Corticosteroide por via espinal é uma das alternativas no processo de tratamento da dor radicular quando o tratamento conservador falhou. Sua administração por via epidural vem sendo reavaliada devido ao risco de sequelas, provenientes da obstrução de vasos sanguíneos, associadas a outros efeitos adversos próprios dos corticosteroides. O presente estudo visou avaliar o efeito analgésico da administração de diferentes corticosteroides, exemplificados pela dexametasona e pela betametasona, administrados por via epidural. Vinte e seis pacientes portadores de dor neuropática secundária à hérnia de disco participaram do estudo. A punção sacral foi realizada com combinação de 40 mg de lidocaína, 30 µg de clonidina e 10 mg de dexametasona ou 10 mg de betametasona, diluídos para volume final 10 ml, com solução fisiológica a 0,9%, após comprovação com contraste não-iodado do perfeito posicionamento da agulha no espaço epidural. Este procedimento foi repetido uma vez por semana por 2 semanas seguidas, e após um intervalo de 3 semanas foi realizado mais duas vezes, uma vez por semana, sendo o total de 4 procedimentos por paciente. Treze pacientes iniciaram com dexametasona epidural durante as primeiras duas semanas, e prosseguiram com betametasona após período de descanso de três semanas, sendo que cada paciente atuou como seu próprio controle. Os pacientes foram avaliados em relação à analgesia, incidência de efeitos adversos e alteração das concentrações plasmáticas de íons, cortisol, adrenocorticotrofina e glicemia. Vinte e três pacientes completaram o estudo. Cada paciente foi o seu próprio controle e, no mesmo paciente, o efeito analgésico da dexametasona foi superior ao da betametasona. (p<0,05). Cortisol e adrenocorticotrofina plasmáticos reduziram no sétimo dia após realização do bloqueio (p<0,05), As demais medidas de concentrações plasmáticas de íons Na+, K+, Ca++, glicemia inicial, pós-prandial e hemoglobina glicada foram semelhantes entre os grupos, e sem alteração quando comparados com valores iniciais (p>0,05). Ambos grupos relataram insônia relativa nos primeiros dias pós-bloqueio (p<0,05). Não houve alteração de peso corporal e da pressão arterial durante o tratamento entre os fármacos avaliados (p>0,05). Entretanto, 3 pacientes que receberam dexametasona e 2 que receberam betametasona inicialmente, apresentam medida de pressão ocular aumentada (p<0,05). Como conclusões, a analgesia da dexametasona foi superior quando comparada à da betametasona, (p<0,05). Entretanto ambos grupos apresentaram aumento da pressão ocular e prejuízo do sono noturno, não relevante este último. Finalmente, uma vez que a dexametasona foi superior à betametasona em relação à analgesia e demonstrada ser mais segura em relação à formação de agregados, sugere-se a dexametasona como escolha. / Although the primarily indication of epidural corticosteroids as part of the treatment of acute neuropathic pain when the conservative treatment have failed, recently there have been concerns related to which corticosteroid would be the best indication, as there is the risk of particulate aggregation and serious adverse effects secondary to their own pharmacological properties or intra vessel aggregation and obliteration, as well their efficacy as analgesics. This actual study was designed to evaluate two different corticosteroids, i.e., dexamethasone and betamethasone, as coajuvants in epidural management of acute radicular pain. Twenty-six patients with history of neuropathic pain secondary to disc herniation acted as their own control related to the epidural administration of dexamethasone and betamethasone. Sacral puncture was performed with a combination of 40 mg of lidocaine, 30 µg of clonidine and 10 mg of dexamethasone or 10 mg of betamethasone, diluted to final volume 10 ml with 0.9% physiological solution after non-iodinated contrast of the perfect positioning of the needle in the epidural space.Thirteen patients have started with dexamethasone during the first two weekly procedures, and after 3 weeks of wash-out were submitted to two weekly sequence of sacral betamethasone. The other patients have started with epidural betamethasone, followed by dexamethasone after 3-week rest. Each patient acted as its own control. Patients were evaluated related to analgesia, blood pressure, weight gain, adverse effects and plasmatic measurements of ions, glicemia, ACTH and cortisol. Twenty-three patients completed the study. The analgesic effect was higher when dexamethasone was used in the same patient (p <0.05) Plasma cortisol and ACTH reduced on the 7th day after the block (p<0.05). The plasmatic concentrations of the ions Na+, K+, Ca++, control and post-prandial glicemia, blood pressure, weight were similar between groups and did no differ from initial control values (p>0.05). Both groups reported relative insomnia in the first post-blockade days (P <0.05). However, 3 patients that received dexamethasone and 2 that received betamethasone had ocular pressure increase (p<0.05). As conclusions, both drugs resulted in still unaware increase in ocular pressure and sleep disturbance. Because dexamethasone analgesia was superior and there were no differences regarding adverse effects between either epidural betamethasone or dexamethasone, based on the literature, it would be more appropriate the utilization of dexamethasone.

