Systematized water content calculation in cartilage using T1-mapping MR estimations: design and validation of a mathematical model.

BACKGROUND: Up to 80 % of cartilage is water; the rest is collagen fibers and proteoglycans. Magnetic resonance (MR) T1-weighted measurements can be employed to calculate the water content of a tissue using T1 mapping. In this study, a method that translates T1 values into water content data was tested statistically. MATERIALS AND METHODS: To develop a predictive equation, T1 values were obtained for tissue-mimicking gelatin samples. 1.5 T MRI was performed using inverse angle phase and an inverse sequence at 37 (±0.5) °C. Regions of interest were manually delineated and the mean T1 value was estimated in arbitrary units. Data were collected and modeled using linear regression. To validate the method, articular cartilage from six healthy pigs was used. The experiment was conducted in accordance with the Danish Animal Experiment Committee. Double measurements were performed for each animal. Ex vivo, all water in the tissue was extracted by lyophilization, thus allowing the volume of water to be measured. This was then compared with the predicted water content via Lin's concordance correlation coefficient at the 95 % confidence level. RESULTS: The mathematical model was highly significant when compared to a null model (p < 0.0001). 97.3 % of the variation in water content can be explained by absolute T1 values. Percentage water content could be predicted as 0.476 + (T1 value) × 0.000193 × 100 %. We found that there was 98 % concordance between the actual and predicted water contents. CONCLUSION: The results of this study demonstrate that MR data can be used to predict percentage water contents of cartilage samples. LEVEL OF EVIDENCE: 3 (case-control study).

Concomitant changes in cross-sectional area and water content in skeletal muscle after resistance exercise.

This study investigated how one bout (1EX) and three bouts (3EX) of strenuous resistance exercise affected the cross-sectional area (CSA) and water content (WC) of the quadriceps muscle and patella tendon (PT), 4 h and 52 h after the last exercise bout. Ten healthy untrained male subjects performed 1EX with one leg and 3EX with the other leg. CSA and WC were measured with magnetic resonance imaging 10, 20 and 30 cm proximal to the tibia plateau (TP) for the muscle, and at the proximal, central and distal site for the PT prior to exercise, and 4 h and 52 h after the last exercise bout. Ten centimeter above the TP, muscle CSA was significantly increased at 4 h (1EX: 13 ± 5%; 3EX: 13 ± 4%) and 52 h (1EX: 16 ± 5%; 3EX: 16 ± 5%) compared with baseline. Muscle WC was significantly increased at 4 h (1EX: 7 ± 1%; 3EX: 6 ± 2%) and 52 h (1EX: 8 ± 2%; 3EX: 8 ± 3%) compared to baseline. PT central CSA was significantly reduced at 52 h (3EX: 14 ± 2%) compared with baseline and (3EX: 13 ± 1%) compared with 4 h. Present data demonstrate that strenuous resistance exercise results in an acute increase in muscle WC and underlines the importance of ensuring sufficient time between the last exercise bout and the determination of anatomical dimensions in muscles.

Ventriculoperitoneal shunt as a primary neurosurgical procedure in newborn posthemorrhagic hydrocephalus: report of a series of 47 shunted patients.

PURPOSE: Intraventricular hemorrhage is the most common cause of infantile acquired hydrocephalus. Our objective is to determine if the implantation of ventriculoperitoneal shunt in posthemorrhagic hydrocephalus as a primary and definitive neurosurgical treatment, with no previous temporary procedures, would decrease complication rates with good functional outcomes. METHODS: Two hundred seventy-one patients with germinal matrix hemorrhage were diagnosed at the Carlos Haya Hospital between 2003 and 2010. Forty-seven patients underwent ventriculoperitoneal shunt after developing symptomatic hydrocephalus. The minimum weight required for shunt implantation was 1,500 g. We recorded complications related to the surgical procedure and analyzed functional state with a self-developed four-grade scale. RESULTS: One hundred thirty-nine (51.3 %) patients with intraventricular hemorrhage developed ventricular dilatation, but only 47 patients (17.34 %) needed shunting. In seven cases, temporary neurosurgical procedures were performed, but in all of them, this was followed by ventriculoperitoneal shunt implantation. The infection rate was 4.25 %, and shunt obstruction rate was 4.25 %. More than 80 % of patients were classified as good or excellent functional state. Mean follow-up period was 38.75 months (SD, 27.09; range, 1-102 months). CONCLUSIONS: Ventriculoperitoneal shunting as a primary neurosurgical treatment in posthemorrhagic hydrocephalus would decrease surgical morbidity with good functional outcome.

