Mesenchymal stem cells support dorsal root ganglion neurons survival by inhibiting the metalloproteinase pathway.

The positive effect of adult undifferentiated mesenchymal stem cells (MSCs) on neuronal survival has already been reported, although the mechanisms by which MSCs exert their effect are still a matter of debate. Here we have demonstrated that MSCs are able to prolong the survival of dorsal root ganglion (DRG) neurons mainly by inhibiting some proteolytic enzymes, and in particular the pathway of metalloproteinases (MMPs), a family of proteins that are involved in many neuronal processes, including survival. The inhibition of MMPs was both direct, by acting on MT-MMP1, and indirect, by acting on those proteins that regulate MMPs' activation, such as Timp-1 and Sparc. The importance of the MMPs' down-regulation for neuronal survival was also demonstrated by using N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycyl hydroxamic acid (NNGH), a wide range inhibitor of metalloproteinases, which was able to increase the survival of DRG neurons in a significant manner. The down-regulation of MMPs, obtained both by MSC contact and by chemical inhibition, led to the inactivation of caspase 3, the executor of apoptotic death in DRG neurons cultured alone, while caspase 7 was found to be irrelevant for the apoptotic process. The capacity of MSCs to prevent apoptosis mainly by inactivating the metalloproteinase pathway is an important finding that sheds light on MSCs' mechanism of action, making undifferentiated MSCs a promising tool for the treatment of many different neurodegenerative pathologies.

The effects of an early developmental mother-child intervention program on neurodevelopment outcome in very low birth weight infants: a pilot study.

BACKGROUND: Several studies report increased minor neurodevelopment dysfunctions in children born very low birth weight (VLBW). Usefulness of preventive early intervention programs to improve neurodevelopment outcome of VLBW infants is still under investigation. AIMS: To evaluate the effects of an early post-discharge developmental mother-child intervention program on neurodevelopment outcome at 36 months in VLBW infants. STUDY DESIGN: Prospective study. SUBJECTS: 36 VLBW infants ([mean (S.D.)] birthweight=864 g (204 g); gestational age=27.9 weeks (2.4 weeks)), consecutively born January-August 2001, randomized in intervention and control groups. OUTCOME MEASURES: Neurodevelopment assessment at 36 months of chronological age with use of the Griffiths Mental Development Scale and related subscales. RESULTS: At 36 months of chronological age, as compared to controls, children in intervention group exhibited higher scores in personal-social subscales ([mean (S.D.)]=101.4 (9.3) vs. 92.9 (12.1), P=0.02), eye-hand coordination (92.7 (4.5) vs. 87.1 (9.9), P=0.041), practical reasoning (98.6 (8.2) vs. 89.4 (10.1), P=0.01). Development Scale were 97.6 (5.5) and 92.4 (9.9), respectively, in intervention and control groups (P=0.074). CONCLUSIONS: Early post-discharge developmental mother-child intervention program may have a positive effect on later neurodevelopment outcome of VLBW children.

Blood glucose monitoring in gestational diabetes mellitus: 1- versus 2-h blood glucose determinations.

Gestational diabetes mellitus is a common disorder of pregnancy affecting 3-5% of pregnant women. Although significant controversy exists regarding its diagnosis and treatment, macrosomia has been consistently associated with maternal hyperglycemia. Numerous studies have addressed different approaches to monitoring blood glucose levels, but data on the ideal timing for postprandial determinations are scarce. This article reviews current recommendations and recent findings on the implications of 1- versus 2-h blood glucose determinations in pregnant women with gestational diabetes mellitus. Preliminary studies have shown a statistically significant reduction in macrosomia and decreased need for emergency Cesarean section among women monitored 1 h after meals. Until larger studies confirm these benefits, compliance is of the utmost importance for successful treatment. Therefore, patient preferences should be considered in planning a monitoring strategy.

Comparison of A-mode ultrasound and computed tomography: detection of secretion in maxillary and frontal sinuses in ventilated patients.

