Macrophages hold the key to cancer's inner sanctum.

All malignancies contain tumor-associated macrophages (TAMs) that facilitate cancer growth by secreting chemicals to elicit angiogenesis and shield the cancer from the immune system. The abundance of TAMs is a reflection of invasiveness and metastatic potential. TAMs will actively ingest ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles following intravenous administration and will store them as large lysosomal aggregates which can be imaged with MRI and ultrasound and visualized or quantitated in tissue biopsies. Since the USPIO also enhances regional lymph nodes, it is possible to include this information for more accurate cancer staging. The USPIO aggregates surprisingly also serve as heat sinks and can enhance hyperthermic regimens with focal laser, focused microwaves, or high-intensity focused ultrasound (HIFU). The hyperthermic intervention can be chosen based upon accessibility for the selected energy source. By sustaining an intratumoral elevation of temperature for an effective period of time, ablation of a small or large fraction of the TAMs and cancer cells can be achieved. Thus, for aggressive cancer, USPIO is a theragnostic agent. Following USPIO-enhanced hyperthermia, the resulting debris will slowly reach the regional lymphatics and immune recognition may result. An effective vaccine or adjuvant could be injected peritumorally to improve immunorecognition of that patient's cancer. The field of immunotherapy is being intensely explored at present. Using the theragnostic properties of USPIOs that are accumulated in the TAMs may prove useful in further attempts to make immunotherapy successful. This intervention could be utilized at any stage of cancer therapy. Should immunological recognition occur, an abscopal response may be achieved for that patient and for his/her cancer. This would truly be personalized cancer therapy.

Subjective and objective parameters in the evaluation of radiofrequency ablation of the inferior turbinate do not correlate: A pilot study.

Inferior turbinate hypertrophy is a common cause of nasal obstruction. We conducted a prospective study to correlate subjective and objective parameters in assessing the effectiveness of radiofrequency ablation (RFA). Our initial study population was made up of 10 patients who presented with nasal obstruction; 1 patient was lost to follow-up, leaving us with 7 women and 2 men, aged 26 to 65 years (mean: 37.9 ± 12.8), and 16 turbinates (7 bilateral, 1 right, and 1 left). Visual analogue scale (VAS) scores, Nasal Obstruction and Symptom Evaluation (NOSE) questionnaire scores, rhinomanometry results, and CT- and MRI-based volumetry were obtained before RFA and 6 months afterward. For the subjective parameters, the mean pre- and postoperative VAS scores for the 16 turbinates were 6.6 ± 1.6 and 2.8 ± 2.0 (p < 0.001), respectively, and the mean pre- and postoperative NOSE scores in the 9 patients were 15.3 ± 3.1 and 5.8 ± 5.4 (p = 0.003). For the objective parameters, the mean pre- and postoperative rhinomanometry values at 150 Pa were 241.0 ± 141.3 and 265.4 ± 157.3 ml/sec (p = 0.403), and the mean pre- and postoperative volumetry values were 5.3 ± 2.5 and 5.0 ± 2.1 cm(3) (p = 0.551). Note that only the differences in the subjective parameters reached statistical significance. RFA of the inferior turbinates as a treatment for nasal obstruction is safe and easy. However, our study found a discrepancy between the subjective and objective outcomes parameters, as the former showed highly significant improvement and the latter showed only a slight improvement that did not reach statistical significance.

Kratom alkaloids and O-desmethyltramadol in urine of a "Krypton" herbal mixture consumer.