Water-content calculation in growth plate and cartilage using MR T1-mapping design and validation of a new method in a porcine model.

OBJECTIVE: There is a close relation between cartilage health and its hydration state. Current magnetic resonance methods allow visualizing this tissue. However, a quantitative analysis is more useful when studying disease. The purpose of this study was to quantify water content in cartilage using magnetic resonance without contrast agents. MATERIALS AND METHODS: Water-content estimations using T1 magnetic resonance mapping were done first in eight gelatin samples where the water content was previously known. The same method was used in the physeal areas of eight skeletally immature 30-kg pigs. To calculate accuracy, T1 calculations were compared to dry-freeze, which is considered the gold standard because it can remove the total water content form a tissue. Four fresh cartilage and seven gelatin samples were dry-frozen. Water content obtained from dry-freeze was compared to the one calculated from T1 map values. A mathematical model and statistical analysis were used to calculate the predictive value of the method and its significance. RESULTS: T1-map-based magnetic resonance method can calculate water content in cartilage with an accuracy of 97.3 %. We calculated a coefficient of variance for this method against dry-frozen sample of 3.68 (SD = 1.2) in gelatin samples, and 2.73 (SD = 1.3) in in vivo samples. Between two independent observers, the coefficient of variance was 0.053, which suggests it can be easily reproduced. CONCLUSIONS: Magnetic resonance was able to calculate, with high accuracy, the cartilage water content using T1 mapping sequences.

Tomatidine promotes the inhibition of 24-alkylated sterol biosynthesis and mitochondrial dysfunction in Leishmania amazonensis promastigotes.

Leishmaniasis is a set of clinically distinct infectious diseases caused by Leishmania, a genus of flagellated protozoan parasites, that affects ~12 million people worldwide, with ~2 million new infections annually. Plants are known to produce substances to defend themselves against pathogens and predators. In the genus Lycopersicon, which includes the tomato, L. esculentum, the main antimicrobial compound is the steroidal glycoalkaloid α-tomatine. The loss of the saccharide side-chain of tomatine yields the aglycone tomatidine. In the present study, we investigated the effects of tomatidine on the growth, mitochondrial membrane potential, sterol metabolism, and ultrastructure of Leishmania amazonensis promastigotes. Tomatidine (0·1 to 5 µM) inhibited parasite growth in a dose-dependent manner (IC(50)=124±59 nM). Transmission electron microscopy revealed lesions in the mitochondrial ultrastructure and the presence of large vacuoles and lipid storage bodies in the cytoplasm. These structural changes in the mitochondria were accompanied by an effective loss of mitochondrial membrane potential and a decrease in ATP levels. An analysis of the neutral lipid content revealed a large depletion of endogenous 24-alkylated sterols such as 24-methylene-cholesta-5, 7-dien-3ß-ol (5-dehydroepisterol), with a concomitant accumulation of cholesta-8, 24-dien-3ß-ol (zymosterol), which implied a perturbation in the cellular lipid content. These results are consistent with an inhibition of 24-sterol methyltransferase, an important enzyme responsible for the methylation of sterols at the 24 position, which is an essential step in the production of ergosterol and other 24-methyl sterols.

geno5mC: A Database to Explore the Association between Genetic Variation (SNPs) and CpG Methylation in the Human Genome.

Genetic variation, gene expression and DNA methylation influence each other in a complex way. To study the impact of sequence variation and DNA methylation on gene expression, we generated geno5mC, a database that contains statistically significant SNP-CpG associations that are biologically classified either through co-localization with known regulatory regions (promoters and enhancers), or through known correlations with the expression levels of nearby genes. The SNP rs727563 can be used to illustrate the usefulness of this approach. This SNP has been associated with inflammatory bowel disease through GWAS, but it is not located near any gene related to this phenotype. However, geno5mC reveals that rs727563 is associated with the methylation state of several CpGs located in promoter regions of genes reported to be involved in inflammatory processes. This case exemplifies how geno5mC can be used to infer relevant and previously unknown interactions between described disease-associated SNPs and their functional targets.

