Evaluation of the effects of chronic occupational exposure to metallic mercury on the thyroid parenchyma and hormonal function.

INTRODUCTION: Experiments in animals exposed to mercury (Hg) in different chemical states have shown thyroid parenchymal and hormone alterations. However, these experiments did not allow the establishment of dose-response curves or provide an understanding of whether these Hg effects on the thyroid parenchyma occur in humans. OBJECTIVE: To evaluate the association between chronic occupational exposure to metallic Hg and alterations in thyroid hormones and gland parenchyma 14 years after the last exposure. METHODS: A cross-sectional study including 55 males exposed in the past to metallic Hg and 55 non-exposed males, paired by age, was conducted in the Hospital das Clínicas (Brazil) from 2016 to 2017. Serum concentrations of total and free triiodothyronine (TT3 and FT3), free thyroxine (FT4), thyrotropin (TSH), reverse T3 (RT3), selenium and antithyroid antibody titers were obtained. The Hg and iodine concentrations were measured in urine. The thyroid parenchyma was evaluated by B-mode ultrasonography with Doppler. The nodules with aspects suspicious for malignancy were submitted to aspiration puncture with a thin needle, and the cytology assessment was classified by the Bethesda system. The t test or Mann-Whitney test, Chi-square test and Spearman correlation were used to compare the exposed and non-exposed groups and examine the relationships between the variables. Univariate and multivariate logistic regression models were used to trace determinants of the risk of thyroid hormone alteration. Statistical significance was defined by p < 0.05. RESULTS: The urinary Hg average was significantly higher in the exposed group than in the non-exposed group (p < 0.01). The mean TSH serum concentration in the exposed group was higher, with a statistically significant difference between the groups (p = 0.03). Serum concentrations of TSH exceeded the normality limit (4.20 µIU/ml) in 13 exposed individuals (27.3%) and 4 non-exposed individuals (7.3%), with a statistically significant association between the hormonal increase and exposure to Hg (p = 0.02). In the logistic regression model, exposure to Hg (yes or no) showed an odds ratio = 4.86 associated with an increase of TSH above the normal limit (p = 0.04). The serum concentrations of RT3 showed a statistically borderline difference between the groups (p = 0.06). There was no statistically significant difference between the mean TT3, FT3 and FT4 serum concentrations in the Hg-exposed group compared to the non-exposed group. The proportions of the echogenicity alterations were higher in the exposed group compared to the non-exposed group (27.3% versus 9.1%; p = 0.03). Papillary carcinomas were documented in three exposed individuals and one non-exposed individual. A follicular carcinoma was recorded in one non-exposed individual. CONCLUSIONS: Due to the higher serum TSH concentration and the prevalence of parenchymal alterations in the Hg-exposed group, even after cessation of exposure, it is recommended that the thyroid status of exposed workers be followed for a long period.

Rnx deficiency results in congenital central hypoventilation.

The genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.

Interaction of methyl-jasmonate and Fusarium poae in bread wheat.

Fusarium Head Blight (FHB) is a devastating disease that affects the grain yield and quality of essential crops such as wheat. In the last years, some Fusarium species have acquired particular importance as Fusarium poae. However, studies to evaluate F. poae-wheat interaction are still scarce. The interaction between F. poae and two bread wheat cultivars with different resistance levels against FHB was evaluated. Moreover, the application of methyl-jasmonate (MeJA) was evaluated as a possible tool to reduce the fungal presence. Our results showed that the MeJA treatment is isolate-dependent, reducing F. poae fungal growth. A decrease in fungal biomass was observed in the susceptible cultivar after MeJA application; however, no differences between inoculated and inoculated-MeJA treatments were observed in the resistant cultivar. Finally, the F. poae inoculation induces the expression of PR1-1 and PDF 1.2, being early in the resistant cultivar compared to the susceptible ones. The application of MeJA combined with the F. poae inoculation increased PR1-1 and PDF1.2 expressions in resistant cultivars. To our knowledge, this is the first study that evaluates the interaction between F. poae and wheat and the MeJA treatment as a possible management strategy against this important pathogen.

An exploratory survey of eating behaviour patterns in adolescent students.

