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C Simone

Publications and source records attributed to C Simone.

At least 37 records · Page 2Linked to original sources

Acetylcholinesterase and butyrylcholinesterase activity in the human term placenta: implications for fetal cocaine exposure.

The characterization of the enzymes responsible for drug metabolism in the human placenta is of great importance in determining the possible role the placenta plays in protecting the fetus from potentially fetotoxic drugs. We speculate that the placenta metabolizes cocaine, serving to protect the fetus from the drug's ill effects. Cholinesterase, the principle enzyme that metabolizes cocaine, has been hypothesized to be present yet is not well characterized in the human placenta. The purpose of this study was to quantify human placental acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Human placentas were obtained from elective cesarean sections, and several lobules were thoroughly perfused with cold buffer to ensure minimal contamination from erythrocyte AChE. Subcellular fractions were then prepared from these lobules by using standard differential centrifugation techniques. Microsomes and cytosol were assayed for AChE and BChE activity by using a spectrophotometric assay. BChE activity was found in the cytosolic fraction of the placental villous tissue, whereas AChE activity was measured in the microsomal fraction. By demonstrating that BChE activity is present in human term placenta we have shown that this organ has the capacity to metabolize cocaine and may therefore serve as a metabolic barrier to fetal exposure to cocaine.

Acetylcholinesterase↗

Local blood-brain barrier in the newborn rabbit: postnatal changes in alpha-aminoisobutyric acid transfer within medulla, cortex, and selected brain areas.

Postnatal changes in local permeability of the blood-brain barrier to an inert neutral amino acid (alpha-[14C]-aminoisobutyric acid) were investigated in 25 rabbits. The local transfer constant (K) for this tracer was measured with quantitative autoradiographic techniques at postnatal ages of 1, 3, 8, and 17 days, and adult. In adults, the amino acid penetrated the blood-brain barrier poorly in most regions examined (K less than 1 microliter.g-1.min-1) except within and in proximity to structures with a relatively leaky blood-brain barrier such as area postrema and choroid plexus. The rate of tracer entry into "impermeable" regions was seven- to 10-fold greater in 1-day-old rabbits than adults and not dependent on active transport. In young animals, there was a pronounced regional variation in K with the lowest values occurring in white matter and the highest in gray matter such as cerebral cortex, posterior thalamus, and hippocampus. During postnatal development, K decreased (p less than 0.01) with most regions having values near those of adults by 17 days of age. The results indicate that the blood-brain barrier of the newborn rabbit is relatively leaky to a small hydrophilic nonelectrolyte with a distribution that is heterogeneous regionally. Irrespective of age, such blood-borne substances can accumulate in certain brain areas considered to have impermeable vessels (e.g., nucleus tractus solitarii).

Aging↗

Toxicity of WR-2721 administered in single and multiple doses.

Two hundred forty-three patients have received WR-2721 in Phase I-II studies. Separate studies were conducted in which patients with advanced malignancies received WR-2721 before single or multiple doses of radiotherapy or in single doses prior to cyclophosphamide, nitrogen mustard or cis-platinum. Single doses were escalated from 25 to 1330 mg/m2. An Acceptable Tolerated Dose (ATD) of 740 mg/m2 infused in 15 minutes has been established and is currently used in Phase II studies. Significant persistent hypotension (greater than 20 torr systolic) as a dose-limiting toxicity has occurred in 5% of patients in the single dose study. Fifty-five patients have been entered in the multiple dose trial. Dose levels of 340 mg/m2, four times a week for three weeks, and 250 mg/m2, four times a week for six weeks have been reached. There were five idiosynchratic reactions (fever, chills, rash, hypotension), one of which was severe. Some patients withdrew from the multiple dose study because of vomiting after each injection, or fear. No deaths nor any long-term untoward effects were observed. There is no suggestion of tumor protection.

Amifostine↗

Osteosclerosis in leprosy.

The literature contains little reference to the phenomenon of osteosclerosis in leprosy. The aim of the authors' investigations was to determine: a) the incidence of osteosclerosis as part of the radiographic picture in the distal extremities of the limbs; b) the pathological substratum; c) the possible clinical significance. The research was carried out on 233 leprosy patients at the Colonia Hanseniana di Gioia del Colle (Bari). The authors examined 260 radiographs of the hands and 1310 radiographs of the feet. A number of biopsy samples of bone were taken from four patients and examined by means of microradiography using ultraviolet fluorescent light and also by historadiography. The basic radiographic features indicative of osteosclerosis were: a) reactive osteosclerosis; b) sclerosing periostosis; c) massive osteosclerosis. The authors observed a preponderance of osteosclerosis in the bones of the first digital ray, both in the phalanges and metatarsals or metacarpals. The sesamoid bones were affected more commonly in those of the first digit than those of the fifth. The radiographic findings were confirmed microscopically. It is difficult to assess the possible clinical significance because of the transient nature of the osteosclerosis in the evolution of the lepromatous lesions with time.

Adult↗

The transfer, of cocaethylene across the human term placental cotyledon perfused in vitro.

