Somatosensory cortectomy induces motor cortical hyperexcitability and scoliosis: an experimental study in developing rats

Background contextDysfunctions in sensorimotor integration, reminiscent to those described in idiopathic dystonia, have been found in idiopathic scoliosis (IS) and might be involved in its pathogenesis. Studying the effects of experimental disruption of sensory cortex may shed further insight into the etiopathology of IS.PurposeTo evaluate whether disruption of central sensorimotor integration through partial ablation of the somatosensory cortex leads to scoliosis in developing rats and to describe the effects of such an intervention on motor cortico-cortical inhibition and facilitation.MethodsFifty Wistar rats aged 3 weeks were used in the study. Twenty-four rats underwent craniotomy and electrocoagulation of the sensory cortex (PAR1) in the right hemisphere. A second group of 16 rats underwent a sham operation with craniotomy but no electrocoagulation. A third group of 10 rats was used as intact controls. Four weeks after surgery, motor cortical excitability was assessed with paired-pulse electrical cortical stimulation. Neurologic and behavioral examinations were completed serially, and 10 weeks after surgery, X-ray examinations were performed in anesthetized rats to assess spinal curvature. Electromyographic recordings of paravertebral muscle activity were performed in waking rats. At the end of the study, rats were sacrificed, and histologic examinations of brain tissue were performed to confirm the extent of the lesion. A grant from a Government Health Research Fund without salaries assignment financed the study.ResultsAlmost half of the animals with somatosensory cortectomy (46%) developed scoliosis, with an average Cobb angle of 23±8°. None of the animals in the sham or control groups developed scoliosis. Despite cortical lesions, no motor or behavioral deficits were apparent in the experimental group, and cortectomized rats were neurologically indistinguishable from sham or control animals, except for the presence of scoliosis. Cortico-cortical inhibition was significantly reduced in the hemisphere of scoliotic concavity in the cortectomized group but was normal in the other groups.ConclusionsThese findings indicate that altered sensorimotor integration may cause scoliosis without noticeable motor impairment. Reduced cortico-cortical inhibition was observed in cortectomized rats. This finding is consistent with results in adolescents with IS and suggests that alteration of cortical hemispheric balance of sensorimotor integration may play an important role in the pathogenesis of IS.     

Possible Allergenic Role of Tropomyosin in Patients with Adverse Reactions after Fish Intake

In a recent case report, patient’s anti-fish tropomyosin IgE was associated with gastrointestinal symptoms. We aimed to demonstrate on a wider scale that the panallergen tropomyosin should not be limited to invertebrate species and that clinically relevant reactions could be elicited by vertebrate tropomyosin. On the whole, 19 patients with adverse reactions after fish intake and showing negative skin tests with commercial fish extracts were included. Fish tropomyosin was recognized by 10/19 patients’ IgE by immunoblotting. All patients with gastrointestinal complaints after fish intake (6/6) showed an IgE band matching with tropomyosin. Cod, albacore, and swordfish tropomyosins were recognized by most patients although 3/10 patients did not claim adverse reactions to these fish species. Immunoblotting with a battery of antigens from different fish species have a high yield of positivity at a band matching with tropomyosin molecular weight, even if they have not been claimed to be causative agents of symptoms. Tropomyosin is therefore a good candidate to be investigated as a clinically relevant fish allergen in patients who report adverse reactions after fish intake.     

Protein-caloric food restriction affects insulin-like growth factor system in fetal Wistar rat

We have previously shown that fetuses from protein-caloric undernourished pregnant rats (35% of control diet during the last week of pregnancy) at 21.5 d post coitum exhibit increased beta-cell mass. This alteration is correlated with increased insulinemia and total pancreatic insulin content, a pattern similar to that reported in infants of mild diabetic mothers. In this work, we investigated in undernourished fetuses: 1) whether availability of growth factors such as insulin, GH, and IGFs and their binding proteins (IGFBPs) could be implicated in this alteration, and 2) the beta-cell mitogenic response to IGFs in vitro. The results show that maternal undernutrition increases pancreatic IGF-I expression and islet IGF-I receptor content in undernourished fetuses, whereas hepatic IGF-I expression and serum IGF-I levels were decreased. No changes were observed in serum IGF-II, and its expression was diminished in undernourished pancreases and unchanged in the liver, compared with control fetuses. Serum levels and liver and pancreatic mRNA expression of IGFBP-1 were found to be normal in undernourished fetuses, whereas the serum concentration and abundance of IGFBP-2 mRNA in pancreas were increased. Finally, the beta-cell mitogenic response to IGFs in vitro was significantly increased in undernourished fetal islets, compared with controls. In conclusion, in undernourished fetuses the increased beta-cell mass can be related to the stimulation of replicative beta-cell response due to locally increased pancreatic IGF-I mRNA; this effect is perhaps potentiated or favored by the enhanced islet IGF-I receptor content and pancreatic IGFBP-2 gene expression.     

The influence of polymorphisms of VKORC1 and CYP2C9 on major gastrointestinal bleeding risk in anticoagulated patients

The VKORC1 c.-1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty-nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4.19 (1.59-11.04)]; amiodarone use [adjusted OR (95% CI) = 9.97 (1.75-56.89)]; or aspirin use [adjusted OR (95% CI) = 8.97 (1.66-48.34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0.50 (0.26-0.99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin.     

Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

PURPOSE: Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer.METHODS: This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test.RESULTS: Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11–160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients (P = 0.489).CONCLUSIONS: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.Supported by the Apertus Research Program (Andromaco Pharmaceutical Company) and by The National Public Grant (FONDECYT #1000556).