1p36 deletion syndrome: Review and mapping with further characterization of the phenotype,a new cohort of 86 patients

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype–phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.     

Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis

It has been proposed that the initial event of sodium retention in cirrhosis is a peripheral arteriolar vasodilation causing underfilling of the arterial vascular compartment and stimulation of the renin-aldosterone and sympathetic nervous systems. To test this hypothesis, systolic blood pressure, sodium balance and urinary excretion of sodium and aldosterone were sequentially measured in 13 conscious spontaneously hypertensive rats submitted to a cirrhosis induction program with carbon tetrachloride and phenobarbital and in 14 control hypertensive animals. No significant differences were found between control and cirrhotic rats in any of the measured parameters during the first 7 wk of the study. The eighth week sodium retention developed in cirrhotic rats as indicated by a positive sodium balance and a marked decrease of sodium excretion. At the same time a significant reduction in systolic blood pressure and a great increase in urinary excretion of aldosterone were detected. These changes were more marked the ninth week of the study. In cirrhotic rats there was a highly significant direct correlation between systolic blood pressure and urinary sodium excretion. Postmortem examination showed a histological picture of cirrhosis in all animals given carbon tetrachloride and ascites in six of them. These results indicate that the onset of hyperaldosteronism and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis is chronologically related to a significant decrease in arterial pressure, thus supporting the "peripheral arterial vasodilation hypothesis" of ascites.     

Original removing technique of the kidneys for transplantation. An experimental study (author's transl)]

The depicted procedure minimizes the hazards of aggressive manipulations, and excludes any possibility of so-called "warm ischaemia". The kidneys are flushed out in situ with cool pulsatile perfusion through an aortic cannula. Kidneys, aorta and inferior vena cava are then removed en-bloc without interrupting the perfusion, and preserved in Collins' solution at 4 degrees C. After a 6 to 19 hour storage time, one of the kidneys is transplanted on another dog, while the second one is submitted to histological examination. Nine transplantations were carried out, followed in 7 cases with a most satisfactory diuresis resuming, and with urinary ionic levels, as well as daily urea output, normalization within 48 hours. Histologic examination showed an unaffected glomerular apparatus, but some mild tubular lesions.     

Essai d'information sur les drogues en milieu scolaire genevois

Summary This compulsory information is given to students of 12 th grade (14 – 15 years). A film is shown which is followed by a discussion between the students of each class and a doctor of the Health Department who is specialized in drug prevention.Teachers and parents are also informed in the same way.The efficiency of this method will have to be proved in the future.

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Unterrichtsversuch über Drogen in Sekundarschulen in Genf

Zusammenfassung Dieser obligatorische Unterricht findet für Schüler vom 12. Schuljahr (14 – 15 Jahre alt) statt.Ein Film und eine nachfolgende Diskussion zwischen Schülern und Spezialistärzten der Jugend-und Gesundheitsabteilung sind dafür gebraucht werden. Die Lehrer der Sekundarschulen und die Eltern sind gleichfalls unterrichtet.Die Wirksamkeit dieser Präventiverziehung wird noch zu bestimmen sein.

     

Severe obstetric complications nescessitating hospitalization and intensive care: a ten year retrospective study

OBJECTIVES: To assess the serious maternal morbidity during pregnancy, delivery and post partum, which led to an hospitalization in a medical or surgical intensive care unit. STUDY DESIGN: A Retrospective study was carried out on a period of ten years, from July 1986 to July 1996, in the University Teaching Hospital of Besan?on. PATIENTS: The criterions of inclusion come from the definition of the serious maternal morbidity decided by the Inserm: any admission of a pregnant woman in a medical or surgical intensive care unit in the 42 days of the post-partum, whatever the term of the pregnancy and the type of the post-partum, extra uterine pregnancy, spontaneous miscarriage and medical or voluntary abortion. METHODS: Forty-six patient's medical file hospitalized in a medical or surgical intensive care unit between July, 1st 1986 and July, 31st 1996, have been studied. RESULTS: The analysis of the cause underline the gravity of the pathologies handled with young patients and initially healthy, the short length of controlled ventilation and hospitalization, the avoidability of great number of transfer in an intensive care unit, and the lack of hospitalization due to anaesthesia. The frequency of hospitalisation in an intensive care unit during and after the pregnancy was estimated at 0.17% of lives births. CONCLUSION: The serious maternal morbidity could be an indicator of the quality of the obstetrics cares which would complete the study of the maternal mortality. The potential gravity of the complication of the pregnancy and the delivery require better care of this patients.     

Investigation of the in vitro and ex vivo acetylcholinesterase and antioxidant activities of traditionally used Lycopodium species from South America on alkaloid extracts

Ethnopharmacological relevance

The study was aimed at evaluating medicinal and therapeutic potentials of two Lycopodiaceae species, Lycopodium clavatum (L.) and Lycopodium thyoides (Humb. & Bonpl. ex Willd), both used in South American folk medicine for central nervous system conditions. Alkaloid extracts were evaluated for chemical characterization, acetylcholinesterase and antioxidant activities.

