Temporomandibular joint injuries

The clinical and radiologic findings in 30 patients who sustained injuries to the temporomandibular joint (TMJ) were retrospectively analyzed. Imaging consisted of variable combinations of radiography, tomography, two-compartment arthrography, computed tomography, and magnetic resonance imaging and was performed 2 days to 24 months after injury. Indications for imaging included acquired and/or unstable occlusal disturbances, cephalalgia, facial pain, otalgia, TMJ pain, tinnitus, dizziness, hearing disturbance, masticatory dysfunction, and muscle atrophy. Radiologic findings included internal derangement of the TMJ meniscus, swelling of retrodiskal tissues, joint effusion, mandibular condyle and condylar neck fractures, osteochondritis dissecans, avascular necrosis, degenerative condylar remodeling, osteoarthritis, musculotendinous injuries, and atrophy of masticatory muscles. After imaging studies, seven patients underwent surgery, at which time imaging findings were confirmed; one patient underwent successful aspiration of a painful hemarthrosis. TMJ injuries may result in joint derangement, radiologically demonstrable joint degeneration, masticatory muscle dysfunction, pain, and progressive clinical disability.     

The predominance of Th17 lymphocytes and decreased number and function of Treg cells in preeclampsia

The aim of this study was to estimate the prevalence of CD3(+)CD4(+) T lymphocytes producing IL-17, IL-2, IFN-γ, and IL-4, plus CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells, in peripheral blood of patients with preeclampsia and healthy women in the third trimester of normal pregnancy. Another purpose was to assess the immunosuppressive activity of Treg cells from patients with preeclampsia compared with controls. Thirty-four preeclampsia patients and 27 healthy pregnant women were included. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells and CD3(+)CD4(+) T lymphocytes with intracellular expressions of cytokines were estimated using monoclonal antibodies and flow cytometry. In vitro functional assays were performed using a Treg Cell Isolation Kit and (3)H-thymidine incorporation assays. The percentage of CD3(+)CD4(+) T lymphocytes producing IL-17A was significantly higher in preeclampsia than in healthy, normotensive pregnant women in the third trimester (p<0.001). The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in the study group compared with controls (p<0.05). There was no change in the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes from preeclampsia patients without Treg cells and after addition of autologous Treg cells. In normal pregnancy, the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes was significantly higher without Treg cells compared with the response after addition of autologous Treg cells (p<0.05). The results suggest up-regulation of the Th17 immune response in preeclampsia. The decreased number and function of Treg cells may be responsible for activating the inflammatory response characteristic of this disorder. In preeclampsia, the predominance of Th17 immunity could act through modulating the Th1/Th2 immune balance.     

Synthesis and evaluation of in vivo activity of diphenylhydantoin basic derivatives

During the search for antiarrhythmic agents among amide derivatives of phenytoin, compound 7 3-ethyl-1-[2-hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl]-2,4-dioxo-5,5-diphenyl-imidazolidine was selected as it showed antiarrhythmic as well as antihypertensive activity. Treating this compound as a lead, new derivatives 8–19 were synthesised, differing in piperazine phenyl ring substitution (2-, 3-, 4-Cl, 2-CH₃O) as well as in hydantoin N₃ alkyl chain (ethyl, ethyl acetate or ethyl 2-propionate). The obtained compounds in form of hydrochlorides 7a–19a were examined for prophylactic antiarrhythmic and antihypertensive properties. Compounds containing ethyl 2-propionate moiety (17a, 18a) exhibited the highest antihypertensive properties. Water-soluble compounds, containing 2-methoxyphenylpiperazine group (11a, 19a), showed strong antiarrhythmic properties in adrenaline-induced arrhythmia; compound 9a 1-[3-(4-(3-chloro-phenyl)-piperazin-1-yl)- 2-hydroxy-propyl]- 3-ethyl-2,4-dioxo-5,5-diphenyl-imidazolidine hydrochloride exhibited the highest antiarrhythmic activity in barium chloride arrhythmia model.     

