Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.     

The Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease.

Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in recognition of, and subsequent immune response activation against, mycobacteria. The genetic polymorphism of TLR2 (arginine to glutamine substitution at residue 753 (Arg753Gln)) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to mycobacteria. The aim of the present study was to investigate the Arg753Gln single nucleotide polymorphism of the TLR2 gene in tuberculosis (TB) patients compared to healthy controls. A retrospective case/control study was carried out. The Arg753Gln polymorphism of the TLR2 gene was studied in 151 TB patients compared to 116 ethnically and age-matched healthy control subjects. The TLR2 polymorphism (adenine (A) allele) was observed in 17.9 and 7.7% of TB patients and controls, respectively. When the ratios of the three genotypes were compared between the two groups, the AA genotype was found to be more significantly associated with TB. Allele frequencies for guanine (G) and A were found to be 0.95 and 0.05 in the control group and 0.86 and 0.14 in the TB patient group, respectively. The risk of developing TB disease was increased 6.04- and 1.60-fold for carriers of the AA and GA genotypes, respectively. In conclusion, the present data suggest that the arginine to glutamine substitution at residue 753 polymorphism of the Toll-like receptor 2 gene influences the risk of developing tuberculosis.     

Prefabrication of bone by vascular induction: an experimental study in rabbits.

The various methods of prefabricating flaps include vascular induction through staged transfer; pretransfer delay, expansion, and grafting; the use of alloplastic materials; and tissue bioengineering. In this experimental study, vascular induction was used to provide an axial vascular pedicle to randomly nourished tissue. Twenty-six New Zealand rabbits, ages and weights ranging between 6 months-1 year and 1.5-3.5 kg, respectively, were used. The sex difference was not considered. The deep inferior epigastric artery and vein were used to carry blood and were placed into a segment of femur to prefabricate the bone. Four weeks later, the viability of the segment of bone prefabricated by new axial pedicle was shown by scintigraphic study, and the new axial pedicle was ready for free transfer.     

Percutaneous radiofrequency rhizotomy of lumbar spinal facets: The results of 46 cases

The results of percutaneous radiofrequency rhizotomy of lumbar spinal facets in 46 patients followed at least three months (mean 15 months) are reported and compared with those reported previously. Satisfactory pain relief three months after the procedure was achieved in 36.4 percent of patients without operations and in 41.7 percent of patients with operations other than fusion.No patient had previously undergone fusion.Treatment of low-back pain by using radio-frequency thermocoagulation of spinal facets is a simple, safe, and well-tolerated procedure. It can be used to relief of pain in spite of decreasing rates of success within the follow-up period.     

Anticonvulsive effects of quinine on penicillin-induced epileptiform activity: an in vivo study.

Epilepsy is an important problem in neurological disorders. The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. Recent studies claimed that gap junctions have a critical role in epileptic neuronal events. The aim of present study is to investigate the effects of connexin36 (Cx36) channel blocker quinine on penicillin-induced experimental epilepsy. For this purpose, 4 months old male Wistar rats were used in the present study. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. At the end of the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When the epileptiform activity, monitored from a digital recording system, reached maximal frequency and amplitude, quinine (200, 400 or 1000 nmol) was administered similar to penicillin. Effects of quinine on epileptiform activity were assessed by both electrophysiological and behavioral analysis. Quinine suppressed epileptiform activity by decreasing the amplitude and frequency of epileptiform spikes and by attenuating the epileptiform behavior. The outcomes of this study suggest that the blockade of Cx36 channels may contribute to the amelioration of epileptic activity.     

Does gastric adenocarcinoma develop after the treatment of gastric lymphoma?

Two adult patients with the diagnosis of gastric lymphoma who developed adenocarcinoma of the stomach 8 years after the treatment are presented. Both patients were treated by subtotal gastrectomy followed by irradiation of 4,000–4,500 cGy to the epigastric region and six courses of chemotherapy (vincristine, cyclophosphamide, prednisolone). In our review of the literature, 16 cases of gastric adenocarcinoma following the treatment of gastric lymphoma were found and listed with details. The factors influencing the development of this secondary carcinoma, mainly those treatment related are discussed. The possible role of both radiotherapy and chemotherapy in shortening the latent period for the development of stump carcinoma is emphasized. © 1993 Wiley-Liss, Inc.     

Giant fusiform aneurysm of the vertebro-basilar artery presenting with stroke

The authors describe a case of giant fusiform aneurysm of the basilar artery presenting with ischemic symptoms. Angiography and CT revealed vertebro-basilar fusiform aneurysmal dilatation. Fusiform vertebro-basilar ancurysm is associated with various complications particularly brain stem infarction. Similar lesions in the literature are reviewed and the relationship between this clinical entity and cerebral ischemia, particularly brainstem infarction are discussed.     

In the hippocampus in vivo,nitric oxide does not appear to function as an endogenous antiepileptic agent

Using a reverberatory epilepiform discharge of hippocampal-parahippocampal circuits termed maximal dentate activation, this study investigated whether the local release of nitric oxide within these circuits functions as an antiepileptic agent. Two nitric oxide synthase inhibitors (l-nitro-arginine methyl ester and 7-nitro-indazole) and a guanylate cyclase inhibitor (methylene blue) were tested, and none had a significant effect on the time to onset or duration of maximal dentate activation. A membrane-permeable analogue of cyclic guanosine monophosphate (cGMP), 8-bromo-cGMP, caused an increase in the time to onset and a decrease in the duration of maximal dentate activation. The number of neurons expressing NADPH diaphorase activity (a marker for nitric oxide synthase) was also examined after repeated elicitation of maximal dentate activation. After 18 seizures there was a significant, but transient, decrease in the number of hilar/subgranular neurons that were NADPH diaphorase-positive. The decrease was only seen at 1 h after the last seizure. There was no induction of NADPH diaphorase activity. These results are not consistent with the hypothesis that, in hippocampal-parahippocampal circuits in vivo, nitric oxide is released in response to neuronal activity and then acts to terminate the neuronal activity.