Effects of bilateral adrenalectomy on systemic kainate-induced activation of the nucleus of the solitary tract. Regulation of blood pressure and local neurotransmitters

Glutamatergic transmission through metabotropic and ionotropic receptors, including kainate receptors, plays an important role in the nucleus of the solitary tract (NTS) functions. Glutamate system may interact with several other neurotransmitter systems which might also be influenced by steroid hormones. In the present study we analyzed the ability of systemic kainate to stimulate rat NTS neurons, which was evaluated by c-Fos as a marker of neuronal activation, and also to change the levels of NTS neurotransmitters such as GABA, NPY, CGRP, GAL, NT and NO by means of quantitative immunohistichemistry combined with image analysis. The analysis was also performed in adrenalectomized and kainate stimulated rats in order to evaluate a possible role of adrenal hormones on NTS neurotransmission. Male Wistar rats (3 month-old) were used in the present study. A group of 15 rats was submitted either to bilateral adrenalectomy or sham operation. Forty-eight hours after the surgeries, adrenalectomized rats received a single intraperitoneal injection of kainate (12 mg/kg) and the sham-operated rats were injected either with saline or kainate and sacrificed 8 hours later. The same experimental design was applied in a group of rats in order to register the arterial blood pressure. Systemic kainate decreased the basal values of mean arterial blood pressure (35%) and heart rate (22%) of sham-operated rats, reduction that were maintained in adrenalectomized rats. Kainate triggered a marked elevation of c-Fos positive neurons in the NTS which was 54% counteracted by adrenalectomy. The kainate activated NTS showed changes in the immunoreactive levels of GABA (143% of elevation) and NPY (36% of decrease), which were not modified by previous ablation of adrenal glands. Modulation in the levels of CGRP, GAL and NT immunoreactivities were only observed after kainate in the adrenalectomized rats. Treatments did not alter NOS labeling. It is possible that modulatory function among neurotransmitter systems in the NTS might be influenced by steroid hormones and the implications for central regulation of blood pressure or other visceral regulatory mechanisms control should be further investigated.

Adrenalectomy counteracts the local modulation of astroglial fibroblast growth factor system without interfering with the pattern of 6-OHDA-induced dopamine degeneration in regions of the ventral midbrain

The present study investigated the effects of bilateral adrenalectomy (ADX) on the synthesis of basic fibroblast growth factor (bFGF, FGF-2) mRNA and on the expression of its FGF receptor subtype-2 (FGFR2) mRNA after a 6-hydroxydopamine (6-OHDA)-induced lesion of nigrostriatal dopamine system. In previous papers we have demonstrated that corticosterone increases FGF-2 immunoreactivity mainly in the astrocytes of the substantia nigra [Chadi, G., Rosen, L., Cintra, A., Tinner, B., Zoli, M., Pettersson, R.F., Fuxe, K., 1993b. Corticosterone increases FGF-2 (bFGF) immunoreactivity in the substantia nigra of the rat. Neuroreport 4, 783-786.] and that 6-OHDA injected in the ventral midbrain upregulates FGF-2 synthesis in reactive astrocytes in the ascending dopamine pathways [Chadi, G., Cao, Y., Pettersson, R.F., Fuxe, K., 1994. Temporal and spatial increase of astroglial basic fibroblast growth factor synthesis after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons. Neuroscience 61, 891-910.]. Rats were adrenalectomized and received a 6-OHDA stereotaxical injection in the ventral midbrain 2 days later. Seven days after the dopamine lesion, Western blot analysis showed a decreased level of tyrosine hydroxylase in the lesioned side of the midbrain, an event that was not altered by ADX or corticosterone replacement. Moreover, the degeneration of nigral dopamine neurons, which was confirmed by the disappearance of acidic FGF (FGF-1) mRNA and the decrement of tyrosine hydroxylase mRNA labeled nigral neurons, was not altered by ADX. The FGF-2 protein (23 kDa isoform but not 21 kDa fraction) levels increased in the lesioned side of the ventral midbrain. This elevation was counteracted by ADX, an effect that was fully reversed by corticosterone replacement. In situ hybridization revealed that ADX counteracted the elevated FGF-2 mRNA levels in putative glial cells of the ipsilateral pars compacta of the substantia nigra and in the ventral tegmental area. The ADX also counteracted the increased density and intensity of the astroglial FGF-2 immunoreactive profiles within the lesioned pars compacta of the substantia nigra and the ventral tegmental area as determined by stereology. The stereotaxical mechanical needle insertion triggered the expression of FGFR2 mRNA in putative glial cells, spreading to the entire ipsilateral ventral midbrain from the region of needle track, an occurrence that was partially reversed by ADX. In conclusion, bilateral ADX counteracted the increased astroglial FGF-2 synthesis in the dopamine regions of the ventral midbrain following a 6-OHDA-induced local lesion and interfered with FGF receptor regulation around injury. These findings give further evidence that adrenocortical hormones may regulate the astroglial FGF-2-mediated trophic mechanisms and wound repair events in the lesioned central nervous system. (c) 2007 Elsevier B.V. All rights reserved.

HER2 Testing in Breast Carcinoma Very Low Concordance Rate Between Reference and Local Laboratories in Brazil

Breast cancer accounts for approximately one quarter of all cancers in females. HER2 gene amplification or HER2 protein overexpression, detected in about 20% of breast carcinomas, predicts a more aggressive clinical course and determines eligibility for targeted therapy with trastuzumab. HER2 testing has become an essential part of the clinical evaluation of all breast carcinoma patients, and accurate HER2 results are critical in identifying patients who may be benefited from targeted therapy. This study investigated the concordance in the results of HER2 immunohistochemistry assays performed in 500 invasive breast carcinomas between a reference laboratory and 149 local laboratories from all geographic regions of Brazil. Our results showed an overall poor concordance (171 of 500 cases, 34.2%) regarding HER2 results between local and reference laboratories, which may be related to the low-volume load of HER2 assays, inexperience with HER2 scoring system, and/or technical issues related to immunohistochemistry in local laboratories. Standardization of HER2 testing with rigorous quality control measures by local laboratories is highly recommended to avoid erroneous treatment of breast cancer patients.

