabolism , Parasympatholytics/metabolism , Piperazines/metabolism , Receptors, Muscarinic/metabolism , Animals , Bethanechol Compounds/pharmacology , Binding, Competitive/drug effects , Formamides/pharmacology , Guinea Pigs , Heart/drug effects , Ileum/drug effects , Ileum/metabolism , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Myocardial Contraction/drug effects , Myocardium/metabolism , Parasympatholytics/pharmacology , Piperazines/pharmacology , Receptors, Muscarinic/drug effects
14.
Br J Pharmacol ; 113(3): 711-6, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7532081

ABSTRACT

1. This study describes the in vitro interaction of the muscarinic ligand McNeil-A-343 with two 5-hydroxytryptamine (5-HT) receptor subtypes, the 5-HT4 and 5-HT3 receptors, using functional as well as radioligand binding studies. 2. In the rat oesophageal muscularis mucosae, precontracted with carbachol, McNeil-A-343 was a competitive antagonist (pA2 6.2) of the 5-HT4 receptor which mediates the relaxation induced by 5-HT. The compound per se relaxed the oesophagus at high concentration only (> or = 10 microM), an effect unchanged by desensitization of the 5-HT4 receptor with 10 microM 5-methoxytryptamine. In the same preparation in the absence of tone, McNeil-A-343 displaced the carbachol concentration-response curve to the right, yielding an apparent affinity (pA2) of 4.9 for muscarinic receptors. 3. In the rat isolated superior cervical ganglion preparation, after blockade of muscarinic and nicotinic receptors, McNeil-A-343 caused a concentration-dependent depolarization that was unaffected by 100 nM ondansetron. The concentration-fast depolarization curve to 5-HT, mediated by the 5-HT3 receptor, was displaced to the right by McNeil-A-343, which showed an apparent affinity (pA2) of 4.8 for the 5-HT3 subtype. 4. In binding studies, McNeil-A-343 recognized a single population of 5-HT4 receptors in pig caudate nucleus, with a pKI of 5.9. The binding affinity of McNeil-A-343 for 5-HT3 receptors in NG 108-15 cells was approximately four times lower (pKI 5.3). Binding affinities (pKI) for muscarinic receptor subtypes in rat tissues were 5.3 (M1, cortex), 5.2 (M2, heart) and 4.9 (M3, submandibular glands), respectively. 5. McNeil-A-343 is an antagonist at 5-HT4 and 5-HT3 receptors; the interaction of the compound with these receptor subtypes (notably the 5-HT4) occurs in a range of concentrations which generally overlaps that relevant to the interaction with muscarinic receptors.


Subject(s)
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride/pharmacology , Receptors, Serotonin/drug effects , Serotonin Antagonists/pharmacology , (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride/metabolism , Animals , Carbachol/pharmacology , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Muscle Contraction/drug effects , Rats , Rats, Sprague-Dawley , Receptors, Serotonin/metabolism
15.
Life Sci ; 47(15): PL55-8, 1990.
Article in English | MEDLINE | ID: mdl-2233131

ABSTRACT

The study reports the functional affinity of an amidino derivative of pirenzepine, guanylpirenzepine, for muscarinic receptors mediating relaxation of rat duodenum, inhibition of rabbit vas deferens twitch contraction (both receptors previously classified as M1), guinea pig negative inotropism (M2) and ileal contraction (M3). Unlike pirenzepine, guanylpirenzepine discriminated between duodenum and vas deferens receptors, with a 30-fold greater affinity for the former subtype. The unique selectivity pattern of guanylpirenzepine (duodenum greater than vas deferens greater than ileum greater than atrium) renders it a promising tool for the classification of muscarinic receptor subtypes.


Subject(s)
Guanine/analogs & derivatives , Muscarine/antagonists & inhibitors , Pirenzepine/analogs & derivatives , Receptors, Muscarinic/physiology , Animals , Atrial Function , Duodenum/physiology , Guanine/metabolism , Guinea Pigs , Ileum/physiology , Male , Muscarinic Antagonists , Muscle Relaxation/drug effects , Muscle Relaxation/physiology , Pirenzepine/metabolism , Rabbits , Rats , Rats, Inbred Strains , Vas Deferens/physiology
16.
Arch Gerontol Geriatr ; 15 Suppl 1: 27-35, 1992.
Article in English | MEDLINE | ID: mdl-18647674