AIM: A drug and alcohol withdrawal rehabilitation centre requested an analysis for "Krypton" in urine of a former opiate-addictive woman. She showed an altered clinical picture and behaviour with miosis, itchiness, agitation, and moderate euphoria after 3 months of until than successful treatment. Literature search revealed that "Krypton" is said to contain "Kratom" (leaves of Mitragyna speciosa), but could also contain O-desmethyltramadol (European Monitoring Centre for Drugs and Drug Addiction thematic paper "Spice"). METHODS: Immunological drug screenings were done with test strips (nal von minden, Regensburg, Germany) and with cloned enzyme donor immunoassay (Microgenics, Passau, Germany). "Kratom" alkaloids and tramadol (metabolites) were analyzed by LC-MS/MS (ThermoFisher Scientific Quantum Ultra Triple Quadrupole mass spectrometer). RESULTS: Immunoassays were negative for amphetamines, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, ethylglucuronide, methadone (metabolite), opiates, oxycodone, and THC-COOH, and test strips were negative for tramadol and its metabolites (cut-off 10 mg/L for O-desmethyltramadol). LC-MS/MS detected the "Kratom" alkaloids mitragynine, speciociliatine, speciogynine, mitraciliatine, and paynantheine and approximately 9mg/L O-desmethyltramadol, but no tramadol and N-desmethyltramadol. DISCUSSION: The detection of M. speciosa alkaloids is a proof of "Kratom" abuse. Confronted with the analysis data, the patient admitted to have consumed 3-4 infusions of "Krypton". The origin of the O-desmethyltramadol is unclear. Tramadol abuse is unlikely since tramadol and N-desmethyltramadol (physiologically occurring in urine after tramadol intake) were not detectable. Consumption of a "Krypton" product spiked with O-desmethyltramadol could explain our findings and the patient's clinical picture. This would be in agreement with a most recent report about spiking apparently natural herbal mixtures with the synthetic opioid O-desmethyltramadol. CONCLUSION: Analysis of "Kratom" abuse should not be restricted to M. speciosa alkaloids, but should also consider synthetic drugs which could be added to the herbal mixtures. Mass spectrometry based drug screenings will gain importance to keep pace with the dynamic drug market.

Influence of topical antifungal drugs on ciliary beat frequency of human nasal mucosa: an in vitro study.

OBJECTIVES/HYPOTHESIS: Topical antifungal treatment is a subject of discussion in the treatment of chronic rhinosinusitis. The aim of this research was to study the effects of antifungal drugs on ciliary beat frequency (CBF) of human nasal mucosa under in vitro conditions. STUDY DESIGN: Case series of in vitro experiments and in vitro study of cultured ciliated cells of human nasal mucosa. METHODS: Human nasal mucosa was acquired during routine endoscopic sinus surgery. Cells were cultivated on object slides and exposed to different antifungal drugs in a newly developed test system. This system allowed continuous and reproducible exposure to different drugs at constant temperature, pH value, and osmolarity. The drugs were amphotericin B in two different concentrations and itraconazole. RESULTS: Rinsing with higher concentrations of amphotericin B led to an immediate decrease of CBF, with a total stop after 15 minutes. A different result was seen in the group with lower concentrations; CBF decreased again quickly after rinsing with the test drug, but all of them recovered after rinsing with neutral solution. When using itraconazole a decline in CBF was observed again; one half of the samples returned to activity. CONCLUSIONS: Our in vitro results demonstrate a dose-dependent effect of the antifungal drugs amphotericin B and itraconazole on ciliary beat frequency of human nose epithelium.

Minocycline recovers MTT-formazan exocytosis impaired by amyloid beta peptide.

Minocycline, a tetracycline antibiotic, has been reported to exert beneficial effects in models of Alzheimer's disease (AD). To characterize the mechanisms underlying the putative minocycline-related neuroprotection, we studied its effect in an in vitro model of AD. Primary hippocampal cultures were treated with ß-amyloid peptide (Aß) and cell viability was assessed by standard MTT-assay. Incubation with 10 µM Aß for 24 h significantly inhibits cellular MTT-reduction without inducing morphological signs of enhanced cell death or increase in release of lactate dehydrogenase. This indicates that cell viability was not affected. The inhibition of MTT-reduction by Aß was due to an acceleration of MTT-formazan exocytosis. Intriguingly, the Aß-triggered increase in MTT-formazan exocytosis was abolished by co-treatment with minocycline. In vehicle-treated cells minocycline had no effect on formazan exocytosis. This hitherto unrecognized property of minocycline has to be noticed in the elucidation of the underlying mechanism of this promising neuroprotectant.

Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer.

PURPOSE: Women with breast cancer that initially involves local lymph nodes have a higher risk for local recurrence or developing metastases. Recent data suggest that germline polymorphism is a significant, previously unrecognized factor in breast cancer progression and metastasis. We assessed the influence of 16 selected common germline polymorphisms in disease-free survival and overall survival among 216 women diagnosed with lymph node-positive breast cancer. RESULTS: The rare allele of FAS 1377G>A was significantly associated with prolonged disease-free survival (P = 0.012, risk ratio of recurrence (RR) = 0.557, 95% confidence interval (CI) = 0.353-0.878) in univariate analysis. After adjusting for known breast cancer prognostic factors the association remained significant (P = 0.050, RR = 0.500, CI = 0.309-0.809). In overall survival analysis we found a significant association of the FAS 1377G>A (P = 0.040, RR = 0.451, CI = 0.496-1.188) and IL10 592C>A polymorphisms (P = 0.020, RR = 1.707, CI = 1.087-2.680) in the univariate Cox regression. The effect remained statistically significant in the multivariate analysis for the IL10 592C>A polymorphism (P = 0.013, RR 1.841, CI 1.140-2.973). No association was found for MTHFR 677C>T, VEGF 936C>T, CCND1 870G>A, TGFB1 29T>C, FASLG 844C>T, FAS 670A>G, GPB3 825C>T, ITGA2 807C>T, ITGA2 1648G>A, ITGB3 176T>C, MMP1 -1607 1G/2G, MMP3 5A/6A, PTGS2 8473T>C, IL10 592C>A and SULT1A1 638G>A polymorphisms and disease-free survival or overall survival. CONCLUSIONS: Our data suggest that the FAS 1377G>A and IL10 592C>A polymorphisms could modify disease-free and overall survival in women with lymph node-positive breast cancer.

Urocortin 1 administered into the hypothalamic supraoptic nucleus affects open-field behaviour in rats.

The presence of both Urocortin 1 (Ucn1) and corticotropin-releasing factor 2 receptors (CRF(2)R) in the hypothalamic supraoptic nucleus (SON) suggests that endogenous Ucn1 released within this brain area acts as a local signal that might be involved in the regulation of not only endocrine but also behavioural stress responses. To test this hypothesis, we monitored the effects induced by the administration of a range of doses of synthetic Ucn1 (0.001-1.0 microg) bilaterally into the SON of rats in the open field test (OFT). Ucn1 administration produced an inverted U-shaped dose-response curve on OFT behaviour, in particular the dose of 0.01 microg of Ucn1 significantly increased the number of rearing and grooming episodes without affecting locomotion. In addition, this dosage augmented also the latency to visit the centre of the open field. Pre-treatment with the CRF(2)R antagonist, astressin-2B (0.1 microg) normalized Ucn1 treatment-induced effects. These results suggest that Ucn1 released within the SON area interacts with CRF(2)R to control the state of arousal.

The pharmacokinetics of the lymphotropic nanoparticle MRI contrast agent ferumoxtran-10.

Ferumoxtran-10 is an ultrasmall superparamagnetic biodegradable iron oxide which serves as a MRI contrast agent in the differentiation of metastatic and non-metastatic lymph nodes in primary malignancies and imaging of phagocyte-associated disease processes. Ferumoxtran-10 is supplied as a lyophilized powder containing 210 mg of iron, 631 mg of dextran, and 27 mg of sodium citrate. The iron oxide core determines the magnetic properties of ferumoxtran-10, primarily its effects on the MR relaxation times, T1, T2, and T2*. Attachment of dextran prolongs the circulatory time of the nanoparticles. The intended human dose of ferumoxtran-10 is 2.6 mg Fe/kg. Reconstituted and diluted with physiological saline it is administered intravenously by means of a slow drip infusion. After initial vascular distribution of the particles, they are slowly phagocytosed by the reticuloendothelial system cells of the spleen, lymph nodes, bone marrow, and liver. When ferumoxtran-10 is present in phagocytic cells the iron oxide causes local magnetic field inhomogeneities which lead to increases in proton relaxation rates, resulting in signal loss on mid-T1/T2 or heavily T2-weighted MR images. Stored in lysosomes the particles are ultimately degraded: the iron enters the normal body iron metabolism cycle and dextran is eliminated mainly via the kidney.