Materials and methods

The alkaloid extracts obtained by alkaline extraction were determined for each species by GC/MS examination. The evaluation of the anticholinesterase and the antioxidant activities of the extracts were tested by determining in vitro and ex vivo models. Effects on acetylcholinesterase (AChE) were tested in vitro using rat brain homogenates and ex vivo after a single administration (25, 10 and 1 mg/kg i.p.) of the alkaloid extracts in mice. The in vitro antioxidant effects were tested for the 2-deoxyribose degradation, nitric oxide (NO) interaction, 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and total reactive antioxidant potential (TRAP). After an acute administration (25 and 10 mg/kg i.p.) of the extracts in middle-aged (12 months) mice, the antioxidant effects were estimated through the thiobarbituric acid reactive substances test (TBARS), and the antioxidant enzymes activities for catalase (CAT) and superoxide dismutase (SOD) were measured.

Results

AChE activity was inhibited in vitro by the alkaloid-enriched extracts of both Lycopodium species in a dose and time-dependent manner in rat cortex, striatum and hippocampus. A significant inhibition was also observed in areas of the brain after acute administration of extracts, as well as decreased lipid peroxidation and increased CAT activity in the cortex, hippocampus and cerebellum. A moderate antioxidant activity was observed in vitro for the extracts. Chemically, the main alkaloids found for the two species were lycopodine and acetyldihidrolycopodine.

Conclusion

This study showed that the biological properties of the folk medicinal plants Lycopodium clavatum and Lycopodium thyoides include AChE inhibitory activity and antioxidant effects, two possible mechanisms of action in Alzheimer's related processes.     

Enhancing the Buccal Mucosal Delivery of Peptide and Protein Therapeutics

Pharmaceutical Research - With continuing advances in biotechnology and genetic engineering, there has been a dramatic increase in the availability of new biomacromolecules, such as peptides and...     

HPV circulating tumor DNA to monitor the efficacy of anti‐PD‐1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report

Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV‐associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD‐1 immune checkpoint inhibitor, demonstrated significant efficacy as single‐agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single‐agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof‐of‐concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents.     

Anti-inflammatory effects of hydroalcoholic extract and two biflavonoids from Garcinia gardneriana leaves in mouse paw oedema

Garcinia gardneriana (Planch. & Triana) Zappi (Clusiaceae) is widely distributed in Brazil and used in folk medicine to treat inflammation, pain, and urinary tract and other infections. However, very few studies have analyzed these therapeutic effects. In this study, the anti-inflammatory effects of the hydroalcoholic extracts from Garcinia gardneriana (HEGG) and some of its isolated biflavonoids were evaluated. The results showed that HEGG from the leaves, bark and seeds reduced carrageenan-induced mouse paw inflammation, in addition to diminishing the myeloperoxidase activity in the stimulated tissues. The reduction of neutrophil infiltration by treatment with the HEGG from leaves was confirmed by histology. The leaf extract also reduced the paw oedema evoked by bradykinin, histamine, prostaglandin E2 and 12-O-tetradecanoylphorbol acetate. However, it partially decreased substance P and compound 48/80-caused paw oedema, without any influence on the arachidonic acid-induced oedema. Both of the isolated compounds, fukugetin and GB-2a, prevented the carrageenan-induced paw oedema. In conclusion, this study showed important anti-inflammatory effects of HEGG through its interaction with different intracellular signaling pathways, without interfering with the formation of arachidonic acid (AA) metabolites. These characteristics, in addition to the wide distribution and culturing ease of the plant, confirm its popular use and highlight its promise in the development of new anti-inflammatory drugs.     

Central effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice

Ethnopharmacological relevance

Petiveria alliacea L. (tipi) a shrub from Phytolaccaceae family is popularly used in folk medicine for treating a wide variety of disorders in South and Central America.

Aim of the study

To investigate the neuropharmacological properties on experimental animals.

Materials and methods

The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in the classical behavioral models (open-field, elevated plus maze-EPM, rotarod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests) using mice. These fractions were administered intraperitoneally and orally to female mice at single doses of 100 and 200 mg/kg.

Results

All these fractions decreased the locomotor activity, rearing and grooming in the open-field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rotarod test. On EPM, all the fractions of tipi presented a significant reduction on the time of permanence in the open arms, indicating an absence of anxiolytic-like effect. In addition, the fractions increased the immobility time in the forced swimming test and potentiated pentobarbital-induced sleeping time in mice, confirmed a probable sedative and central depressant effect. Furthermore, the fractions increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant.

Conclusion

Our results suggest that the fractions of P. alliacea L. contains biologically active substance(s) that might be acting in the CNS and have significant depressant and anticonvulsant potentials, supporting folk medicine use of this plant.