Long-term potentiation protects rat hippocampal slices from the effects of acute hypoxia.

We have previously shown that long-term potentiation (LTP) decreases the sensitivity of glutamate receptors in the rat hippocampal CA1 region to exogenously applied glutamate agonists. Since the pathophysiology of hypoxia/ischemia involves increased concentration of endogenous glutamate, we tested the hypothesis that LTP could reduce the effects of hypoxia in the hippocampal slice. The effects of LTP on hypoxia were measured by the changes in population spike potentials (PS) or field excitatory post-synaptic potentials (fepsps). Hypoxia was induced by perfusing the slice with (i) artificial CSF which had been pre-gassed with 95%N2/5% CO2; (ii) artificial CSF which had not been pre-gassed with 95% O2/5% CO2; or (iii) an oxygen-glucose deprived (OGD) medium which was similar to (ii) and in which the glucose had been replaced with sucrose. Exposure of a slice to a hypoxic medium for 1.5-3.0 min led to a decrease in the PS or fepsps; the potentials recovered to control levels within 3-5 min. Repeat exposure, 45 min later, of the same slice to the same hypoxic medium for the same duration as the first exposure caused a reduction in the potentials again; there were no significant differences between the degree of reduction caused by the first or second exposure for all three types of hypoxic media (P>0.05; paired t-test). In some of the slices, two episodes of LTP were induced 25 and 35 min after the first hypoxic exposure; this caused inhibition of reduction in potentials caused by the second hypoxic insult which was given at 45 min after the first; the differences in reduction in potentials were highly significant for all the hypoxic media used (P<0.01; paired t-test). The neuroprotective effects of LTP were not prevented by cyclothiazide or inhibitors of NO synthetase compounds that have been shown to be effective in blocking the effects of LTP on the actions of exogenously applied AMPA and NMDA, respectively. The neuroprotective effects of LTP were similar to those of propentofylline, a known neuroprotective compound. We conclude that LTP causes an appreciable protection of hippocampal slices to various models of acute hypoxia. This phenomenon does not appear to involve desensitisation of AMPA receptors or mediation by NO, but may account for the recognised inverse relationship between educational attainment and the development of dementia.     

Oxidative stress and male IGF-1, gonadotropin and related hormones in diabetic patients.

Elevation of glucose concentration in diabetes may induce generation of oxygen free radicals such as superoxide (O2*-) and hydroxyl (*OH). The aim of the present study was to investigate the effect of the oxidative stress on the activities of blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and aldose reductase, the levels of reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances; TBARS) and plasma levels of insulin-like growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in type 2 (non-insulin-dependent diabetes) patients and in healthy controls. Blood SOD, CAT, GSH-Px and GSSG-R were lower in type 2 diabetic patients compared with the the control group. Blood aldose reductase activity was elevated in patients with type 2 diabetes compared with the control group. GSH was decreased while TBARS concentration was increased in red blood cells (RBC) and leukocytes from the patients with type 2 diabetes mellitus in comparison to the control group. The mean values of plasma LH, FSH and testosterone were decreased, whereas the mean plasma IGF-1 concentration was increased in type 2 diabetes compared with controls. These findings support the hypothesis that hyperglycemia enhances the activity of the polyol pathway and impairs the antioxidant status, particularly glutathione redox cycle, resulting in poorer defense against oxidative stress. In addition, decreased circulating testosterone and gonadotropin levels may reflect the oxidative stress exerted by diabetes.     

Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge (Euphorbiaceae)

The feeding of lactating goats on usual green fodder, contaminated with Euphorbia helioscopia or E. nubica, results in poisoning of the dams as well as their suckling kids. General signs of toxicity were emaciation, depression, shedding of body hair, arching of back, and possible death. Post-mortem changes of dams and dead suckling kids included congestion and hemorrhage in cardiac muscle, lung, liver, and kidneys. Blood analyses of goats exposed to these contaminants showed an increased level of serum alanine amino transferase compared to control samples, indicating cellular destruction in the liver. The latter was confirmed by histopathological changes in the organ which include severe congestion, necrosis, and degenerative changes. The goats also suffered from deterioration of renal function as indicated by increased blood urea nitrogen and creatinine levels. In histopathologic inspections of kidney, severe congestion, hemorrhage in the cortex and medulla, as well as necrosis of epithelial cells of kidney tubules were noticed. Considerable degenerative changes were also observed in heart and lung. The pathophysiological appearances indicate that by feeding on the Euphorbia species mentioned above, the goats are poisoned in a way similar to the case of E. peplus reported previously. Such intoxication most likely is due to irritant and hyperplasiogenic diterpene ester (DTE) toxins, usually present in the aerial parts of Euphorbia species and well known as tumor promoters in mouse skin. After ingestion of the toxic plant parts by the goats, the DTE toxins might be metabolized and thereby partially detoxified. Yet, at least in part, they may show up in the milk of the goats, as indicated by severe poisoning of their suckling kids. As discussed previously in lactating goats fed on fodder contaminated with E. peplus, tumor promoters of the DTE type may enter the human food chain via this source of milk. Such milk may be considered a valuable etiologic model for the investigation of economic, ecologic, and public health problems raised by human diet polluted with tumor promoters, i.e., conditional (non-genotoxic) cancerogens. Received: 25 July 2000 / Accepted: 18 September 2000     

