Novel Approach to Simulate Sleep Apnea Patients for Evaluating Positive Pressure Therapy Devices

Bench testing is a useful method to characterize the response of different automatic positive airway pressure (APAP) devices under well-controlled conditions. However, previous models did not consider the diversity of obstructive sleep apnea (OSA) patients’ characteristics and phenotypes. The objective of this proof-of-concept study was to design a new bench test for realistically simulating an OSA patient’s night, and to implement a one-night example of a typical female phenotype for comparing responses to several currently-available APAP devices. We developed a novel approach aimed at replicating a typical night of sleep which includes different disturbed breathing events, disease severities, sleep/wake phases, body postures and respiratory artefacts. The simulated female OSA patient example that we implemented included periods of wake, light sleep and deep sleep with positional changes and was connected to ten different APAP devices. Flow and pressure readings were recorded; each device was tested twice. The new approach for simulating female OSA patients effectively combined a wide variety of disturbed breathing patterns to mimic the response of a predefined patient type. There were marked differences in response between devices; only three were able to overcome flow limitation to normalize breathing, and only five devices were associated with a residual apnea-hypopnea index of <5/h. In conclusion, bench tests can be designed to simulate specific patient characteristics, and typical stages of sleep, body position, and wake. Each APAP device behaved differently when exposed to this controlled model of a female OSA patient, and should lead to further understanding of OSA treatment.     

Optional tool use: The case of wild bearded capuchins (Sapajus libidinosus) cracking cashew nuts by biting or by using percussors

Tool use in humans can be optional, that is, the same person can use different tools or no tool to achieve a given goal. Strategies to reach the same goal may differ across individuals and cultures and at the intra‐individual level. This is the first experimental study at the intra‐individual level on the optional use of a tool in wild nonhuman primates. We investigated optional tool use by wild bearded capuchins (Sapajus libidinosus) of Fazenda Boa Vista (FBV; Piauí, Brazil). These monkeys habitually succeed in cracking open the mesocarp of dry cashew nuts (Anacardium spp.) by pounding them with stones and/or by biting. We assessed whether availability of a stone and resistance of the nut affected capuchins' choice to pound or to bite the nuts and their rates of success. Sixteen capuchins (1–16 years) received small and large dry cashew nuts by an anvil together with a stone (Stone condition) or without a stone (No‐Stone condition). In the Stone conditions, subjects used it to crack the nut in 89.1% (large nuts) and 90.1% (small nut) of the trials. Nut size significantly affected the number of strikes used to open it. Availability of the stone significantly increased the average percent of success. In the No‐Stone conditions, monkeys searched for and used other percussors to crack the nuts in 54% of trials. In all conditions, age affects percentage of success and number of strikes to reach success. We argue that exclusive use of stones in other sites may be due to the higher abundance of stones at these sites compared with FBV. Since capuchins opened cashews with a tool 1–2 years earlier than they succeed at cracking more resistant palm nuts, we suggest that success at opening cashew nuts with percussors may support the monkeys' persistent efforts to crack palm nuts.     

Common antigen of oval and biliary epithelial cells (A6) is a differentiation marker of epithelial and erythroid cell lineages in early development of the mouse

Abstract. The A6 antigen - a surface-exposed component shared by mouse oval and biliary epithelial cells - was examined during prenatal development of mouse in order to elucidate its relation to liver progenitor cells. Immunohistochemical demonstration of the antigen was performed at the light and electron microscopy level beginning from the 9.5 day of gestation (26–28 somite pairs).
Up to the 11.5 day of gestation A6 antigen is found only in the visceral endoderm of yolk sac and gut epithelium, while liver diverticulum and liver are A6-negative. In the liver epithelial lineages A6 antigen behaves as a strong and reliable marker of biliary epithelial cells where it is found beginning from their emergence on the 15th day of gestation. It was not revealed in immature hepato-cytes beginning from the 16th day of gestation. However weak expression of the antigen was observed in hepato-blasts on 12–15 days of gestation possibly reflecting their ability to differentiate along either hepatocyte or biliary epithelial cell lineages.
Surprisingly, A6 antigen turned out to be a peculiar marker of the crythroid lineage: in mouse fetuses it distinguished A6 positive liver and spleen erythroblasts from A6 negative early hemopoietic cells of yolk sac origin. Moreover in the liver, A6 antigen probably distinguishes two waves of erythropoiesis: it is found on the erythroblasts from the 11.5 day of gestation onward while first extravascular erythroblasts appear in the liver on the 10th day of gestation. Both fetal and adult erythrocytes are A6-negative.
In the process of organogenesis A6 antigen was revealed in various mouse fetal organs. Usually it was found on plasma membranes of mucosal or ductular epithelial cells. Investigation of A6 antigen's physiological function would probably explain such specific localization.     

