A mathematical model for nutrient-limited uniaxial growth of a compressible tissue.

We consider the uniaxial growth of a tissue or colony of cells, where a nutrient (or some other chemical) required for cell proliferation is supplied at one end, and is consumed by the cells. An example would be the growth of a cylindrical yeast colony in the experiments described by Vulin et al. (2014). We develop a reaction-diffusion model of this scenario which couples nutrient concentration and cell density on a growing domain. A novel element of our model is that the tissue is assumed to be compressible. We define replicative regions, where cells have sufficient nutrient to proliferate, and quiescent regions, where the nutrient level is insufficient for this to occur. We also define pathlines, which allow us to track individual cell paths within the tissue. We begin our investigation of the model by considering an incompressible tissue where cell density is constant before exploring the solution space of the full compressible model. In a large part of the parameter space, the incompressible and compressible models give qualitatively similar results for both the nutrient concentration and cell pathlines, with the key distinction being the variation in density in the compressible case. In particular, the replicative region is located at the base of the tissue, where nutrient is supplied, and nutrient concentration decreases monotonically with distance from the nutrient source. However, for a highly-compressible tissue with small nutrient consumption rate, we observe a counter-intuitive scenario where the nutrient concentration is not necessarily monotonically decreasing, and there can be two replicative regions. For parameter values given in the paper by Vulin et al. (2014), the incompressible model slightly overestimates the colony length compared to experimental observations; this suggests the colony may be somewhat compressible. Both incompressible and compressible models predict that, for these parameter values, cell proliferation is ultimately confined to a small region close to the colony base.

Post-zygotic genomic changes in glutamate and dopamine pathway genes may explain discordance of monozygotic twins for schizophrenia.

BACKGROUND: Monozygotic twins are valuable in assessing the genetic vs environmental contribution to diseases. In the era of complete genome sequences, they allow identification of mutational mechanisms and specific genes and pathways that offer predisposition to the development of complex diseases including schizophrenia. METHODS: We sequenced the complete genomes of two pairs of monozygotic twins discordant for schizophrenia (MZD), including one representing a family tetrad. The family specific complete sequences have allowed identification of post zygotic mutations between MZD genomes. It allows identification of affected genes including relevant network and pathways that may account for the diseased state in pair specific patient. RESULTS: We found multiple twin specific sequence differences between co-twins that included small nucleotides [single nucleotide variants (SNV), small indels and block substitutions], copy number variations (CNVs) and structural variations. The genes affected by these changes belonged to a number of canonical pathways, the most prominent ones are implicated in schizophrenia and related disorders. Although these changes were found in both twins, they were more frequent in the affected twin in both pairs. Two specific pathway defects, glutamate receptor signaling and dopamine feedback in cAMP signaling pathways, were uniquely affected in the two patients representing two unrelated families. CONCLUSIONS: We have identified genome-wide post zygotic mutations in two MZD pairs affected with schizophrenia. It has allowed us to use the threshold model and propose the most likely cause of this disease in the two patients studied. The results support the proposition that each schizophrenia patient may be unique and heterogeneous somatic de novo events may contribute to schizophrenia threshold and discordance of the disease in monozygotic twins.

Systemic and regional hemodynamic effects of acute and prolonged treatment with urapidil or prazosin in normotensive and spontaneously hypertensive rats.

The regional and systemic hemodynamics of urapidil and prazosin were investigated after intravenous (1 mg/kg or 0.01 mg/kg, respectively) and prolonged (three weeks) oral treatment (20 mg/kg a day or 2 mg/kg a day, respectively) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Following intravenous administration, both urapidil and prazosin decreased mean arterial pressure, mediated through a decrease in total peripheral resistance and accompanied by a transient increase in heart rate in both strains. The changes in regional circulations were more widespread after urapidil, but of longer duration after prazosin. Prolonged administration of urapidil or prazosin resulted in a significant decrease in mean arterial pressure and total peripheral resistance only in SHR. With urapidil treatment, the decrease in vascular resistance was distributed throughout all circulations, with no change in heart rate or cardiac index. Heart rate increased in WKY rats and cardiac index increased in SHR following prazosin treatment. Cardiac mass remained unchanged following treatment with either drug.

Urapidil in normotensive and spontaneously hypertensive rats: the effects on systemic and regional haemodynamics and cardiac mass.