Multi-scale analysis of radio-frequency performance of 2D-material based field-effect transistors.

Two-dimensional materials (2DMs) are a promising alternative to complement and upgrade high-frequency electronics. However, in order to boost their adoption, the availability of numerical tools and physically-based models able to support the experimental activities and to provide them with useful guidelines becomes essential. In this context, we propose a theoretical approach that combines numerical simulations and small-signal modeling to analyze 2DM-based FETs for radio-frequency applications. This multi-scale scheme takes into account non-idealities, such as interface traps, carrier velocity saturation, or short channel effects, by means of self-consistent physics-based numerical calculations that later feed the circuit level via a small-signal model based on the dynamic intrinsic capacitances of the device. At the circuit stage, the possibilities range from the evaluation of the performance of a single device to the design of complex circuits combining multiple transistors. In this work, we validate our scheme against experimental results and exemplify its use and capability assessing the impact of the channel scaling on the performance of MoS2-based FETs targeting RF applications.

[Neuronal ceroid lipofuscinosis. Type 6 late infantile variant in two compound heterozygous siblings with novel mutations]. / Lipofuscinosis ceroidea neuronal. Variante infantil tardía de tipo 6 en dos hermanos heterocigotos compuestos con mutaciones nuevas.

INTRODUCTION: There are 14 forms of lipofuscinosis, among them type 6 in its late childhood form is found, it starts between three and eight years with epilepsy, motor disorders, myoclonus, dysarthria, ataxia and neurological regression associated with vision loss and motor skills, and early death. It occurs from mutations in the CLN6 gene, most patients have homozygote variants associated with consanguinity, and rarely, with compound heterozygote variants. CASE REPORT: Siblings, started at 4 and 5 years each, with unstable gear, frequent falls and difficult running. Subsequently, loss of gait, myoclonus, dysphagia, and hallucinations. On physical examination, present optic nerve atrophy, Babinski and trunk ataxia. Electroencephalogram with widespread slow wave bursts during non-REM sleep, non photoparoxystic response, MRI with periventricular white substance hyperintensity, cerebellar atrophy and cortical. Panel of lipofuscinosis report two mutations, c.552del and c.244G>C, not described previously, in both patients. The mother was the carrier of the 552 deletion and the father and paternal grandmother of the G>C substitution (Gly82Arg). CONCLUSIONS: Differential diagnosis in neuroregression disorders is difficult because clinical signs are nonspecific, like many other neurodegenerative disorders with progressive myoclonic epilepsy. We report the clinical findings in two Mexican siblings with the late childhood variant of CLN6 with two new heterozygote mutations that contribute to the knowledge of mutations in the Mexican population and point out the relevance of performing next-generation genetic sequencing studies which will allow a better genetic counseling practice.

TITLE: Lipofuscinosis ceroidea neuronal. Variante infantil tardía de tipo 6 en dos hermanos heterocigotos compuestos con mutaciones nuevas.Introducción. Existen 14 formas de lipofuscinosis. La de tipo 6, en su forma infantil tardía, comienza entre los 3 y 8 años con alteraciones motoras, mioclonos, disartria, ataxia, pérdida de la visión y las habilidades motoras, y muerte temprana. Ocurre por mutaciones en el gen CLN6. La mayoría de los pacientes presenta variantes en estado homocigoto, asociadas a consanguinidad o endogamia, y son poco frecuentes las variantes en estado heterocigoto compuesto. Casos clínicos. Hermanos con síntomas desde los 4 y 5 años, con marcha inestable, caídas frecuentes, posteriormente pérdida de la marcha, mioclonías, disfagia y alucinaciones visuales. En el examen físico presentaban atrofia del nervio óptico, Babinski y ataxia del tronco. El electroencefalograma mostraba brotes de ondas lentas generalizadas, sin respuesta fotoparoxística, y la resonancia magnética de cráneo, hiperintensidad de la sustancia blanca periventricular, y atrofia cerebelosa y cortical. El panel de lipofuscinosis reveló dos mutaciones nuevas en el gen CLN6, c.552del y c.244G>C (p.Gly82Arg), no descritas previamente. La madre resultó portadora de la deleción 552, y el padre y la abuela paterna, de la sustitución G>C (Gly82Arg). Conclusiones. El diagnóstico diferencial en los trastornos con neurorregresión se dificulta debido a que los signos clínicos son inespecíficos, similares a otras epilepsias mioclónicas progresivas. Presentamos los hallazgos clínicos en dos hermanos mexicanos con la variante infantil tardía de CLN6 por dos mutaciones heterocigotas nuevas que contribuyen al conocimiento de las mutaciones en la población mexicana y señalan la relevancia de realizar estudios genéticos aplicando la secuenciación de nueva generación para permitir un adecuado asesoramiento genético.