ABSTRACT

It is well-known that bone volume decreases with age both in normal subjects and particularly in osteoporotic patients. It is not well demonstrated, however, whether bone loss is associated with changes in the composition of bone tissue and especially with altered concentration of mineral elements. To verify whether calcium density changes with aging, autoptic specimens, of iliac crest trabecular bone from 20 normal subjects between 21 and 66 years, 10 males and 10 females were analyzed by using a new method which allows the measurement of calcium density in a non-destructive way, on entire histologic sections of the bone. Bone specimens were embedded in araidite and tissue sections, about 3 microm thick and 4x4 mm size, were mounted onto polyvinyl acetate films and analyzed by PIXE (proton induced X-ray emission) using the CISE setup for calcium content determination. The same bone tissue sections were then mounted on glass slides, stained with the Von Kossa method and the volume of calcified bone was measured with a semiautomatic image analyzer (Videoplan). 3 to 4 sections from each subject were analyzed and the values of calcium concentration were derived in microg/microl. Similar values of calcium density were found in males and females (535.6+77.1 and 539.2+74.1 microg/microl, respectively). No significant correlation between calcium density and age was observed either in all cases (r=0.0925) or in males (r=-0.0687) and in females (r=0.2676) separately. The unchanged calcium density during aging obtained by combining PIXE and histomorphometric techniques demonstrates that the skeletal calcium reduction observed in old age and probably during osteoporosis, is mainly due to the decrease of bone volume.

17.
Farmaco ; 46(1): 45-62, 1991 Jan.
Article in English | MEDLINE | ID: mdl-2054041

ABSTRACT

The synthesis of lipophylic derivatives of the amino acid residues of the CCK-8 fragment is described. According to "in vitro" binding studies and functional test, nearly all the compounds behaves as CCK-antagonists; moreover some compounds are able to interact differentially with CCK-A and CCK-B receptor subtype. In particular, compounds 2c, 2g, and 2h possess a high affinity for the CCK-A receptor subtype coupled with a low affinity for the CCK-B subtype. This results in an interesting selectivity profile. However, the same compounds are not able to antagonize the effects exerted by CCK-itself, when tested in "in vivo" assays.


Subject(s)
Cholecystokinin/antagonists & inhibitors , Pyrazines/chemical synthesis , Receptors, Cholecystokinin/antagonists & inhibitors , Sincalide/analogs & derivatives , Vinyl Compounds/chemical synthesis , Amino Acid Sequence , Animals , Brain Chemistry/drug effects , Female , Gallbladder/drug effects , Guinea Pigs , In Vitro Techniques , Male , Mice , Molecular Sequence Data , Pancreas/drug effects , Pancreas/metabolism , Pyrazines/pharmacology , Pyrazines/therapeutic use , Sincalide/pharmacology , Thiones/chemical synthesis , Thiones/pharmacology , Thiones/therapeutic use , Thiophenes , Vinyl Compounds/pharmacology , Vinyl Compounds/therapeutic use
18.
Eur J Drug Metab Pharmacokinet ; 19(3): 179-83, 1994.
Article in English | MEDLINE | ID: mdl-7867659

ABSTRACT

Alzheimer disease (AD) is a neurodegenerative disorder lacking an effective therapy. The etiology is controversial and among different drug strategies, the cholinergic approach has gained great interest owing to biochemical and pharmacological evidence of the crucial role of acetylcholine in cognitive functions. Several attempts exploiting the boosting of the cholinergic system are currently under way. Inhibitors of the acetylcholinesterase enzyme sustain the availability of the natural transmitter by limiting its removal from the synapse. In a different approach, exogenous agonists may substitute acetylcholine itself. In this way the issue of the extensive cholinergic cell loss occurring in AD and leading to a reduction of cholinergic functions, could be advantageously bypassed. Moreover the discovery of different muscarinic receptor subtypes, most notably the M1 subtype as that involved in the postsynaptic transmission, has offered new opportunities to face the problem in a very specific way. In this line of research, we have now identified BIMC 182 as a new functionally selective M1 agonist. Whereas its affinity for the different receptor subtypes is almost similar (radioreceptor binding), its functional selectivity is pointed out by specific "in vitro" models. BIMC 182 behaves as a full agonist at M1 (rat superior cervical ganglion, pD2 4.8) and as a partial agonist at M2 and M3 sites (g.p. heart pD2 = 5.4 and g.p. ileum pD2 = 4.5). The agonist profile is further confirmed in hm1 transfected CHO cells where the compound stimulates PI turnover. BIMC 182 penetrates well the brain as shown by the increase in the energy of the low frequency band (theta waves) in the cortical EEG of rabbits (3 mg/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Alzheimer Disease/drug therapy , Muscarinic Agonists/pharmacology , Animals , Brain/drug effects , CHO Cells , Cricetinae , Female , Learning/drug effects , Male , Muscarinic Agonists/metabolism , Muscarinic Agonists/therapeutic use , Rabbits , Rats , Receptors, Muscarinic/metabolism
19.
Neurology ; 78(19): 1507-11, 2012 May 08.
Article in English | MEDLINE | ID: mdl-22539572