Impairment of mitochondrial function by minocycline.

There is an ongoing debate on the presence of beneficial effects of minocycline (MC), a tetracycline-like antibiotic, on the preservation of mitochondrial functions under conditions promoting mitochondria-mediated apoptosis. Here, we present a multiparameter study on the effects of MC on isolated rat liver mitochondria (RLM) suspended either in a KCl-based or in a sucrose-based medium. We found that the incubation medium used strongly affects the response of RLM to MC. In KCl-based medium, but not in sucrose-based medium, MC triggered mitochondrial swelling and cytochrome c release. MC-dependent swelling was associated with mitochondrial depolarization and a decrease in state 3 as well as uncoupled respiration. Swelling of RLM in KCl-based medium indicates that MC permeabilizes the inner mitochondrial membrane (IMM) to K(+) and Cl(-). This view is supported by our findings that MC-induced swelling in the KCl-based medium was partly suppressed by N,N'-dicyclohexylcarbodiimide (an inhibitor of IMM-linked K(+)-transport) and tributyltin (an inhibitor of the inner membrane anion channel) and that swelling was less pronounced when RLM were suspended in choline chloride-based medium. In addition, we observed a rapid MC-induced depletion of endogenous Mg(2+) from RLM, an event that is known to activate ion-conducting pathways within the IMM. Moreover, MC abolished the Ca(2+) retention capacity of RLM irrespective of the incubation medium used, most likely by triggering permeability transition. In summary, we found that MC at low micromolar concentrations impairs several energy-dependent functions of mitochondria in vitro.

Inhibitory modulation of the mitochondrial permeability transition by minocycline.

The semi-synthetic tetracycline derivative minocycline exerts neuroprotective properties in various animal models of neurodegenerative disorders. Although anti-inflammatory and anti-apoptotic effects are reported to contribute to the neuroprotective action, the exact molecular mechanisms underlying the beneficial properties of minocycline remain to be clarified. We analyzed the effects of minocycline in a cell culture model of neuronal damage and in single-channel measurements on isolated mitoplasts. Treatment of neuron-enriched cortical cultures with rotenone, a high affinity inhibitor of the mitochondrial complex I, resulted in a deregulation of the intracellular Ca2+-dynamics, as recorded by live cell imaging. Minocycline (100 microM) and cyclosporin A (2 microM), a known inhibitor of the mitochondrial permeability transition pore, decreased the rotenone-induced Ca2+-deregulation by 60.9% and 37.6%, respectively. Investigations of the mitochondrial permeability transition pore by patch-clamp techniques revealed for the first time a dose-dependent reduction of the open probability by minocycline (IC(50)=190 nM). Additionally, we provide evidence for the high antioxidant potential of MC in our model. In conclusion, the present data substantiate the beneficial properties of minocycline as promising neuroprotectant by its inhibitory activity on the mitochondrial permeability transition pore.

Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue.

INTRODUCTION: Besides the bioavailability of nitric oxide (NO), downstream guanine monophosphate (cGMP) effector proteins are also considered to play a significant role in penile vascular disease. In animal studies, a downregulation of the cGMP-dependent protein kinase-1 (cGKI) alpha isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI alpha and beta isoforms has not been evaluated in human penile erectile tissue. AIM: To evaluate the expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). METHODS: Cryostat sections of HCA and HCC were incubated with primary antibodies directed against alpha-actin, cGMP, eNOS, cGKI, cGKI alpha, and cGKI beta. Visualization of double-labeled immunofluorescent stainings was achieved by laser microscopy. Western blot analysis was performed in order to confirm the expression of cGKI isoforms. MAIN OUTCOME MEASURES: Expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and eNOS in human penile erectile tissue. RESULTS: Immunoreactivities specific for cGKI, cGKI alpha, and cGKI beta were observed within the smooth musculature and the endothelium of cavernous arteries and sinusoids. Double stainings revealed the colocalization of alpha-actin, cGMP, eNOS, and cGKI isoforms. The expression of cGKI isoforms was confirmed by Western blot analysis. CONCLUSIONS: Our results demonstrate, for the first time, the expression of both cGKI alpha and beta isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI alpha and beta provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue.