OBJECTIVE: Empirical research has always treated adolescents' eating habits from a variable-centered perspective, but this approach may miss the configurations of eating behaviours that uniquely describe discrete groups of individuals. The aim of this study was to investigate prototypical patterns of eating habits in a large sample of Italian adolescents and their behavioural and psychological correlates. METHOD: Data were gathered from 1388 students (F=60%, mean age 14.90±1.34 yrs), who were asked to fill in an original questionnaire surveying dietary habits, body weight attitudes, body image, sport activities and sources of information about food. Perfectionism, self-esteem, self-efficacy and care for food were also assessed as well-known psychological risk factors for Eating Disorders. RESULTS: Five prototypical eating behaviour patterns were identified through cluster analysis. Cluster membership was associated (p<0.05) with gender, age and age- and gender-correct BMI percentile, perceived relevance of physical appearance in achieving success in life; one's weight and body image evaluation, dieting, physical activity, self-efficacy, self-esteem and care for food. Clusters did not differ in perfectionism score and in frequency of consulting different sources of information about food and weight, except in the case of dieticians. CONCLUSION: The identification of prototypical eating habits patterns revealed a large range of wrong eating attitudes and behaviours among Italian adolescents. Such data suggest the need to develop and implement adequate prevention programs.

Respiratory activity in brainstem of fetal mice lacking glutamate decarboxylase 65/67 and vesicular GABA transporter.

The respiratory neural network in the mammalian medulla oblongata shows rhythmic activity before birth. GABA and glycine are considered to be involved in control of respiratory rhythm. Recently we have demonstrated respiratory failure in glutamic acid decarboxylase (GAD) 67-deficient mice [Tsunekawa N, Arata A, Obata K (2005) Development of spontaneous mouth/tongue movement and related neural activity, and their repression in mouse fetus lacking glutamate decarboxylase 67. Eur J Neurosci 21:173-178]. To further evaluate the involvement of GABA and glycine in fetal respiratory function, we studied neural activities in brainstem-spinal cord blocks prepared from GAD65-/-:67-/- and vesicular GABA transporter (VGAT)-/-mice on embryonic day 14 (E14)-E15 and E18. In these knockout mice, the synthesis of GABA and the vesicular release of GABA and glycine are completely absent, respectively. Spontaneous respiratory discharges were observed in the ventral roots at the cervical cord (C) 4 level from wild-type mice but not from the knockout mice on E18. Administration of substance P induced C4 discharges in GAD65-/-:67-/- preparations but not in VGAT-/- preparations. C4 discharges were observed in the knockout mice on E14-E15, although the frequency was lower than that in the wild-type. Neuronal activities in the respiratory network of the E18 brainstem were recorded using a "blind" patch-clamp technique. Expiratory and inspiratory neurons with their characteristic firing patterns were observed in the wild-type fetuses. Strychnine reversed inspiratory-phase hyperpolarization to large depolarization in expiratory neurons. On the other hand, neurons in the same area of the knockout mice fired spontaneously without any rhythm. Substance P induced hyperpolarizing potentials in medullary neurons of GAD65-/-:67-/- mice. Further administration of strychnine induced large depolarizing potentials. Rhythmic activities were not observed in VGAT-/- mice even in the presence of substance P and strychnine. These results indicate that the lack of GABA and glycine impairs the function of the respiratory network in mouse fetuses and the impairment progresses with fetal age.

Possible synaptic connections of expiratory neurons in the medulla of newborn rat in vitro.

To elucidate synaptic interactions between expiratory (Exp) and other respiratory neurons in the ventrolateral medulla of brain stem-spinal cord preparations from newborn rats, we analyzed postsynaptic potentials in Exp and a subclass of inspiratory (Insp) neurons using whole-cell recordings. About 72% of the Exp neurons (Exp-p-i) showed Cl--dependent synaptic inhibition during the Insp and pre/post-Insp phases, corresponding to the active phase of the Insp and pre-inspiratory (Pre-I) neurons, respectively. The other 28% neurons (Exp-i) received Cl--dependent inhibition during the Insp phase only. Some Insp neurons showed reversed IPSPs during the active phase of Exp-p-i after Cl-loading. We suggest the existence of inhibitory connections from Pre-I and Insp to Exp and from Exp to Insp neurons. Basic synaptic connections among respiratory neurons similar to those in intact adult mammals may already exist in newborn rats.

Difficulties facing vector control in the 1990s.