Assessment of three electrolyte-molecule electrostatic interaction models for 2D material based BioFETs.

BioFETs based on two-dimensional materials (2DMs) offer a unique opportunity to enhance, at a low cost, the sensitivity of current biosensors enabling the design of compact devices compatible with standard CMOS technology. The unique combination of large exposed surface areas and minimal thicknesses of 2DMs is an outstanding feature for these devices, and the assessment of their behaviour requires combined experimental and theoretical efforts. In this work we present a 2D-material based BioFET simulator including complex electrolyte reactions and analysing different models for the electrolyte-molecule interaction. These models describe how the molecular charge is screened by the electrolyte ions when their distributions are modified. The electrolyte simulation is validated against experimental results as well as against the analytical predictions of the Debye-Hückel approximation. The role of the electrolyte charge screening as well as the impact of the interaction model on the device responsivity are analysed in detail. The results are discussed in order to conclude about the consequences of employing different interaction approximations for the simulation of BioFETs and more generally on the correct modelling of biomolecule-device interaction in BioFETs.

The role of connexin43-Src interaction in astrocytomas: A molecular puzzle.

Connexin43 (Cx43) as a building block of gap junction channels and hemichannels exerts important functions in astrocytes. When these cells acquire a malignant phenotype Cx43 protein but not mRNA levels are downregulated, being negligible in high-grade astrocytoma or glioblastoma multiforme, the most common and deadliest of malignant primary brain tumors in adults. Some microRNAs associated to glioma target Cx43 and could explain the lack of correlation between mRNA and protein levels of Cx43 found in some high-grade astrocytomas. More importantly, these microRNAs could be a promising therapeutic target. A great number of studies have confirmed the relationship between cancer and connexins that was proposed by Loewenstein more than 40years ago, but these studies have also revealed that this is a very complex relationship. Indeed, restoring Cx43 to glioma cells reduces their rate of proliferation and their tumorigenicity but this tumor suppressor effect could be counterbalanced by its effects on invasiveness, adhesion and migration. The mechanisms underlying these effects suggest the participation of a great variety of proteins that bind to different regions of Cx43. The present review focuses on an intrinsically disordered region of the C-terminal domain of Cx43 in which converges the interaction of several proteins, including the proto-oncogene Src. We summarize data that indicate that Cx43-Src interaction inhibits the oncogenic activity of Src and promotes a conformational change in the structure of Cx43 that allosterically modifies the binding to other important signaling proteins. As a consequence, crucial cell functions, such as proliferation or migration, could be strongly affected. We propose that the knowledge of the structural basis of the antitumorigenic effect of Cx43 on astrocytomas could help to design new therapies against this incurable disease.

Lipofuscinosis ceroidea neuronal. Variante infantil tardía de tipo 6 en dos hermanos heterocigotos compuestos con mutaciones nuevas / Neuronal ceroid lipofuscinosis. Type 6 late infantile variant in two compound heterozygous siblings with novel mutations