Genetic polymorphisms in the vascular endothelial growth factor gene and breast cancer risk. The Austrian "tumor of breast tissue: incidence, genetics, and environmental risk factors" study.

PURPOSE: Vascular endothelial growth factor (VEGF) is a key regulator of tumor-induced angiogenesis and is required for growth of tumors. We tested the hypothesis that VEGF gene polymorphisms may be associated with breast cancer. EXPERIMENTAL DESIGN: We performed a case-control study including 804 female incident breast cancer patients and 804 female age-matched healthy control subjects. We selected seven VEGF candidate polymorphisms and determined genotypes by 5'-nuclease (TaqMan) assays. Furthermore, VEGF plasma levels and genotypes were analyzed in a group of 81 healthy volunteers (64 men and 17 women). RESULTS: Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms upstream of the coding sequence (promoter and 5' untranslated region) and two polymorphisms downstream of the coding sequence. None of the single polymorphisms or haplotypes was significantly associated with the presence of breast cancer. After Bonferroni correction for multiple testing, only one statistical signifcant association between VEGF genotypes and haplotypes and tumor characteristics was observed (-634C allele and small tumor size; p < 0.001). In a multivariate regression analysis including sex, age, VEGF genotypes, and haplotypes as covariates and VEGF plasma level as dependent variable, none of the VEGF polymorphism or haplotypes was a significant predictor of VEGF plasma levels. CONCLUSIONS: Our findings do not support the hypothesis that VEGF polymorphisms are associated with breast cancer risk. The association of the VEGF -634C allele with small tumor size is in clear contrast to a previous publication and should be interpreted with caution until replicated by additional studies.

Minocycline, a possible neuroprotective agent in Leber's hereditary optic neuropathy (LHON): studies of cybrid cells bearing 11,778 mutation.

Leber's hereditary optic neuropathy (LHON) is a retinal neurodegenerative disorder caused by mitochondrial DNA point mutations. Complex I of the respiratory chain affected by the mutation results in a decrease in ATP and an increase of reactive oxygen species production. Evaluating the efficacy of minocycline in LHON, the drug increased the survival of cybrid cells in contrast to the parental cells after thapsigargin-induced calcium overload. Similar protection was observed by treatment with cyclosporine A, a blocker of the mitochondrial permeability transition pore (mPTP). Ratiometric Ca(2+) imaging reveals that acetylcholine/thapsigargin triggered elevation of the cytosolic calcium concentration is alleviated by minocycline and cyclosporine A. The mitochondrial membrane potential of LHON cybrids was significantly conserved and the active-caspase-3/procaspase-3 ratio was decreased in both treatments. Our observations show that minocycline inhibits permeability transition induced by thapsigargin in addition to its antioxidant effects. In relation with its high safety profile, these results would suggest minocycline as a promising neuroprotective agent in LHON.

Inhibiting effect of minocycline on the regeneration of peripheral nerves.