Financial and technical support for vector control programs in developing countries have been reduced over the past decades. The cost of insecticides and environmental concerns are given as major reasons, but competition for the same resources with other important health problems is also a factor. This paper reviews some of the difficulties, especially managerial, that presently face vector control programs in developing countries. The need for vector control to expand beyond insecticide application and to develop approaches that require collaboration with other economic sectors and governmental agencies outside the health sector are discussed.

Primary respiratory rhythm generator in the medulla of brainstem-spinal cord preparation from newborn rat.

It has been previously demonstrated that rhythmically firing neurons (Pre-I neurons) preceding cervical root (C4 or C5) inspiratory activity, localized in the rostral ventrolateral medulla (RVL), are important in the generation of the basic respiratory rhythm in brainstem-spinal cord preparations from newborn rats. We examined the effects of single and continuous electrical stimulation applied to the RVL on Pre-I and C4 activities in these preparations. We verified that the phase of respiratory rhythm was reset when Pre-I firing was induced in both right and left RVL by single shock stimulation, whether C4 activity appeared or not. Lower frequency and intensity of continuous pulse train stimulation in the RVL enhanced Pre-I activity, and hence C4 activity, whereas higher frequency and intensity inhibited both. The results suggest that synchronous burst activity between the right and left Pre-I neurons must be above a certain level (in its intraburst firing rate) to trigger C4 inspiratory activity and, therefore, that cooperation among Pre-I neurons is important for induction of rhythmic inspiratory drive. After bilateral lesions of the caudal ventrolateral medulla, Pre-I neurons retained their rhythmic activity, while C4 activity disappeared. Present results further confirmed our hypothesis that Pre-I neurons are the primary generator of respiratory rhythm. We propose a hypothetical model of the generation of rhythmic respiratory activity.

Effects of cAMP on respiratory rhythm generation in brainstem-spinal cord preparation from newborn rat.

Involvement of cAMP in the generation of respiratory rhythm was studied in newborn rat brainstem-spinal cord preparations. The respiratory rhythm was monitored by C4 inspiratory activity and/or pre-inspiratory (Pre-I) activity of neurons in the rostral ventrolateral medulla; previously suggested to be primary rhythm generating neurons which have pacemaker properties. The effects of four cAMP-increasing agents (forskolin, IBMX, Db-cAMP, and 8-Br-cAMP) on this neuronal activity were examined. Perfusion with forskolin (3-10 microM) increased the burst rate of C4 inspiratory activity in 20 of 32 preparations, but in 8 of those the increase was preceded by transient depression. The facilitation of the respiratory rhythm was greater whenever the burst rate before forskolin treatment was lower. The Pre-I neuron burst rate, which was recorded together with C4 activity, predominantly increased with forskolin treatment. The effects of IBMX, Db-cAMP and 8-Br-cAMP were similar to those of forskolin, but they were slightly less potent. Long-lasting depression of the respiratory rhythm (C4 and Pre-I activity) by clonidine, which might decrease intracellular cAMP level via alpha 2-receptors, was reversed by forskolin. To investigate the direct effects of the cAMP-increasing agents on Pre-I neurons, Pre-I activity was isolated by blocking the chemical synaptic transmission by incubation in a low Ca solution (0.2 mM Ca2+, 5 mM Mg2+). Forskolin (5-10 microM), IBMX (5-10 microM), Db-cAMP (0.2-0.4 mM), and 8-Br-cAMP (0.4-0.75 mM) all enhanced the burst rate of isolated Pre-I neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of respiratory rhythm-generating neurons in the medulla of brainstem-spinal cord preparations from newborn rats.

We describe the location of Pre-I neurons, which are important to respiratory rhythm generation, in the rostral medulla of brainstem-spinal cord preparations isolated from newborn rats. This neuronal group was delimited in the reticular formation slightly medial to the caudal area of the facial nucleus and near the ventral surface. The effects of electrical stimulation and lesions in that region were also examined with respect to respiratory rhythm generation. Single shock stimulation induced Pre-I neuron firing and reset the phase of the respiratory rhythm. Electrolytic lesions in the Pre-I neuron region reduced the respiratory rate.

Possible mutual excitatory couplings between inspiratory neurons in caudal ventrolateral medulla of brainstem-spinal cord preparation isolated from newborn rat.