The effects of treatment for three weeks with urapidil (10 mg/kg p.o. twice daily) on systemic and regional haemodynamics and cardiac mass were studied in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Urapidil decreased mean arterial pressure and total peripheral resistance index (176 +/- 3 versus 145 +/- 5 mmHg and 0.61 +/- 0.02 versus 0.49 +/- 0.02 units, respectively; each P less than 0.01) in SHR without affecting heart rate, cardiac index or cardiac mass. No systemic haemodynamic changes were observed in WKY rats. All organ vascular resistances decreased significantly in SHR and blood flow increased to skin (P less than 0.01) and kidneys (P less than 0.05). These data indicate that urapidil is a potent antihypertensive agent in SHR which reduced mean arterial pressure through a decreased total peripheral resistance that was distributed throughout all circulations. Despite these haemodynamic changes, cardiac mass did not change.

[Meningitis due to Enterococcus faecalis]. / Meningitis a Enterococcus faecalis.

Enterococcus faecalis meningitis is an infrequent entity that accounts for less than 1% of all suppurative meningitis in the adult. Usually, this infection affects patients with compromised host defenses or those who have congenital or acquired CNS lesions mainly as intrahospitalary infections. An 85 year old woman from our community (Tandil county) without any predisposed condition, was admitted in the hospital in an unconscious state (grade 3 Glasgow's index), meningeal signs and purulent CSF, from which E. faecalis was isolated. The patient was treated with IV Ampicillin and Gentamycin (17 days), intrathecal Gentamycin (4 days) and IV dexametasona (6 days). The clinical and bacteriological remission was achieved, without any sequel or relapse during 2 years follow up.

Hemodynamic effects of prolonged treatment with diltiazem in conscious normotensive and spontaneously hypertensive rats.

To determine systemic and regional hemodynamic effects of prolonged treatment with the calcium antagonist diltiazem (30 mg/kg twice daily by gastric gavage, for 3 weeks), data from 12 Wistar-Kyoto (WKY) and 10 spontaneously hypertensive (SHR) rats were compared with those obtained from 11 WKY and 10 SHR controls treated with the vehicle. Systemic and regional hemodynamics were determined in the conscious, unrestrained state using the reference sample microsphere method. Mean arterial pressure (MAP) decreased in SHR by 9% (183 +/- 4 to 167 +/- 4 mm Hg; p less than 0.05) but remained unchanged in WKY, while cardiac index (CI) tended to decrease in both strains; heart rate fell by 15% only in WKY (481 +/- 10 to 354 +/- 13 beats/min; p less than 0.05). Total peripheral resistance index (TPRI) tended to decrease in SHR but to increase in WKY. Organ blood flow in SHR decreased in skin and splanchnic organs, while organ vascular resistance decreased in brain and increased in splanchnic organs. In contrast, organ blood flow increased in heart and decreased in kidneys and skin of the WKY, while organ vascular resistance decreased in heart and increased in kidneys and skin. Thus, diltiazem produced nonuniform and different hemodynamic effects in the two strains. Further, diltiazem did not alter the cardiac mass in either rat strain. We therefore conclude that diltiazem demonstrated a mild hypotensive effect in SHR that was associated with slight reductions in CI and TPRI, the latter being nonuniformly distributed in the component organ circulations.

The MEX.156 sex-limited lethal x chromosome of Drosophila melanogaster: moment of action

O presente trabalho teve por objetivo estimar o momento de açäo do letal Mex.156, limitado ao sexo feminino, do cromossomo X de Drosophila melanogaster

Meningitis a Enterococcus faecalis / [Meningitis due to Enterococcus faecalis]

Enterococcus faecalis meningitis is an infrequent entity that accounts for less than 1

of all suppurative meningitis in the adult. Usually, this infection affects patients with compromised host defenses or those who have congenital or acquired CNS lesions mainly as intrahospitalary infections. An 85 year old woman from our community (Tandil county) without any predisposed condition, was admitted in the hospital in an unconscious state (grade 3 Glasgow’s index), meningeal signs and purulent CSF, from which E. faecalis was isolated. The patient was treated with IV Ampicillin and Gentamycin (17 days), intrathecal Gentamycin (4 days) and IV dexametasona (6 days). The clinical and bacteriological remission was achieved, without any sequel or relapse during 2 years follow up.