Cytochrome 4Z1 Expression Is Correlated with Poor Prognosis in Patients with Cervical Cancer

Background: cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 expression in cervical cancers. Methods: CYP4Z1 expression was immunohistochemically assessed in 100 cases of cervical cancers along with ten normal cervix tissues, and the enzyme’s relationship to several clinicopathological features and survival was explored. Results: CYP4Z1 was strongly expressed in 55% of cervical cancer patients. Normal cervix samples were negative for CYP4Z1 expression. Importantly, this expression was significantly found in patients with the late stage of the disease, lymph node metastasis, and high tumour invasion (p < 0.05). Interestingly, CYP4Z1 expression was significantly correlated with shorter survival times of cervical cancer patients. Univariate analysis showed that CYP4Z1 expression, tumour stage, lymph node metastasis, and tumour invasion were significantly correlated with patient survival (p < 0.05). The multivariate analysis revealed that only CYP4Z1 expression and tumour stage were significantly correlated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is associated with cervical cancer patients’ survival and may serve as an independent predictor of poor prognosis in cervical cancer patients.     

School nurse knowledge and perceptions of recurrent abdominal pain: opportunity for therapeutic alliance?

Recurrent abdominal pain of childhood affects up to 15% of school-age children, who face significant psychosocial consequences, including school absence. Because assessment of recurrent abdominal pain is frequently made at the school nurse level, a questionnaire was sent to 425 school nurses to evaluate perceptions about recurrent abdominal pain. Among the responses, 47.1% believed children were taking or seeking attention; 3.6% considered it a serious disease, 77.9% stated that affected children should see a physician, 51.5% believed they should relax, and 25.0% believed they needed medicine. Results indicated that school nurses were unclear on epidemiologic and etiologic features of recurrent abdominal pain and had negative views that may inadvertently contribute to the anxiety felt by affected children. Education of school nurses and communication from physicians may advance strategies designed to reduce the fiscal and social costs associated with this common childhood condition.     

Impetigo herpetiformis

Impetigo herpetiformis is a rare pustular disorder that occurs primarily in pregnancy and is often associated with hypocalcemia. The onset commonly presents in the last trimester of pregnancy; the condition may persist until delivery and it rarely continues in the postpartum period. There is an increase in morbidity and mortality for the mother and the fetus. As a result, immediate diagnosis and treatment is crucial. The purpose of this article is to delineate the clinical picture of this disease, its treatment, and the effect on the mother and the fetus.     

Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomised trials

Background  

Hormone replacement therapy (HRT) is often seen as the treatment of choice for preventing fractures in women. We undertook a recent meta-analysis of randomised trials which suggested that HRT reduced non-vertebral fractures by 30%. In this analysis we extend that analysis to vertebral fractures.     

Impact of mycophenolate mofetil on recurrent rejection in kidney transplant patients

PURPOSE: Mycophenolate mofetil (MMF) has emerged as a valuable adjunctive agent in renal transplantation. However, due to intolerable adverse effects associated with MMF use in our transplant population, we have used MMF selectively in patients at high risk for recurrent graft rejection, since these patients are known to be at risk for poor long-term graft outcomes. The purpose of this study was to assess the efficacy of MMF in preventing the recurrence of acute rejection following an initial rejection episode in kidney transplant patients in the first year following transplantation. METHODS: Forty-four kidney transplant recipients were given MMF prospectively following treatment of their initial rejection episode to prevent recurrent rejection. MMF 1-2 g/d was given. Doses were adjusted based on tolerance; MMF therapy was to be continued for at least 6 months. The control group consisted of 124 consecutive kidney transplant recipients who had received standard anti-rejection therapy without the addition of MMF. Maintenance immunosuppression consisted predominantly of cyclosporine, prednisone+/-azathioprine. Anti-rejection therapy for both groups consisted of either corticosteroids (methylprednisolone 500 mg i.v. for 3 d or oral prednisone 2 mg/kg/d with rapid taper over 3 wk), OKT3 5 mg/d for 10 d or ATG 15 mg/kg/d for 10 d. All rejection episodes were confirmed by biopsy. RESULTS: The majority of rejection episodes were characterized histologically as mild or moderate. Most patients (76%) received corticosteroids for treatment of their first rejection episode. There was a 68% reduction in the incidence of recurrent rejection episodes within the first year of transplant in patients receiving MMF; only 14% of recipients receiving MMF developed recurrent rejection compared to 44% of patients in the control group (p<0.05). Approximately 50% of patients developed MMF-associated adverse effects (leukopenia, GI toxicity). Only 52% of patients remained on MMF at 6 months. One-yr graft survival was 86% in the MMF group and 89% in the control group (p>0.05). One-year patient survival was 93 and 100%, respectively (p>0.05). CONCLUSIONS: The addition of MMF to maintenance therapy for patients experiencing acute renal allograft rejection may prevent recurrent rejection episodes in the subsequent follow-up year.