In in vitro brainstem-spinal cord preparations, projection of inspiratory neurons in the caudal ventrolateral medulla (CVL) was examined electrophysiologically, and connectivity between bilateral inspiratory neurons in the CVL was analyzed by pulse-cross correlation (PCC) analysis. CVL inspiratory neurons were found to project to the contralateral CVL and/or mainly ipsilateral spinal cord. PCC analysis revealed significant peaks with different latency on both sides of time zero in 3 of 8 pairs. Results were consistent with mono- or oligo-synaptic excitatory connections between bilateral inspiratory neurons in the CVL.

Activity of rat pump neurons is modulated with central respiratory rhythm.

The firing properties of the second-order neurons of the slowly-adapting pulmonary stretch receptors called pump neurons (P-cells), were studied in Nembutal-anesthetized, paralyzed, and artificially-ventilated rats. Extracellular recording was made from single P-cells which were monosynaptically activated by electrical stimulation of the vagal afferents and fired in phase with lung inflations. In the majority of the P-cells examined (49/52), the firing was suppressed to various extents in the inspiratory phase: in effect, their firing was accentuated at the time of the inspiratory off-switch. This issue has never been reported in cat P-cells, on which relatively rich data have been accumulated. The present results suggest that rat P-cells do not only relay information from the lung stretch receptors but also integrate the central respiratory inputs.

Respiration-related neurons in the ventral medulla of newborn rats in vitro.

In brainstem-spinal cord preparations isolated from newborn rats, we examined functions of the ventral medulla in respiratory rhythm generation, and located respiratory neurons in that region. Removal of the dorsal half of the medulla caused only modest reduction of the rate of inspiratory bursts from the cervical (C4 or C5) ventral root and moderate changes in the burst pattern. We describe here two types of respiratory neurons; Pre-I neurons that are presumably crucial in primary rhythm generation, and inspiratory (I) neurons that we presume to be important in inspiratory pattern generation. Pre-I neurons were located close to phenylethanolamine N-methyltransferase (PNMT)-immunoreactive (IR) neurons that are common in the reticular formation of the rostral ventrolateral medulla (RVL). Distributions of I neurons and Pre-I neurons overlapped in the RVL, and I neurons were also near the nucleus ambiguus in the more caudal part of the ventrolateral medulla. The results indicate that the ventral medulla is essential to inspiratory pattern generation as well as rhythm generation. It is suggested that the RVL is an important site in rhythm generation. The region of inspiratory pattern generation may extend more caudally in the ventral medulla.

Multiplex polymerase chain reaction for distinguishing Taylorella equigenitalis from Taylorella equigenitalis-like organisms.

It is difficult to distinguish isolates of Taylorella equigenitalis, the cause of contagious equine metritis, from a T. equigenitalis-like organism isolated from asymptomatic donkeys and horses. Although T. equigenitalis is responsible for a severe, contagious disease of the reproductive tract of equids, the T. equigenitalis-like organism, although contagious, does not appear to produce disease. Because of the economic consequences of correctly distinguishing isolates of these 2 microorganisms, a polymerase chain reaction (PCR)-based assay was developed that will distinguish isolates of T. equigenitalis from the T. equigenitalis-like microorganism. The primers used in the PCR assay were designed to amplify unique regions of the gene encoding the 16S ribosomal RNA.

Neuronal mechanisms of respiratory rhythm generation: an approach using in vitro preparation.