OBJECTIVE: To study the accuracy of A-mode ultrasonography (A-MU) in detecting secretion in maxillary and frontal sinuses in critically ill, intubated patients undergoing mechanical ventilation. DESIGN: Open study in mechanically ventilated, comatose patients. SETTING: Medical-surgical intensive care unit in the General Hospital of Rovigo. PATIENTS: 50 consecutive, mechanically ventilated, critically ill patients. All patients were in a coma and needed cerebral computed tomography (CT) for a diagnosis. MEASUREMENTS AND RESULTS: The A-MU technique gave 100 images of maxillary and frontal sinuses. The images were read blindly and classified into five categories: definitely normal, definitely abnormal, probably normal, questionable, and probably abnormal. CT findings were considered to be the "gold standard". The specificity of echo images varied from 72 to 98% and the sensitivity from 63 to 86% for maxillary sinuses. For frontal sinuses, the specificity varied from 96 to 99% and the sensitivity from 14 to 57%. The area under the receiver-operating characteristic curve was found to be 0.89 and 0.76 for maxillary and frontal sinuses, respectively. CONCLUSIONS: The A-MU technique is an accurate tool for detecting secretion in the maxillary sinuses in intubated patients. More investigations are necessary in order to evaluate its usefulness in the frontal sinuses.

[Well-differentiated acinic cell carcinoma of the parotid]. / Carcinoma a cellule aciniche bene differenziato della parotide.

Well-differentiated acinic-cell carcinoma of parotid gland. The authors report a case of well-differentiated acinic-cell carcinoma of the parotid gland with an important lymphoid component, whereas in the aspiration a diagnosis of adenolymphoma was made. In our case cytologic examination showed an abundant cellularity, consisting mostly of lymphocytes. Epithelial elements were monomorphic and had a discrete quantity of amphophilic, granular cytoplasm. Such structures sometimes appeared to be in continuity with ductal-type formations, suggesting normal glandular acini of the serous type. Elements oncocytes-like with abundant, basophilic granular cytoplasm were seen also. These cells oncocytes-like, the rich lymphoid component and the presence of little amorphous debris, suggested an adenolymphoma. The differential diagnosis between ACC, adenocarcinoma, and lymphonodal metastasis did not show problems because of the lacking of the cytological atipie. Histologic examination of the surgical specimen did not show problems of differential diagnosis. Morphologic patterns included acinar, tubuloductal, microcystic and follicular structures. Periodic acid Schiff positivity, resistant to diastase, was noted in most serous cells. An acid alcian blue stain was negative within the cell cytoplasm but moderately positive in the microcystic cavities. The final histologic diagnosis was that of a well-differentiated acinic cell carcinoma with a rich lymphoid component.

A novel class of cholinergic agents structurally related to 2-morpholinol.

A series of esters and ethers of N-alkylmorpholin-2-ols, and their methiodides, which can be considered cyclic analogues of acetylcholine, were synthesized. The amines were obtained by acylation or etherification of morpholinols with the appropriate acyl chlorides and alcohols. All compounds were tested for their ability to interact with the muscarinic receptor M2 (guinea-pig atria) or M3 (rat ileum and urinary bladder) subtype. Some compounds, although endowed with relatively low potency, proved interesting for their organ selectivity. Some considerations on the structure-activity relationship are made and the results obtained with reference agonists and antagonists are also shown.

Synthesis of C-2 and C-4 deuterium-labeled estradiol-17 beta.

Estradiol-17 beta labeled with deuterium in the positions 2 or 4 can be prepared from 2-chloromercurio-1,3,5(10)-estratriene-3,17 beta-diol 3-methyl ether 17-acetate or 4-chloromercurio-1,3,5(10)-estratriene-3,17 beta-diol, respectively, in refluxing CH3COO(2)H/(2)H2O. The same reaction performed on 4-acetoxymercurio-1,3,5(10)-estratriene-3,17 beta-diol afforded 2,4-dideuterio-estradiol-17 beta in good yields.