Introducción: Existen 14 formas de lipofuscinosis. La de tipo 6, en su forma infantil tardía, comienza entre los 3 y 8 años con alteraciones motoras, mioclonos, disartria, ataxia, pérdida de la visión y las habilidades motoras, y muerte temprana. Ocurre por mutaciones en el gen CLN6. La mayoría de los pacientes presenta variantes en estado homocigoto, asociadas a consanguinidad o endogamia, y son poco frecuentes las variantes en estado heterocigoto compuesto. Casos clínicos: Hermanos con síntomas desde los 4 y 5 años, con marcha inestable, caídas frecuentes, posteriormente pérdida de la marcha, mioclonías, disfagia y alucinaciones visuales. En el examen físico presentaban atrofia del nervio óptico, Babinski y ataxia del tronco. El electroencefalograma mostraba brotes de ondas lentas generalizadas, sin respuesta fotoparoxística, y la resonancia magnética de cráneo, hiperintensidad de la sustancia blanca periventricular, y atrofia cerebelosa y cortical. El panel de lipofuscinosis reveló dos mutaciones nuevas en el gen CLN6, c.552del y c.244G>C (p.Gly82Arg), no descritas previamente. La madre resultó portadora de la deleción 552, y el padre y la abuela paterna, de la sustitución G>C (Gly82Arg). Conclusiones: El diagnóstico diferencial en los trastornos con neurorregresión se dificulta debido a que los signos clínicos son inespecíficos, similares a otras epilepsias mioclónicas progresivas. Presentamos los hallazgos clínicos en dos hermanos mexicanos con la variante infantil tardía de CLN6 por dos mutaciones heterocigotas nuevas que contribuyen al conocimiento de las mutaciones en la población mexicana y señalan la relevancia de realizar estudios genéticos aplicando la secuenciación de nueva generación para permitir un adecuado asesoramiento.(AU)

Introduction: There are 14 forms of lipofuscinosis, among them type 6 in its late childhood form is found, it starts between three and eight years with epilepsy, motor disorders, myoclonus, dysarthria, ataxia and neurological regression associated with vision loss and motor skills, and early death. It occurs from mutations in the CLN6 gene, most patients have homozygote variants associated with consanguinity, and rarely, with compound heterozygote variants. Case report: Siblings, started at 4 and 5 years each, with unstable gear, frequent falls and difficult running. Subsequently, loss of gait, myoclonus, dysphagia, and hallucinations. On physical examination, present optic nerve atrophy, Babinski and trunk ataxia. Electroencephalogram with widespread slow wave bursts during non-REM sleep, non photoparoxystic response, MRI with periventricular white substance hyperintensity, cerebellar atrophy and cortical. Panel of lipofuscinosis report two mutations, c.552del and c.244G>C, not described previously, in both patients. The mother was the carrier of the 552 deletion and the father and paternal grandmother of the G>C substitution (Gly82Arg). Conclusions: Differential diagnosis in neuroregression disorders is difficult because clinical signs are nonspecific, like many other neurodegenerative disorders with progressive myoclonic epilepsy. We report the clinical findings in two Mexican siblings with the late childhood variant of CLN6 with two new heterozygote mutations that contribute to the knowledge of mutations in the Mexican population and point out the relevance of performing next-generation genetic sequencing studies which will allow a better genetic counseling practice.(AU)

Regulation of glycogenolysis in the liver of the newborn rat in vivo. Inhibitory effect of glucose.

Newborn rats were injected immediately after delivery with glucose or glucose plus mannoheptulose, and the time-courses of liver glycogen, plasma glucose insulin and glucagon concentration were studied. The administration of glucose prevented both liver glycogenolysis and the increase in plasma glucagon concentration, which normally occurs immediately after delivery. In addition, the administration of glucose prevented the decrease of plasma glucose and insulin concentration which normally occurs during the first hour of extrauterine life. Supplementation of glucose with mannoheptulose prevented the increase of plasma insulin concentrations caused by the administration of glucose; liver glycogenolysis, however, was not stimulated in these circumstances. The increase in the rate of glycogenolysis caused by the administration of glucagon was prevented in newborn rats previously treated with glucose. These results suggest that glucose exerts an inhibitory effect on the stimulation of neonatal liver glycogenolysis by glucagon.

The role of ATP/ADP ratio in the control of hepatic gluconeogenesis during the early neonatal period.

The hepatic ATP/ADP ratio showed significant changes during the first day of postnatal life in starved newborn rats. The occurrence of a positive linear correlation between the ATP/ADP ratio and the gluconeogenic capacity in vivo is reported in the newborn rat during the first day of life.

Changes in adult rat liver mitochondrial populations at different energy states analyzed by flow cytometry.