The respiratory network in the ventrolateral medulla of the brainstem-spinal cord preparation from newborn rat involves pre-inspiratory (Pre-I) neurons, three types of inspiratory (Insp I, II, III) neurons and two types of expiratory (Exp-i, Exp-p-i) neurons as major subtypes, which were classified according to patterns of postsynaptic potentials. The neuronal respiratory-related membrane potential fluctuations of these cells indicate at least four distinguishable phases of the in vitro respiratory cycle: pre-inspiratory, inspiratory, post-inspiratory (E1), and late-expiratory (E2). A current hypothesis for the central pattern generator of respiration proposed by our group is that Pre-I neurons in the rostral ventrolateral medulla, with intrinsic burster properties, produce the primary respiration rhythm. This rhythm triggers an inspiratory pattern generator composed of Insp neurons in the rostral and caudal ventrolateral medulla. Respiratory neurons possess several types of ionic channels which are involved in the generation of rhythm and burst pattern. Particularly, P-type Ca2+ channels and TTX-sensitive persistent Na+ channels are postulated to contribute to the intrinsic burst generation of Pre-I neurons. N-type Ca2+ channels may be involved in the maintenance and termination of inspiratory burst activity via the activation of Ca2(+)-dependent K+ channels. Respiratory neuron networks in this preparation were compared with those of different in vitro preparations, like rhythmic slices or perfused brainstems and of adult mammals in vivo. Many types of synaptic connections among respiratory neurons in adult mammals were also found in the (rostral) ventrolateral medulla of a brainstem-spinal cord preparation from newborn rat. The characteristics of the inspiratory burst pattern and inspiratory off switch mechanisms in newborn rat preparations might be explained by insufficient inhibitory (or excitatory) synaptic inputs to the inspiratory pattern generator due to an immature neuron network and/or deafferentiation.

A case of primary retroperitoneal mucinous cystadenocarcinoma.

A rare case of primary retroperitoneal mucinous cystadenocarcinoma in a 44-year-old woman is reported. The cystic tumor was delineated by CT and echography. The tumor was removed intact in the presence of bilateral normal ovaries and demonstrated an infiltrating malignant process. This neoplasm may have arisen from a supernumerary ovary. The patient died of recurrence 4 months after surgery. A comparison of the known cases indicates that aggressive treatment by hysterectomy with bilateral salpingo-oophorectomy in addition to cyst extirpation may improve prognosis.

[Clinical evaluation and therapeutic strategy in necrotizing fasciitis or Fournier's syndrome. 2 case reports]. / Valutazione clinica e strategia terapeutica della fascite necrosante o sindrome di fournier. Presentazione di due casi clinici.

Fournier's syndrome or necrotizing fasciitis is a rare infection with high mortality rate. Old patients especially with diabetes mellitus, liver and renal failure are more affected. This disease requires prompt treatment: early diagnosis, antibiotic therapy, nutritional support and immediate extensive surgical debridement are necessary. Two clinical cases are presented.

[Perforation of primary non-Hodgkin's lymphoma during chemotherapy. Clinical evaluation and therapeutic strategy]. / Perforazione di linfoma non-Hodgkin del cieco dopo chemioterapia. Valutazione clinica e strategia terapeutica.

Primary cecal lymphoma are very rare. The case is reported of an elderly woman having voluntary preliminary chemotherapy with consequent cecum perforation due to tumoral necrosis, some days after the first chemotherapy. The diagnostic, clinical and therapeutic protocol is analysed and stress is laid on the rare clinical cases described. Resection is advisable in the still delimited forms in order to avoid surgical complications due to preliminary chemotherapy and in order to classify precisely the neoplasm.

Quantitative phase analysis from X-ray diffraction in Y-TZP dental ceramics: a critical evaluation.

UNLABELLED: The dentistry literature shows consensus to use the Garvie and Nicholson equation modified by Toraya to quantify the Y-TZP phase transformation. However, this method does not include the possibility of cubic phase transformation and crystallographic texture after artificial ageing, and in this case, it is possible to observe errors of quantification. OBJECTIVES: The aim of this study was to evaluate a dental Y-TZP ageing kinetic of phase transformation under pressure and hydrothermal conditions (130°C, 2bar) and to compare the methods of quantification by the equation of Garvie and Nicholson modified by Toraya and the Rietveld refinement method. METHODS: Discs of Y-TZP (12mm Ø×1.2mm in height) were divided into groups (n=4) according to the ageing times (in the range of 6 and 138h). The superficial characterisation was made using SEM and the XDR for crystallographic analysis. RESULTS: An aggressive superficial degradation process at the beginning of phase transformation in 6-10h of ageing was observed by SEM. The phase transformation quantification showed differences between the methods. It was observed the increase and stabilisation of monoclinic phase until 80% at 40h of ageing by the Garvie and Nicholson modified by Toraya equation, compared to 60% of monoclinic phase and approximately 30% of cubic phase observed by the Rietveld method. CONCLUSION: The Toraya equation showed an overestimated result of monoclinic quantification compared to the Rietveld method. CLINICAL SIGNIFICANCE: The overestimated result of monoclinic phase could lead to different interpretation about the dental Y-TZP ageing process.