Accumulation of Pb and Zn in Gametophytes and Sporophytes of the Moss Funaria hygrometrica(Funariales)

Accumulation of lead and zinc was studied in the moss Funariahygrometrica Hedw. collected from mine tailings. Heavy metalaccumulation in gametophytes and sporophytes was quantifiedby graphite furnace atomic absorption spectrometry (GFAAS) andinductively coupled plasma-atomic emission spectrometry (ICP-AES).Pb and Zn accumulation in the placental zone was analysed byx-ray scanning electron microscopy (SEM) and transmission electronmicroscopy (TEM) microanalysis. Spectrometry showed that whilemoss gametophytes accumulated considerable concentrations ofheavy metals, sporophytes accumulated only small concentrationsof metals. X-ray SEM and TEM showed that the two metals accumulatedin placental transfer cells on both the gametophytic and sporophyticsides. To investigate the uptake pattern for both metals undercontrolled conditions, F. hygrometrica plants collected froma non-polluted site were treated in the laboratory with separatesolutions of Pb and Zn at two concentrations (10^-2and 10^-4 M)for 24 or 168 h. Metal accumulation was analysed separatelyin gametophytes and sporophytes using GFAAS and ICP–AES.Each generation had a different accumulation quotient for bothmetals, and gametophytes accumulated significantly more metalthan sporophytes. Concentrations of Zn in sporophytes were alwayshigher than concentrations of Pb. The findings are discussedin relation to the role performed by the gametophyte and theplacenta in the accumulation and sequestration of Pb and Zn.Copyright 2001 Annals of Botany Company Atomic spectroscopy, Funaria hygrometrica, gametophyte, Pb and Zn accumulation, sporophyte, x-ray TEM and SEM microanalysis     

Common antigens of mouse oval and biliary epithelial cells. Expression on newly formed hepatocytes

Two antigens - A6 and G7 - shared by mouse biliary epithelial and oval cells were revealed by monoclonal antibodies raised in rat immunized with oval-cell-enriched liver fraction. Oval cells were induced in CBA or F1 (CBA x C57BL6) mice by a combination of a single injection of the alkylating drug Dipin with partial hepatectomy. In normal liver A6 antigen was localized, using light and electron microscopy, in biliary epithelial cells of all ducts including Hering canals. Some bile ductal and Hering cells were A6-negative. Occasionally, A6 antigen was present in single hepatocytes forming the periportal ends of hepatic cords. In preneoplastic and tumorous liver A6 antigen was present in bile ductal and oval cells and in a fraction of newly formed hepatocytes and tumor cells. G7 antigen was revealed in normal, precancerous and tumorous liver in biliary epithelial and oval cells but not in hepatocytes. A6 and G7 antigens were not liver-specific: they were expressed in various normal organs and tissues, especially in epithelia. In studies of mouse liver lineages A6 antigen can be used as a common marker of biliary epithelial and oval cells and hepatocytes at certain stages of differentiation. G7 antigen is a marker of oval and biliary epithelial cells. There was a striking similarity in A6 antigen localization to that of human blood group antigens in normal liver and liver tumors. A6 antigen may thus provide a useful tool for the study of neoexpression of human blood group antigens in liver tumors.     