ABSTRACT

OBJECTIVE: Recent literature suggests that diabetes is a risk factor for Parkinson disease (PD). We investigated the clinical features of patients with idiopathic PD (IPD) in whom the onset of diabetes came first. METHODS: We designed a case-control study. From the cohort of all new patients with IPD free of vascular disease (n = 783) admitted and evaluated at our institute over a 3-year period (2007-2010), we included all the patients with a diagnosis of diabetes prior to PD onset (n = 89) and a control group (n = 89) matched (1:1) for gender, body mass index (± 1 kg/m(2)), and duration of PD (± 1 year). The Unified Parkinson's Disease Rating Scale (UPDRS) motor score was the primary endpoint. RESULTS: At study entry, patients with diabetes were similar to controls in terms of most demographic, lifestyle, and general medical features with exception of statins (18% vs 3.4%; p = 0.003). However, diabetes was associated with higher UPDRS motor (22.3 ± 9.0 vs 19.3 ± 7.9; p = 0.019) and activities of daily living (9.7 ± 5.1 vs 8.3 ± 4.3; p = 0.049) scores, more severe Hoehn & Yahr staging (p = 0.009), and higher treatment doses of levodopa (mg/day, 448 ± 265 vs 300 ± 213; p < 0.0001; mg/kg/day, 5.8 ± 4.0 vs 3.8 ± 2.9; p < 0.0001). CONCLUSIONS: Onset of diabetes before the onset of PD appears to be a risk factor for more severe PD symptoms. These findings support the hypothesis that diabetes has a role in the etiopathogenesis of PD. Neurologists should be aware of the potential impact of diabetes on overall PD management.


Subject(s)
Diabetes Mellitus, Type 2/complications , Parkinson Disease/complications , Parkinson Disease/diagnosis , Aged , Aged, 80 and over , Case-Control Studies , Diabetes Mellitus, Type 2/physiopathology , Disease Progression , Female , Humans , Male , Middle Aged , Parkinson Disease/physiopathology , Risk Factors , Severity of Illness Index
20.
J Nutr Health Aging ; 14(1): 16-22, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20082049

ABSTRACT

OBJECTIVES: To investigate if the use of estimated height (EH) by currently available prediction formulas might affect the screening and outcome prediction attitudes of both the Mini Nutritional Assessment (MNA) and its short-form version (MNA-SF). DESIGN: A 6-month observational study. SETTING: Two long-term cares of the province of Como. PARTICIPANTS: 266 resident elderly (102 men, 164 women; mean age +/- SD: 80.4 +/- 8.6 years). MEASUREMENTS: Subjects were studied by anthropometry (weight, standing height, knee-height, arm and calf circumferences, triceps skinfold) and biochemistry (albumin and prealbumin). Nutritional status was assessed using both MNA and MNA-SF. At 6 months, major outcome were: death, infections and bedsores. RESULTS: In overall population, prediction formulas significantly underestimated real height. The bias by Italian-specific equation was higher than that by nationally-representative formulas for white Americans. The use of EHs produced significant differences in body mass index (BMI) but these did not affect nutritional status scoring by MNA and MNA-SF (r > or =0.99, p < 0.0001). Cohen's kappa statistic also showed an almost perfect concordance (kappa > 0.9). Moreover, similar degrees of correlation were found between nutritional parameters and both MNA and MNA-SF scores by BMI from SH and EHs. After 6 months, major complications occurred in twenty-eight patients (11.6%). The use EHs did not affect the distribution of events among MNA and MNA-SF nutritional classes. CONCLUSION: In Italian elderly, height prediction by nationally representative equations for white Americans should be preferred to that by ethnic-specifc formula. However, the use of both models does not seem to affect nutritional screening and outcome prediction by MNA and MNA-SF.


Subject(s)
Geriatric Assessment/methods , Knee/anatomy & histology , Nutrition Assessment , Nutritional Status , Serum Albumin/analysis , Aged , Aged, 80 and over , Anthropometry/methods , Body Height , Body Mass Index , Ethnicity , Female , Health Status , Health Status Indicators , Homes for the Aged , Humans , Infections/epidemiology , Italy , Male , Malnutrition/diagnosis , Nursing Homes , Predictive Value of Tests , Pressure Ulcer/epidemiology , White People
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