The antidepressant effect of running is associated with increased hippocampal cell proliferation

A common trait of antidepressant drugs, electroconvulsive treatment and physical exercise is that they relieve depression and up-regulate neurotrophic factors as well as cell proliferation and neurogenesis in the hippocampus. In order to identify possible biological underpinnings of depression and the antidepressant effect of running, we analysed cell proliferation, the level of the neurotrophic factor BDNF in hippocampus and dynorphin in striatum/accumbens in 'depressed' Flinders Sensitive Line rats (FSL) and Flinders Resistant Line (FRL) rats with and without access to running-wheels. The FRL strain exhibited a higher daily running activity than the FSL strain. Wheel-running had an antidepressant effect in the 'depressed' FSL rats, as indicated by the forced swim test. In the hippocampus, cell proliferation was lower in the 'depressed' rats compared to the control FRL rats but there was no difference in BDNF or dynorphin levels in striatum/accumbens. After 5 wk of running, cell proliferation increased in FSL but not in FRL rats. BDNF and dynorphin mRNA levels were increased in FRL but not to the same extent in the in FSL rats; thus, increased BDNF and dynorphin levels were correlated to the running activity but not to the antidepressant effect of running. The only parameter that was associated to basal level of 'depression' and to the antidepressant effect was cell proliferation in the hippocampus. Thus, suppression of cell proliferation in the hippocampus could constitute one of the mechanisms that underlie depression, and physical activity might be an efficient antidepressant.     

Exposure to PCBs and p,p'-DDE and human sperm chromatin integrity

Persistent organochlorine pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (p,p'-DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), are stable lipophilic compounds widely found in the environment and in the general population. They can enter the food chain, and their negative impact on male reproduction is currently under active scrutiny. To explore the hypothesis that environmental exposure to these compounds is associated with altered sperm chromatin structure integrity in human sperm, we conducted a study of 176 Swedish fishermen (with low and high consumption of fatty fish, a very important exposure source of POPs). We determined serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and p,p'-DDE, and we used the sperm chromatin structure assay (SCSA) to assess sperm DNA/chromatin integrity. When CB-153 serum levels (individual dose range, 39-1,460 ng/g lipid) were categorized into equally sized quintiles, we found an association with the DNA fragmentation index (%DFI). A significantly lower %DFI was found in the lowest CB-153 quintile (< 113 ng/g lipid) compared with the other quintiles; there was a similar tendency, although not statistically significant, between %DFI and p,p'-DDE. These results suggest that POP exposure may have a slight negative impact on human sperm chromatin integrity.     

The treatment of advanced chronic lower limb ischaemia with marrow stem cell autotransplantation

INTRODUCTION: Conventional methods of critical leg ischaemia treatment are of limited efficacy. Amputation, as an ultimate solution, is not so rare. The results of marrow stem cell therapy as a potential novel approach to peripheral artery disease management were presented in 2002 by Tateishi-Yuyamy. AIM: To assess efficacy and safety of critical lower limb ischaemia treatment with marrow stem cell autotransplantation. METHODS: Ten patients suffering from chronic leg ischaemia in Fontaine IV stadium were involved in the study. They did not require emergency amputation and had previously been unsuccessfully treated with conventional therapy. Autologic marrow stem cells were condensated by a separator from bone marrow samples taken from the iliac crest. The cells were delivered intramuscularly by repeated injections into the pedal and tibial regions. The number of CD34 and AC133 positive mononuclear cells in each sample was evaluated by flow cytometry. After two weeks and one, two, three and twelve months the following parameters were measured: Laser Doppler Flux (LDF), percutaneous oxygen partial pressure, ankle-brachial index (ABI), visual analgesic scale (VAS), analgesic therapy requirement and ulceration area. Also, lower leg angiography and scintigraphy were performed. RESULTS: An improvement of the peripheral blood flow assessed by Laser Doppler Flux and percutaneous oxygen partial pressure was found. Pain severity decreased in the majority of patients. Amputation was required in three patients in whom the therapy failed. No side effects of the therapy were observed. The clinical effect of the treatment did not correlate with the amount of cells injected. CONCLUSION: Marrow stem cell autotransplantation into the ischaemic lower limb seems to be a potentially effective method of peripheral perfusion enhancement. Further studies are needed to clarify the underlying mechanisms of such improvement.     

Quantitative assessment of mRNA TGF-beta1 in liver tissue in connection with serum mean daily level of TGF-1 in chronic hepatitis B patient

Monitoring of fibrosis process with the use of histopathologic studies on liver's bioptates is limited, so it is attempted to find reliable, obtained with less invasive methods, sensitive and reflecting fibrosis dynamics markers of this process. The aim of the study was simultaneously to assess liver's expression as well as circadian and mean daily TGF-betal concentration in serum of patients with chronic hepatitis type B in comparison to control group. Studies were performed on 50 patients (9 women, 41 men) aged 45.9 +/- 2.3 years with chronic hepatitis type B. Control group consisted of 20 patients (mean age 38.6 +/- 3.7 years), in which so called minimal changes without fibrosis were observed in histophatologic bioptate of liver. Blood for studies was collected every 4 houres during the day. Serum concentration of TGF-betal was assessed with the use of ELISA method, and expression of mRNA TGF-betal in liver with QRT-PCR method. No significant difference between circadian as well as mean daily serum TGF-betal concentration beetwen control group and the group with chronic hepatitis type B was shown. Increased expression of mRNA, TGF-betal in bioptate of liver of patients with chronic hepatitis type B in comparison to control group was noted. In "minimal changes" control group presence of significant positive correlation between expression of mRNA TGF-beta1 in liver and concentration of this cytokine in serum was shown, in the group of patients with chronic hepatitis B this connection was not noted.     

Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence: relation to anxiety-like and depressive-like behavior

OBJECTIVE: Recently, animal models have been developed that demonstrate that adolescent nicotine exposure produces neurobehavioral changes which persist into adulthood. This study further examined the impact of adolescent nicotine exposure on anxiety-like and depressive-like behavior, as well as on levels of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) in this model. METHODS: Male adolescent rats (35-40 days old) were administered nicotine using Nicoderm CQ patches (Smith-Kline Beecham). Behavior in the elevated plus maze (EPM) and forced swim test (FST) was assessed 2-3 weeks after exposure ended. Brain levels of CRF and NPY were then assessed 5-6 weeks after behavioral tests were completed. In addition, blood and brain levels of nicotine resulting from nicotine treatment were examined. RESULTS: After 5 days of exposure to 5 mg/kg/day nicotine, blood levels of nicotine averaged 66+/-5 ng/ml and brain nicotine levels averaged 52+/-4 ng/g. Rats exposed to nicotine displayed an anxiety-like profile in the EPM (i.e., decreased time spent in the open arms) and an antidepressant-like profile in the FST (i.e., less time spent immobile). Rats exposed to nicotine also had increased hypothalamic and frontal cortical CRF, increased hypothalamic and hippocampal NPY, and a decreased ratio of NPY to CRF in the amygdala. CONCLUSIONS: This study demonstrates that adolescent nicotine exposure produces lasting increases in anxiety-like behavior and may reduce depressive-like behavior. These behavioral changes also occurred in concert with alterations in CRF and NPY systems. Thus, lasting neurobehavioral changes associated with adolescent nicotine exposure may be related to allostatic changes in stress peptide systems.     

Sensitization to the storage mite Tyrophagus putrescentiae in urban population of Upper Silesia (Poland)

Exposure to indoor allergens, especially dust mites has been recognized as a risk factor for sensitization and allergy symptoms that in extreme conditions could develop into asthma. To determine specific antigens responsible for allergy in patients positive for mite allergy skin tests whole protein extracts from the cultured mite species Tyrophagus putrescentiae [TP], and from their excrements were obtained. The proteins were fractionated by SDS PAGE and identified by Western blot. The patient antibodies against particular antigens were identified in serum IgE fraction using anti-human anti-IgE monoclonal antibody. Western blot analysis revealed differences in reactivity of sera from patients positive for standard mite allergy skin tests with fractionated mite antigens. A total of 17 of 30 sera (56.7%) from patients positive to skin tests showed specific cross reactivity with antigens isolated from extracts of TP. The results revealed that 12 out of 30 tested sera (40.0%) reacted specifically with new antigens identified as protein fractions of extracts from excrements of TP. When assessing mite allergen reaction using mixture of mite proteins the results of the test are not satisfactory for determining the antigen causing patient allergy. The results obtained from studies reported here indicate significant discrepancy between the so called standard allergy skin test and what the patient is actually sensitive to. Also, a new class of immunizing protein of about 25 kDa has been identified in excrements from TP reacting with IgE from patients showing allergy to other mite extracts. A total of 4 of 30 sera (approx. 13.3%) from patients positive to skin tests showed specific cross reactivity with antigens isolated from mite excrements rather than from mite whole extracts.     

Oxford Phase 3 Unicompartmental Knee Arthroplasty (UKA): Clinical and radiological results of minimum follow-up of 2 years

Background. Since the introduction minimally invasive techniques, interest in unicompartmental knee arthroplasty (UKA) has rapidly increased. This minimally invasive approach preserves the anatomy of the knee with less damage to extensor mechanisms, less morbidity, and quicker post-operative recovery. The purpose of our study was to evaluate this new treatment option for anteromedial osteoarthritis, both clinically and radiographically, and to identify any possible drawbacks. Material and methods. Between January 1999 and August 2003 88 consecutive Oxford Phase 3 UKAs were implanted by a single surgeon. All patients with a minimal follow-up (FU) period of 2 years were pre- and post- operatively clinically evaluated by the American Knee Society (AKS) Score and radiographically according to the Oxford Centre criteria, including fluoroscopy. Results. Twenty-eight patients with 30 prostheses with a minimal follow-up period 2 years (2.54 +/- 0.48 yrs) were included in this study. The AKS Knee, Function and Pain Score improved significantly at 2-year FU compared to the preoperative score, the preoperative varus deformity was corrected into alignment in all cases. Conclusions. Clinical and radiographical results of the Oxford Phase 3 prosthesis using a minimally invasive surgical technique confirmed previous good results achieved by the standard technique. Evaluation of our patients at a minimum FU of 2 years revealed a significant improvement of AKS scores. Postoperatively knee joint deformity was corrected into a physiological valgus alignment. Patient satisfaction is high, and the prosthesis provides good outcome for patients with anteromedial osteoarthritis when strict indication criteria are considered.