Tissue specific regulation of "peripheral-type" benzodiazepine receptor density after chemical sympathectomy

The characteristics of [3H]Ro 5-4864 binding to "peripheral" benzodiazepine receptors (PBR) in the central nervous system and peripheral tissues were examined after chemical sympathectomy with 6-hydroxydopamine (6-OHDA). One week after the intracisternal administration of 6-OHDA, the number of [3H]Ro 5-4864 binding sites (Bmax) in the hypothalamus and striatum increased 41 and 50%, respectively, concurrent with significant reductions in catecholamine content. An increase (34%) in the Bmax of [3H]Ro 5-4864 to cardiac ventricle was observed one week after parenteral 6-OHDA administration. In contrast, the Bmax of [3H]Ro 5-4864 to pineal gland decreased 48% after 6-OHDA induced reduction in norepinephrine content. The Bmax values for [3H]Ro 5-4864 binding to other tissues (including lung, kidney, spleen, cerebral cortex, cerebellum, hippocampus and olfactory bulbs) were unaffected by 6-OHDA administration. The density of pineal, but not cardiac PBR was also reduced after reserpine treatment, an effect reversed by isoproterenol administration. These findings demonstrate that alterations in sympathetic input may regulate the density of PBR in both the central nervous system and periphery in a tissue specific fashion.     

Subcellular Localization of "Peripheral-Type" Binding Sites for Benzodiazepines in Rat Brain

The binding of [3H]Ro 5-4864, a specific ligand for "peripheral-type" benzodiazepine binding sites and [3H]Ro 15-1788, a specific ligand for the central benzodiazepine receptors, was determined in subcellular fractions of rat brain. As previously reported, the highest levels of "peripheral-type" benzodiazepine binding sites and benzodiazepine receptors were found in the crude P1 and P2 fractions, respectively. Purification of these crude fractions revealed that high levels of both [3H]Ro 5-4864 and [3H]Ro 15-1788 binding were present in the mitochondrial and synaptosomal fractions. In contrast, the purified nuclei and myelin contained low levels of both [3H]Ro 5-4864 and [3H]Ro 15-1788 binding.     

Determination of Endogenous Indole-3-Acetic Acid in Plagiochila arctica (Hepaticae)

Endogenous indole-3-acetic acid (IAA) was found in axenically cultured gametophytes of the leafy liverwort, Plagiochila arctica Bryhn and Kaal., by high-performance liquid chromatography with electrochemical detection. Identification of the methylated auxin was confirmed by gas chromatography-mass spectrometry. Addition of 57 micromolar IAA to cultures increased relative production of ethylene. This is the first definitive (gas chromatography-mass spectrometry) demonstration of the natural occurrence of IAA in a bryophyte.     

Observations sur la spécificité de la coloration aux acides phosphotungstique et phosphomolybdique

Résumé Les Auteurs ont démontré que, en conditions histochimiques sur du matériel fixé au formol, les acides phosphotungstique et phosphomolybdique ont une double action: 1. une action oxydative à la charge des radicaux PAS-positifs (vic-glycols et éthyleniques) en milieu aqueux, et à la charge des radicaux aminiques en milieu anhydre; cette action entraine la transformation de ces radicaux en aldéhydes; 2. la formation d'une liaison chimique entre les aldéhydes et les molécules des acides phosphomolybdique et phosphotungstique. — La coloration du collagène, au contraire, n'est pas due ni aux radicaux aminiques ni vic-glycols et implique un mécanisme encore inconnu.

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Observations about the specificity of staining of phosphotungstic and phosphomolybdic acid

Summary The authors demonstrated that phosphotungstic and phosphomolybdic acid applied to formol-fixed tissues explete two following actions: 1. An oxidative action on the PAS-positive radicals (double bonds, vic-glycols groups) if in water solution and on aminogroups if in anhydrous solution. This oxidation results in a production of aldehydic radicals 2. The formation of chemical bonds between the aldehydic new-formed groups and the molecules of phosphotungstic or phosphomolybdicacid.— However, the above mentioned mechanism of action is not applicable to the collagen staining for which a different explanation has to be supposed.