The present work studies the changes in green fluorescence intensity after Rh-123 staining of the low (LFP) and the high fluorescence populations (HFP) in isolated mitochondria from rat liver. The results show that the HFP represents a mitochondrial compartment less sensitive to changes in energy states. In addition, it is concluded that the use of Rh-123 to monitor changes in mitochondrial membrane potential should be undertaken with caution because, under certain circumstances, there is no correlation between the Rh-123 intensity of fluorescence due to its uptake by mitochondria and previously reported changes in the mitochondrial membrane potential.

Effect of streptozotocin-induced diabetes on sex differences in biliary lipid secretion in the rat.

Diabetes mellitus is often associated with lipid abnormalities that may differ with sex. In this work we studied biliary lipid secretion in male and female anaesthetized Wistar rats (250 g). Diabetes was induced by a single intraperitoneal injection of streptozotocin (6 mg/100 body weight) 6 days before carrying out the studies on bile secretion. Our results confirm the existence of sex differences in bile formation and composition, most of them probably due to a higher (+27%) bile acid output in the female animals. Diabetes induced profound alterations in these sex differences. (a) Bile flow was reduced in both sexes, but more markedly so in female diabetic rats; thus the difference observed in healthy animals was reduced (from 2.22 to 1.58 and from 1.84 to 1.40 microliters/min per g liver in female and male rats, respectively). (b) Bile acid and phosphatidylcholine outputs were increased to a similar extent (bile acid output: from 46.7 to 55.8 nmol/min per g liver, in females and from 36.8 to 50.7 nmol/min per g liver, in males; phosphatidylcholine output: from 3.3 to 13.1 nmol/min per g liver, in females and from 4.5 to 12.5 nmol/min per g liver, in males), and hence the sex differences were abolished. (c) Cholesterol output was increased in both sexes, but this enhancement was significantly higher in female rats (from 0.75 to 1.31 and from 0.65 to 0.89 nmol/min per g liver, in females and males, respectively). (d) The fractional pool of phospholipid species secreted into bile was different in female compared with male rats. The percentage of phosphatidylcholine was higher in female than in male healthy rats. Streptozotocin treatment reversed this proportion, which suggests that changes in the phospholipid composition of the canalicular plasma membrane may play a role in the observed alterations in biliary lipid secretion during diabetes mellitus. Most of the above-described streptozotocin-induced changes were prevented by insulin replacement from the 3rd to the 6th days after streptozotocin injection. In summary, the present study describes alterations in sex differences in biliary lipid secretion of streptozotocin-induced diabetes. These changes are dependent on the insulin deficiency state rather than on a direct hepatotoxicity of the diabetogenic drug.

The shape of dementia: new measures of morphological complexity in event-related potentials (ERP) and its application to the detection of Alzheimer's disease.

In this paper, we address the problem of quantifying the commonly observed disorganization of the stereotyped wave form of the ERP associated with the P300 component in patients with Alzheimer's disease. To that extent, we propose two new measures of complexity which relate the spectral content of the signal with its temporal waveform: the spectral matching coefficient and the spectral matching entropy. We show by means of experiments that those measures effectively measure complexity and are related to the shape in an intuitive way. Those indexes are compared with commonly used measures of complexity when comparing AD patients against age-matched healthy controls. The results indicate that AD ERP signals are, indeed, more complex in the shape than that of controls, and this result is evidenced mainly by means of our new measures which have a better performance compared to similar ones. Finally, we try to explain this increase in complexity in light of the communication through coherence hypothesis framework, relating commonly found changes in the EEG with our own results.

Non-tuberculous mycobacteria in wild boar (Sus scrofa) from Southern Spain: epidemiological, clinical and diagnostic concerns.