The Positive Impact of Vitamin D on Glucocorticoid-Dependent Skeletal Muscle Atrophy

(1) The study aimed to investigate whether vitamin D₃ supplementation would positively affect rats with glucocorticoids-induced muscle atrophy as measured by skeletal muscle mass in two experimental conditions: chronic dexamethasone (DEX) administration and a model of the chronic stress response. (2) The study lasted 28 consecutive days and was performed on 45 male Wistar rats randomly divided into six groups. These included two groups treated by abdominal injection of DEX at a dose of 2 mg/kg/day supplemented with vegetable oil (DEX PL; n = 7) or with vitamin D₃ 600 IU/kg/day (DEX SUP; n = 8), respectively, and a control group treated with an abdominal injection of saline (CON; n = 6). In addition, there were two groups of rats chronically stressed by cold water immersion (1 hour/day in a glass box with 1-cm-deep ice/water mixture; temperature ~4 °C), which were supplemented with vegetable oil as a placebo (STR PL; n = 9) or vitamin D₃ at 600 IU/kg/day (STR SUP; n = 9). The last group was of sham-stressed rats (SHM; n = 6). Blood, soleus, extensor digitorum longus, gastrocnemius, tibialis anterior, and quadriceps femoris muscles were collected and weighed. The heart, liver, spleen, and thymus were removed and weighed immediately after sacrifice. The plasma corticosterone (CORT) and vitamin D₃ metabolites were measured. (3) We found elevated CORT levels in both cold water-immersed groups; however, they did not alter body and muscle weight. Body weight and muscle loss occurred in groups with exogenously administered DEX, with the exception of the soleus muscle in rats supplemented with vitamin D₃. Decreased serum 25(OH)D₃ concentrations in DEX-treated rats were observed, and the cold water immersion did not affect vitamin D₃ levels. (4) Our results indicate that DEX-induced muscle loss was abolished in rats supplemented with vitamin D₃, especially in the soleus muscle.     

Prospective study of rotaviral infections in children hospitalized at the Clinic of Pediatric Infectious Diseases in Białystok in 2003

Rotavirus is the most common gastrointestinal pathogen in infants and young children. The aim of this study was to determine the role of rotavirus in acute diarrhea in children hospitalized in Pediatric Infectious Diseases Clinic in Bialystok. 658 children aged 0-7 years admitted to the ward: 466 children with gastroenteritis and another 192 without any diarrheic symptoms were tested for rotavirus infection by latex agglutination. Rotavirus was detected in 16.1% stool specimens collected from children with acute diarrhea. None of patients without diarrhea was positive for rotavirus on admission--2% of this patients acquired symptomatic rotavirus infection during hospitalization. This study delivers epidemiological data on rotavirus infection and shows the need of further study on etiology of viral gastroenteritis in children in our district.     

Nitric oxide and convulsions in 4-aminopyridine-treated mice

We studied whether N(G)-nitro-L-arginine (NNA), an inhibitor of nitric oxide (NO) synthase as well as L-arginine and molsidomine, two agents elevating NO, influenced convulsions caused by 4-aminopyridine, a K+ channel blocker in mice. NNA, in a dose known to decrease level of NO (40 mg x kg(-1)), enhanced the seizure susceptibility to intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) 4-aminopyridine. L-arginine (500 mg x kg(-1)) and molsidomine (20 mg x kg(-1)) alone did not influence 4-aminopyridine-induced seizure activity. Surprisingly, the proconvulsant effect of NNA upon clonic and tonic seizures was potentiated by molsidomine (20 mg x kg(-1)). No influence of L-arginine on the proconvulsant effect of NNA was found.Taking into account the proconvulsant effect of NNA, an involvement of NO-mediated events in the mechanism of convulsive activity of 4-aminopyridine might be postulated. However, the ineffectiveness of L-arginine and molsidomine to suppress the convulsive activity of 4-aminopyridine as well as a paradoxical potentiation of the proconvulsant effect of NNA by molsidomine seem to exclude the impact of NO pathway on 4-aminopyridine-induced convulsions in mice. Our data suggest that the proconvulsant effect of NNA in this seizure model is caused by other, not related to NO, mechanisms.     