Cocaethylene is produced by transesterification of cocaine in the presence of ethanol, and there is evidence that it is more neurotoxic than cocaine. Because many women of reproductive age use cocaine and because many cocaine users also consume alcohol, the fetal toxicology of cocaethylene is of great concern. At the present time the placental transfer of cocaethylene has not been fully characterized. The objective of this article was to measure the transfer of cocaethylene across the human term placenta. The transfer of cocaethylene was measured using the in vitro dual perfusion of the human term placental cotyledon. Using a "closed-circuit" design, the extraction fraction of cocaethylene was measured to be 0.009 microgram/mL.min-1 and the transfer fraction was measured to be 0.013 microgram/mL.min-1, suggesting that the placental tissue retained some of the administered dose. Using an "open circuit" design, the clearance of the compound by the placenta was found to be 78 +/- 14% that of antipyrine clearance. The metabolism of cocaethylene by the perfused placental cotyledon was also measured using an "open circuit" design and was found to be negligible. These results indicate that the placenta does not serve as a significant physical or metabolic barrier to cocaethylene transfer from mother to child. As compared to previously reported results, the transfer of this compound across the human placenta is similar to that of cocaine. Variability in placental handling of cocaethylene may therefore determine fetal exposure to this compound.

Cocaine↗

Quality assessment of economic evaluations in selected pharmacy, medical, and health economics journals.

OBJECTIVE: To assess and compare the quality of economic studies in selected pharmacy, medical, and health economics journals. DATA SOURCES: DICP The Annals of Pharmacotherapy, American Journal of Hospital Pharmacy, Hospital Pharmacy, New England Journal of Medicine, Medical Care, Journal of the American Medical Association, PharmacoEconomics, International Journal of Technology Assessment in Health Care, and Journal of Health Economics using MEDLINE, EMBASE, and International Pharmaceutical Abstracts. Search terms included "economic," "cost," and "cost analysis." STUDY SELECTION: Reviewers appraised abstracts to identify original research published during 1989-1993 comparing costs and outcomes between drugs, treatments, and/or services. Initially, 123 articles met criteria; 16 were inappropriate, 17 were randomized out, and 90 (73%) were used (30/group). DATA EXTRACTION: Quality was assessed using a 13-item checklist. Interrater reliability was 0.91 (p < 0.05) for 9 raters, test-retest reliability was 0.94 (p < 0.001). DATA SYNTHESIS: A 2-way ANOVA, with overall quality scores as a dependent variable with journal type and year as independent variables, was significant (F = 2.79, p = 0.002, r2 = 0.34), with no significant interaction (F = 0.71, p = 0.68) or time effect (F = 0.70, p = 0.60). Journal types differed; pharmacy journals scored significantly lower (chi 2 = 53.89, df = 2, p < 0.001). Items rated adequate (i.e., correct or acceptable) increased over time (chi 2 = 21.18, df = 4, p < 0.001). Ethical issues and study perspective most needed improvement. CONCLUSIONS: Article quality for all journal types increased over time nonsignificantly; health economics journals scored highest, then medical journals, with pharmacy journals significantly lower (and having the highest standard deviation). We recommend that authors and reviewers pay closer attention to study perspective and ethical implications.

Economics, Pharmaceutical↗

Unilateral lung volume reduction in preparation for contralateral pneumonectomy.

A case of staged trans-sternal unilateral lung volume reduction (LVR) on the right followed by contralateral pneumonectomy for a locally advanced left lung malignancy is presented. The predicted symptomatic and functional benefit offered by LVR was felt to be necessary before the removal of the left lung. The patient, a 50-year-old male, with a history of chronic air flow limitation secondary to bullous emphysema, underwent a left pneumonectomy six weeks following a right LVR procedure for poor pulmonary function secondary to generalized emphysema. On admission, forced expiratory volume in 1 s (FEV1) was 1.37 L, 47% of predicted with an FEV1/forced vital capacity of 56%. Five weeks after the unilateral LVR, the patient's FEV1 was 1.85 L, and one year postdischarge from hospital, FEV1 was 0.9 L. One year after discharge, the patient did not require oxygen support, and was active and free of malignant disease.

Carcinoma, Non-Small-Cell Lung↗

[Baropodometric walking analysis in healthy elderly and in arthritic patients before and after knee prosthesis implantation].

Standing and walking are complex activities which require integral skeletal-muscular and central nervous systems. Body is usually, evenly distributed between both the lower limbs with 40% on the ball of the foot and 60% on the heel, therefore, the body's centre of gravity falls between the feet in correspondence to Chopart's articulation. Some diseases can influence standing and walking including cardiovascular diseases (chronic edema, claudication, cardiopathies etc.) neurosensorial ones (cataract, Menière's disease, Parkinson's disease etc.) and orthopedic ones (kyphosis, scoliosis, hallux valgus, metatarsalgia, osteoarthritis etc.). In this study arthritis was considered the main cause of changes in posture and deambulation. An electric baropodometer with a modular platform 240 cm long and 40 cm wide was used which provided the pressure information for each in three distinct phases: static, dynamic and postural Baropodometric step analysis was performed on ten healthy, elderly subjects and ten elderly subjects with arthritis of the knee. The latter group was evaluated both pre- and post prosthetic knee surgery. The data revealed that the ten healthy subjects with arthritis who, prior to surgery presented unequal weight distribution on the diseased side which was slowly redistributed after surgery.

Age Factors↗

[Effect of glutaraldehyde on the species-specific antigenicity of xenogeneic cartilage].

Present results showed that an extract of xenogeneic cartilage may inhibit the complement activity of human serum, while an extract of xenogeneic cartilage treated with glutaraldehyde may enhance this effect. This finding suggested that treatment with glutaraldehyde does not decrease species-specific antigenicity of xenogeneic cartilage.

Aldehydes↗

[Species-specific antigenicity of xenogeneic bone treated with glutaraldehyde].

Present results showed that an extract of xenogeneic bone may inhibit the complement activity of some human sera, while an extract of xenogeneic bone treated with glutaraldehyde may show a lower inhibiting effect. This finding suggested that a preventive treatment in vitro with glutaraldehyde significantly decreases species-specific antigenicity of bone tissue.

Aldehydes↗