The effect of minocycline on nerve regeneration was studied in a rat model of acute sciatic nerve injury, in which the injury was caused by resection and reimplantation of the right sciatic nerve. Immunohistochemical and molecular biological methods, as well as morphometric and electron microscopic techniques, were used. Compared with uninjured and PBS-treated injured nerves, the minocycline-treated injured nerve showed: (i) a decrease in macrophage recruitment and activation, probably resulting from inhibition of blood-brain-barrier break-down via reduced MMP2 and MMP9 induction, inhibition of revascularization via additional reduction of VEGF induction, and inhibition of inducible NO synthase (iNOS) induction; (ii) reduced activation of phagocytic Schwann cells, probably by inhibition of iNOS, MMP2 and MMP9 expression; (iii) a slowed Wallerian degeneration; and subsequently, (iv) a diminished nerve regeneration. Macrophages, especially their function in the removal of cellular debris and formation of a microenvironment beneficial for nerve regeneration, are strongly implicated in constructive events after nerve injuries. Therefore, we suggest that additional research into optimizing minocycline intervention for treatment of neurodegenerative diseases is needed before further clinical trials are performed.

Frontal recess anatomy study by endoscopic dissection in cadavers.

INTRODUCTION AND AIMS: The frontal sinus ostium is frequently difficult to recognize because of anatomical structures that hide it. The objective of the present study was to identify and describe the frontal recess anatomy that impairs the endoscopic recognition of the frontal sinus ostium. STUDY DESIGN AND METHODS: A prospective study was conducted by consecutive endoscopic dissections of 32 cadavers (59 sides), 10 (31.25%) females and 22 (68.75%) males. After resection of the lower portion of the uncinate process, with preservation of its upper insertion, we evaluated which anatomical structures needed to be removed for complete visualization of the frontal sinus ostium. RESULTS AND CONCLUSIONS: Visualization of the frontal sinus ostium after resection of the lower portion of the uncinate process was possible in only 11 (18.64%) nasal cavities. The uncinate process (terminal recess) was the main anatomical structure that impaired the recognition of the frontal sinus ostium, present in 45 (76.27%) nasal cavities, followed by the ethmoid bulla (16.95%) and agger nasi cells (6.78%).

The effects of p-chloroamphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (ecstasy) on the gene expression of cytoskeletal proteins in the rat brain.

Repeated administration of beta-phenylalkylamines is known to produce neuronal changes in the central and peripheral nervous systems of mammals. It is suggested that various components of the cytoskeleton undergo profound alterations after amphetamine use and misuse, contributing to behavioral changes and neurotoxicity. Here we studied the expression of microtubule-associated protein 2 (MAP2) and beta-actin after repeated intraperitoneal applications with equimolar doses of p-chloroamphetamine (PCA), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) in the brain of male Wistar rats. Effective (molecular) pharmacological doses (ED) were derived and used for the calculation of (molecular) pharmacological indices (PI). Besides clear but different dose-response curves on the toxicity of the drugs, in situ hybridization and Western blot analysis revealed that repeated administration of these compounds resulted in different substance- and dose-dependent changes in MAP2 gene expression, e.g. in the frontoparietal somatosensoric cortex. In contrast, the expression of beta-actin was not influenced by any of the compounds at the dose levels tested. Lethal doses were determined with 2.1 (PCA), >5.1 (METH) and 8.4 mg/kg/day (MDMA). Linear and non-linear repeat-dose lethality was observed for MDMA and PCA, respectively, whereas METH was non-lethal in the dose range used. Values for ED(MAP2) were 0.3, 0.52 and >16.8 mg/kg/day, and therefore those for PI(MAP2) were 20, 4, and 0.5 for METH, PCA and MDMA, respectively. Although the results on mortality did not reflect changes in MAP2 gene expression, they suggest a remarkable difference for those amphetamines without substituents or with a halogen atom at the paraposition of the benzene ring, such as METH or PCA, when compared with MDMA-like substances.

Splice-isoform specific immunolocalization of neuronal nitric oxide synthase in mouse and rat brain reveals that the PDZ-complex-building nNOSalpha beta-finger is largely exposed to antibodies.