Non-tuberculous mycobacteria (NTM) are widely distributed in the environment, particularly in wet soil, marshland, rivers or streams, but also are causative agents of a wide variety of infections in animals and humans. Little information is available regarding the NTM prevalence in wildlife and their effects or significance in the bovine tuberculosis (bTB) epidemiology and diagnosis. This research shows the most frequently NTM isolated in lymph nodes of wild boar (Sus scrofa) from southern Spain, relating the NTM presence with the individual characteristics, the management of animals and the possible misdiagnosis of Mycobacterium bovis in concurrent infections. A total of 219 NTM isolates were obtained from 1249 wild boar mandibular lymph nodes sampled between 2007 and 2011. All but 75 isolates were identified by the PCR-restriction analysis-hsp65, and a partial sequencing of the 16S rDNA was carried out to identify the rest of the isolates. Results showed that Mycobacterium chelonae was the most frequently isolated NTM specie (133 isolates, 60.7%), followed by Mycobacterium avium (24 isolates, 11%). No relation was found regarding sex, body condition and management, but M. chelonae was more frequently detected in adults, whereas M. avium was more prevalent in subadults. The high NTM prevalence observed in the studied wild boar populations could make difficult the bTB diagnostic.

Thyroid hormones regulate the onset of osmotic activity of rat liver mitochondria after birth.

The effect of thyroid hormone deprivation on the osmotic activity of liver mitochondria from early newborn rats was studied. Experimentally induced hypothyroidism prevented the increase in the osmotic activity of mitochondria observed immediately after birth. Osmotic activity was restored by T4 and T3 treatment to hypothyroid newborns but not when this treatment was supplemented with cycloheximide. Under the same circumstances, streptomycin had no effect. Hypothyroidism abolished the change in the slope of the osmotic curve (plot of inverse absorbance of mitochondrial suspensions incubated in sucrose solutions vs. inverse sucrose concentration) observed in mitochondria from euthyroid newborns at 110-120 mOsm sucrose, suggesting that hypothyroidism prevents the formation of tight physical connections between mitochondrial outer and inner membranes. Thyroid hormone deprivation increased the passive permeability of the mitochondrial inner membrane to protons, resulting in a decreased respiratory control ratio. Hypothyroidism prevented the sharp decrease in the affinity of mitochondria for ATP observed in euthyroid newborns immediately after birth. These results corroborate our previous suggestion (Endocrinology, 1995, 136:4448) that, during the early neonatal period, thyroid hormones control the synthesis of some nucleus-coded protein(s) involved in the assembly of F0,F1-ATPase.

Hypothyroidism prevents postnatal changes in rat liver mitochondrial populations defined by rhodamine-123 staining.

The effect of hypothyroidism on the percentages of low fluorescence population (LFP) and high fluorescence population (HFP) rhodamine-123-stained mitochondria, respiratory parameters, and ATPase activity were studied in liver mitochondria from early newborn rats. Hypothyroidism prevented the decrease in the percentage of HFP and the subsequent increase in LFP that occurs immediately after birth. This effect coincides with the impairment of mitochondrial respiratory function, as shown by the low respiratory control ratio and the low activity of F0,F1-ATPase found in hypothyroid newborns. All of these changes were reversed by the administration of thyroid hormones. ATP in vitro promotes the conversion of HFP into LFP and increases the respiratory control ratio in hypothyroid newborns, although this effect was not observed after thyroid hormone treatment. The effect of thyroid hormones on both the postnatal changes in mitochondrial populations and in F0,F1-ATPase activity was prevented by cycloheximide, but not by streptomycin. Thus, the observed effects of thyroid hormones on neonatal mitochondria must be accomplished by the induction of the synthesis of some nuclei-coded protein, possibly involved in F0,F1-ATPase assembly.

Nitric oxide mediates brain mitochondrial maturation immediately after birth.

The possible role of nitric oxide (*NO) in brain mitochondrial maturation was studied. Within the first 5 min after birth, a sharp increase in ATP concentrations was observed, coinciding with an increase in mitochondrial complex II-III (succinate-cytochrome c reductase) activity, while complex I (NADH-CoQ1 reductase) and complex IV (cytochrome c oxidase) activities remained unchanged. Under the same circumstances, cGMP concentrations were increased by 5 min after birth, correlating significantly with ATP concentrations. Since ATP concentrations also correlated significantly with mitochondrial complex II-III activity, these three parameters may be associated. Inhibition of *NO synthase activity brought about by the administration of N(omega)-nitro-L-arginine monomethyl ester to mothers prevented the postnatal increase in cGMP and ATP levels and complex II-III activity. These results suggest that early postnatal mitochondrial maturation in the brain is a *NO-mediated process.