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.     

Lateral branchial cyst--case report

A case report of big lateral branchial cyst growing for 25 years is described. The diagnosis was based on ultrasonography with aspiration biopsy, computed tomography and histopathological findings. Successful surgical treatment was performed. Rarity of big size and long duration of the disease is emphasized.     

Intrinsic activity and comparative molecular dynamics of buspirone analogues at the 5-HT(1A) receptors

In CNS, the 5-hydroxytryptamine(1A) (5-HT(1A)) receptors exist in two different populations with different behavioural and physiological effects: (1) somatodendritic autoreceptors located pre-synaptically of 5-HT containing neurons and (2) receptors located post-synaptic to 5-HT containing neurons. Clinical studies have shown that 5-HT(1A) partial agonists have anxiolytic properties, while antagonists of pre-synaptical autoreceptors shorten the onset time of selective serotonin reuptake inhibitors (SSRIs). In the present study, the pre- and post-synaptic activity of structural analogues of buspirone was evaluated in animal models. A three dimensional model of the 5-HT(1A) receptor was used to study their interaction modes and helical displacements upon receptor binding. The predicted receptor-ligand interactions indicated similarities in the receptor binding modes for all buspirone analogues, and no clear relationship between receptor contact residues and activity at pre- and post-synaptic receptors. Comparative molecular dynamics (MD) simulations for 650ps indicated that pre-synaptic antagonistic behaviour is connected to large displacements of transmembrane helix (TMH) 7 upon binding, while pre-synaptic agonistic behaviour is connected to large displacements of TMH2 and small displacements of TMH7. Post-synaptic partial agonist behaviour is connected to large displacements of TMH4 and TMH5 upon binding, while post-synaptic antagonists only slightly displace these helices.     

Involvement of bradykinin, cytokines, sympathetic amines and prostaglandins in formalin-induced orofacial nociception in rats

1. This study characterises some of the mechanisms and mediators involved in the orofacial nociception triggered by injection of formalin into the upper lip of the rat, by assessing the influence of various treatments on behavioural nociceptive responses (duration of facial rubbing) elicited either by a low subthreshold (i.e. non-nociceptive; 0.63%) or a higher concentration of the algogen (2.5%). 2. The kininase II inhibitor captopril (5 mg kg(-1), s.c.) and prostaglandin(PG) E(2) (100 ng lip(-1)) potentiated both phases of the response to 0.63% formalin, whereas tumour necrosis factor (TNF alpha; 5 pg lip(-1)), interleukin(IL)-1 beta (0.5 pg lip(-1)), IL-6 (2 ng lip(-1)) and IL-8 (200 pg lip(-1)), or the indirectly acting sympathomimetic drug tyramine (200 microg lip(-1)), each augmented only the second phase of nociception. 3. Conversely, both phases of nociception induced by 2.5% formalin were inhibited by the bradykinin (BK) B(2) receptor antagonist HOE140 (5 microg lip(-1)) or the selective beta(1)-adrenoceptor antagonist atenolol (100 microg lip(-1)). However, the BK B(1) receptor antagonist des-Arg(9)-Leu(8)-BK (1 and 2 microg lip(-1)), antibody and/or antiserum against each of the cytokines, the adrenergic neurone blocker guanethidine (30 mg kg(-1) day(-1), s.c., for 3 days) and the cyclooxygenase(COX)-2 inhibitor celecoxib (50 and 200 microg lip(-1), s.c.; or 1 and 3 mg kg(-1), i.p.) reduced only the second phase of the response. The nonselective COX inhibitor indomethacin and the 5-lipoxygenase activating protein inhibitor MK886 did not change formalin-induced nociception. 4. Our results indicate that BK, TNF-alpha, IL-1 beta, IL-6, IL-8, sympathetic amines and PGs (but not leukotrienes) contribute significantly to formalin-induced orofacial nociception in the rat and the response seems to be more susceptible to inhibition by B(2) receptor antagonist and selective COX-2 inhibitor than by B(1) receptor antagonist or nonselective COX inhibitor.     

Complex cytogenetics in a case of probably work related MDS/AML

In the majority of cases of overt acute myeloid leukemia (AML), there is no knowledge about a preleukemic phase of myelodysplastic syndrome (MDS). A few recent case-control studies suggest an association between MDS and several occupations. We report a unique case of MDS/AML related to the patient’s work condition with numerous cytostatic agents. The karyotype revealed a spectrum of genetic rearrangements identified by conventional cytogenetics, fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY). We suggest that amplification of chromosomal material may play a greater role in leukemogenesis than has been recognized previously.     

Adjuvant therapy in pancreatic cancer: Phase I trial of radiation dose escalation with concurrent full-dose gemcitabine

PURPOSE: To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma. METHODS AND MATERIALS: The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC). RESULTS: The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins (p <0.0001); treatment for recurrent disease (p <0.0001); primary location in the head and neck or deep trunk (p <0.0001); age >64 years (p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma (p = 0.01); tumor size >10 cm (p = 0.02); postoperative radiation dose <64 Gy (p = 0.03); and high histologic grade (p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors. CONCLUSION: The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.