Knock out mice deficient for the splice-isoform alphaalpha of neuronal nitric oxide synthase (nNOSalphaalpha) display residual nitric oxide synthase activity and immunosignal. To attribute this signal to the two minor neuronal nitric oxide synthase splice variants, betabeta and gammagamma, we generated isoform-specific anti-peptide antibodies against the nNOSalphaalpha specific betabeta-finger motif involved in PDZ domain scaffolding and the nNOSbetabeta specific N-terminus. The nNOSalphaalpha betabeta-finger-specific antibody clearly recognized the 160-kDa band of recombinant nNOSalphaalpha on Western blots. Using immunocytochemistry, this antibody displayed, in rats and wild-type mice, a labeling pattern similar to but not identical with that obtained using a commercial pan-nNOS antibody. This similarity indicates that the majority of immunocytochemically detectable nNOS is not likely to be complexed with PDZ-domain proteins via the betabeta-finger motif. This conclusion was confirmed by the inhibition of PSD-95/nNOS interaction by the nNOSalphaalpha betabeta-finger antibody in pull-down assays. By contrast, nNOSalphaalpha betabeta-finger labeling was clearly reduced in hippocampal and cortical neuropil areas enriched in NMDA receptor complex containing spine synapses. In nNOSalphaalpha knock out mice, nNOSalphaalpha was not detectable, whereas the pan-nNOS antibody showed a distinct labeling of cell bodies throughout the brain, most likely reflecting betabeta/gammagamma-isoforms in these cells. The nNOSbetabeta antibody clearly detected bacterial expressed nNOSbetabeta fusion protein and nNOSbetabeta in overexpressing HEK cells by Western blotting. Immunocytochemically, individual cell bodies in striatum, cerebral cortex, and in some brain stem nuclei were labeled in knock out but not in wild-type mice, indicating an upregulation of nNOSbetabeta in nNOSalphaalpha deficient animals.

Estudo da anatomia do recesso frontal por meio de dissecção endoscópica em cadáveres / Frontal recess anatomy study by endoscopic dissection in cadavers

INTRODUÇÃO E OBJETIVO: O óstio do seio frontal freqüentemente apresenta difícil reconhecimento devido a estruturas anatômicas que encobrem sua visibilização. O objetivo principal desse estudo foi identificar e descrever as estruturas anatômicas do recesso frontal que dificultam o reconhecimento do óstio do seio frontal. CASUíSTICA E MÉTODOS: Foi realizado um estudo prospectivo por meio de dissecção endoscópica consecutiva de 32 cadáveres (59 fossas nasais), 10 (31,25 por cento) do sexo feminino e 22 (68,75 por cento) do sexo masculino. Após exérese endoscópica da porção inferior do processo uncinado, com a preservação da sua inserção superior, avaliamos quais estruturas anatômicas necessitavam ser removidas até a completa visibilização endonasal do óstio do seio frontal. RESULTADOS E CONCLUSÃO: A visibilização do óstio do seio frontal após a exérese da porção inferior do processo uncinado foi possível em apenas 11 (18,64 por cento) fossas nasais. O processo uncinado (recesso terminal) representou a principal estrutura anatômica que dificultou o reconhecimento endonasal do óstio do seio frontal, ocorrendo em 45 (76,27 por cento) fossas nasais, seguido pela bolha etmoidal (16,95 por cento) e a célula agger nasi (6,78 por cento).

INTRODUCTION AND AIMS: The frontal sinus ostium is frequently difficult to recognize because of anatomical structures that hide it. The objective of the present study was to identify and describe the frontal recess anatomy that impairs the endoscopic recognition of the frontal sinus ostium. STUDY DESIGN AND METHODS: A prospective study was conducted by consecutive endoscopic dissections of 32 cadavers (59 sides), 10 (31.25 percent) females and 22 (68.75 percent) males. After resection of the lower portion of the uncinate process, with preservation of its upper insertion, we evaluated which anatomical structures needed to be removed for complete visualization of the frontal sinus ostium. RESULTS AND CONCLUSIONS: Visualization of the frontal sinus ostium after resection of the lower portion of the uncinate process was possible in only 11 (18.64 percent) nasal cavities. The uncinate process (terminal recess) was the main anatomical structure that impaired the recognition of the frontal sinus ostium, present in 45 (76.27 percent) nasal cavities, followed by the ethmoid bulla (16.95 percent) and agger nasi cells (6.78 percent).