CO(2) Abdominal Insufflation Decreases Local and Systemic Inflammatory Response in Experimental Acute Pancreatitis

Objectives: Acute pancreatitis (AP) is a serious disease that is amplified by an associated systemic inflammatory response. We investigated the effect of CO(2) pneumoperitoneum on the local and systemic inflammatory response in AP. Methods: Acute pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection. Carbon dioxide pneumoperitoneum was applied for 30 minutes before the induction of AP. Inflammatory parameters were evaluated in the peritoneum (ascites, cell number, and tumor necrosis factor alpha [TNF-alpha]), serum (amylase, TNF-alpha, interleukin-6 [IL-6], and IL-10), pancreas (myeloperoxidase [MPO] activity, cyclooxygenase 2 and inducible nitric oxide synthase expression, and histological diagnosis), liver, and lung (mitochondria dysfunction and MPO activity). Results: Abdominal insufflation with CO(2) before induction of AP caused a significant decrease in ascites volume, cells, and TNF-alpha in the peritoneal cavity and in serum TNF-alpha and IL-6 but not IL-10 levels. In the pancreas, this treatment reduced MPO activity, acinar and fat necrosis, and the expression of inducible nitric oxide synthase and cyclooxygenase 2. There were no significant differences on serum amylase levels, liver mitochondrial function, and pulmonary MPO between groups. Conclusions: Our data demonstrated that CO(2) pneumoperitoneum reduced pancreatic inflammation and attenuated systemic inflammatory response in AP. This article suggests that CO(2) pneumoperitoneum plays a critical role on the better outcome in patients undergoing laparoscopic pancreatic surgery.

Local renin-angiotensin system regulates left ventricular hypertrophy induced by swimming training independent of circulating renin: a pharmacological study

Introduction. This study addressed the role of the local renin-angiotensin system (RAS) in the left ventriular hypertropy (LVH) induced by swimming training using pharmacological blockade. Materials and methods. Female Wistar rats treated with enalapril maleate (60 mg.kg(-1).d(-1), n = 38), losartan (20 mg.kg(-1).d(-1), n = 36) or high salt diet (1% NaCl, n = 38) were trained by two protocols (T1: 60-min swimming session, 5 days per week for 10 weeks and T2: the same T1 protocol until the 8(th) week, then 9(th) week they trained twice a day and 10(th) week they trained three times a day). Salt loading prevented activation of the systemic RAS. Haemodynamic parameters, soleus citrate synthase (SCS) activity and LVH (left ventricular/body weight ratio, mg/g) were evaluated. Results. Resting heart rate decreased in all trained groups. SCS activity increased 41% and 106% in T1 and T2 groups, respectively. LVH was 20% and 30% in T1 and T2 groups, respectively. Enalapril prevented 39% of the LVH in T2 group (p < 0.05). Losartan prevented 41% in T1 and 50% in T2 (P < 0.05) of the LVH in trained groups. Plasma renin activity (PRA) was inhibited in all salt groups and it was increased in T2 group. Conclusions. These data provide evidence that the physiological LVH induced by swimming training is regulated by local RAS independent from the systemic, because the hypertrophic response was maintained even when PRA was inhibited by chronic salt loading. However, other systems can contribute to this process.

Systemic and Local Inflammation in Peritoneal Dialysis: Mechanisms, Biomarkers and Effects on Outcome

Thanks to the technological development in peritoneal dialysis (PD) during the last three decades, the most important problem nowadays for the nephrologists is the maintenance of the long-term function of the peritoneal membrane. Although PD may exert an early survival benefit as compared with hemodialysis (HD), long-term PD is often associated with histopathological alterations in the peritoneal membrane that are linked to peritoneal ultrafiltration deficit and increased mortality risk. These alterations are closely related to the presence of a chronic activated (local and systemic) inflammatory response. PD itself may have other factors associated that could further modulate the inflammatory response, such as the bioincompatibility of dialysis solutions, fluid overload and changes in the body composition. Understanding the pathophysiology of inflammation in PD is essential for the adoption of adequate strategies to improve both membrane and patient survival. Copyright (C) 2009 S. Karger AG, Basel

LOCAL LOW POWER LASER IRRADIATION ACCELERATES THE REGENERATION OF THE FIBULAR NERVE IN RATS

Objective: To study the influence of low power GaAsAl laser irradiation on the regeneration of a peripheral nerve, following a controlled crush injury. Material and methods: The right common fibular nerve of 30 Wistar rats was submitted to a crush injury with an adjustable load forceps (5 000 g, 10 minutes of application). The animals were divided into three groups (n=10), according to the postoperative procedure (no irradiation; sham irradiation; effective irradiation). Laser irradiation (830 nm wave-length; 100 mW emission power; continuous mode; 140 J/cm(2)) was started on the first postoperative day and continued over 21 consecutive days. Body mass, time spent on the walking track and functional peroneal index (PFI) were analyzed based on the hind footprints, both preoperatively and on the 21st postoperative day. Results: Walking time and PFI significantly improved in the group that received effective laser irradiation, despite the significant gain in body mass between the pre- and post-operative periods. Conclusion: Low Power GaAsAl laser irradiation, with the parameters used in our study, accelerated and improved fibular nerve regeneration in rats.