Central nervous system activity of new pyrimidine-8-on[2,1-f]theophylline-9-alkylcarboxylic acids derivatives

The appropriate esters 1-3 were synthesized by the alkylation of unsubstituted pyrimidin-8-on[2,1-f]theophylline I with ethyl-chloroacetate, ethyl-acrylate and ethyl-4-bromobutyrate. The acids 4-6 were obtained by hydrolysis of the esters 1-3, and transformed into Na salts 4a-6a. Amidation of the ester 1 with 25% ammonia and hydroxylamine led to amide 7 and N-hydroxyamide 8. The bromination of 1 gave 7-bromo intermediate 9 transformed to the 7-amino derivatives via nucleophilic substitution with phenylpiperazine for compound 10 and morpholine for compound 11. In the reaction of 9, 10 and 11 with sodium alcoholate, the corresponding Na salts 12a-14a were obtained. The pharmacological properties of the compounds were tested in CNS activity screening. It was found that all of the investigated compounds produced significant sedative effects in behavioral tests except weak activity of pyrimido[2,1-f]theophylline-9-sodium acetate 4a. The potent activity of pyrimido[2,1-f]theophylline-9-sodium butyrate 6a, pyrimido[2,1-f]theophylline-9-acetamide-7,7-N-phenylpiperazine-pyrimido[2,1-f]theophylline-9-sodium acetate 13a, and 7-N-morpholine-pyrimido[2,1-f]theophylline-9-sodium acetate 14a was observed. They inhibited spontaneous locomotor activity, potentiated sedation and prolonged duration of sleeping time after thiopental sodium administration. All compounds had no effects in the test of analgesia and they showed weak anti-convulsant properties. The results of this investigation may suggest hypnotic, sedative and/or tranquillizing properties of the tested compounds.     

Using mammographic density to improve breast cancer screening outcomes

It is possible that the performance of mammographic screening would be improved if it is targeted at women at higher risk of breast cancer or who are more likely to have their cancer missed at screening, through more intensive screening or alternative screening modalities. We conducted a case-control study within a population-based Australian mammographic screening program (1,706 invasive breast cancers and 5,637 randomly selected controls). We used logistic regression to examine the effects of breast density, age, and hormone therapy use, all known to influence both breast cancer risk and the sensitivity of mammographic screening, on the risk of small (15 mm) screen-detected and interval breast cancers. The risk of small screen-detected cancers was not associated with density, but the risk of large screen-detected cancers was nearly 3-fold for the second quintile and approximately 4-fold for the four highest density categories (third and fourth quintiles and the two highest deciles) compared with the lowest quintile. The risk of interval cancers increased monotonically across the density categories [highest decile odds ratio (OR), 4.65; 95% confidence interval (95% CI), 2.96-7.31]. The risk of small and large screen-detected cancers, but not interval cancers, increased with age. After adjusting for age and density, hormone therapy use was associated with a moderately elevated risk of interval cancers (OR, 1.43; 95% CI, 1.12-1.81). The effectiveness of the screening program could be improved if density were to be used to identify women most likely to have poor screening outcomes. There would be little additional benefit in targeting screening based on age and hormone therapy use.     

Influence of DNA repair gene polymorphisms on prognosis in inoperable non-small cell lung cancer patients treated with radiotherapy and platinum-based chemotherapy

Polymorphisms in DNA repair genes may modulate not only an individual DNA repair capacity, DNA damage levels and cancer risk but also clinical outcome after DNA damage-inducing anticancer therapy. In this study, we analyzed the association between the XPA -4G>A, XPD Asp312Asn, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC2 -4234G>C, XRCC3 -4541A>G and Thr241Met polymorphisms and prognosis in 250 inoperable non-small cell lung cancer (NSCLC) patients treated with radiotherapy and platinum-based chemotherapy. In univariate model, the XPA-4A and XRCC1 399Gln alleles alone and in combination influenced survival only in stage III group. In multivariate analysis, the XPA-4 GA/AA was associated with poor survival (HR 1.55, p = 0.011 overall and HR 1.72, p = 0.008 in stage III). In chemoradiotherapy group, the XPA-4A carriers were at increased risk of death and progression (HR 1.73, p = 0.013 and HR 1.65, p = 0.016, respectively), especially in stage III (p = 0.008). Moreover, individuals with ≥ 2 XPA/XRCC1 adverse alleles showed a higher risk of death (HR 1.46, p = 0.036 overall; HR 1.85, p = 0.004 in stage III and HR 1.71, p = 0.022 in chemoradiotherapy group) and progression (HR 1.75, p = 0.011 overall and HR 1.93, p = 0.005 in stage III). The XPA-4 GA/AA genotype individually and together with the XRCC1 399Gln was an independent unfavorable prognostic factor in our study. Thus, our findings indicate a prognostic potential of the XPA-4G>A in unresected NSCLC treated with radiotherapy and chemoradiotherapy. The results require validation in an independent population.