Diabetes is a chronic metabolic disorder whereby the body loses its ability to maintain normal glucose levels. Despite of development of implantable glucose sensors in long periods, none of the biosensors are capable of continuously monitoring glucose levels during long-term implantation reliably. Progressive loss of sensor function occurs due in part to biofouling and to the consequences of a foreign body response such as inflammation, fibrosis, and loss of vasculature. In order to improve the function and lifetime of implantable glucose sensors, a new 3D porous and bio-stable collagen scaffold has been developed to improve the biocompatibility of implantable glucose sensors. The novel collagen scaffold was crosslinked using nordihydroguaiaretic acid (NDGA) to enhance biostability. NDGA-treated collagen scaffolds were stable without any physical deformation in the subcutaneous tissue of rats for 4 weeks. The scaffold application does not impair the function of our sensor. The effect of the scaffolds on sensor function and biocompatibility was examined during long-term in vitro and in vivo experiments and compared with control bare sensors. The sensitivity of the short sensors was greater than the sensitivity of long sensors presumably due to less micro-motions in the sub-cutis of the rats. The NDGA-crosslinked scaffolds induced much less inflammation and retained their physical structure in contrast to the glutaraldehyde (GA)-crosslinked scaffolds. We also have developed a new dexamethasone (Dex, anti-inflammatory drug)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres/porous collagen scaffold composite for implantable glucose sensors. The composite system showed a much slower and sustained drug release than the standard microspheres. The composite system was also shown to not significantly affect the function of the sensors. The sensitivity of the sensors with the composite system in vivo remained higher than for sensors without the composites (no scaffold, scaffold without microspheres). Histology showed that the inflammatory response to the Dex-loaded composite was much lower than for the control scaffold. The Dex-loaded composite system might be useful to reduce inflammation to glucose sensors and therefore extend their function and lifetime.

Introduction: Diagnosed adrenal incidentalomas (AI) are increasing and dexamethasonesuppression test (DST) is gold standard for detection of excess cortisol production. Patients canbe categorized into three groups based on the DST level; non-functional adrenal adenomas(NFAA), possible autonomous cortisol secretion (PACS) and autonomous cortisol secretion(ACS), the latter two associated with increased risk of cardiovascular morbidity and mortality. Aim: The aim of this study was to compare cardiovascular morbidity and mortality in patientswith adrenal incidentalomas with and without hypercortisolemia defined by the EuropeanSociety of Endocrinology (2016) guidelines. Method: Retrospectively 160 consecutive patient charts between 2008 and 2015 were reviewedand 59 included. They were further categorized in NFAA (n = 37) or PACS (n = 22). Patientswith signs and symptoms of hormonal overproduction or AI found during malignancyinvestigations were excluded. Due to strict adherence to inclusion and exclusion criteria, onlyone case of ACS was found and excluded due to ethical reason. Results: Increased prevalence of type 2 diabetes in PACS group at baseline. No difference incardiovascular disease or mortality between the groups could be seen after mean follow up of7 years. Three (8%) patients in the NFAA group deceased, all of malignancy. In the PACSgroup, five (23%) deceased. Cause of death was cerebral infarction (n = 2), malignancy (n =1)and other causes (n =2). Conclusion: No significant difference of cardiovascular morbidity and mortality could be seenbetween NFAA and PACS during follow up. A prospective multicentre study is needed toidentify the long-term outcomes.

Cryptosporidium parvum is a coccidian protozoan that colonizes epithelial cells lining respiratory and digestive tracts of animals and humans. Cryptosporidiosis is a well-recognized zoonotic disease infecting primarily neonates and immunocompromised hosts, including human immunodeficiency virus-infected patients. Clinical disease is manifested as a chronic diarrheal illness that is self-limiting in immunocompetent hosts and prolonged and often life-threatening in hosts with compromised immune systems. The lack of a suitable small animal model for screening anti-cryptosporidial drugs and for examining the pathogenicity and immunobiology of chronic cryptosporidosis was the impetus for this research effort. The objectives of the present study were three-fold: to characterize chronic Cryptosporidium parvum infections in dexamethasone-immunosuppressed mice; evaluate the effects of Cryptosporidium parvum and dexamethasone on B and T lymphocyte proliferation; and determine the effects of the immunomodulator dehydroepiandrosterone on oocyst shedding intensities of mice infected with Cryptosporidium parvum Adult C57BL/6N mice were immunosuppressed with the synthetic glucocorticoid dexamethasone, then infected with Cryptosporidium parvum (106 oocysts/mouse) and investigated for their ability to sustain a four-month chronic infection. Dexamethasone was administered intraperitoneally (125μ/mouse/day) or orally (8μ/ml) in the drinking water ad libitum. Infection chronicity was characterized by evaluating mouse mortality, oocyst excretion in the feces, tissue distribution of the parasite, and the parasite-induced pathology. A progressive infection with Cryptosporidium parvum occurred in mice immunosuppressed intraperitoneally and orally as long as dexamethsone was administered. Mice receiving dexamethasone given intraperitoneally had a shorter prepatent period and a more consistent, although cyclic, oocyst shedding pattern when compared with mice given dexamethasone orally. Mice given dexamethasone orally exhibited a delayed prepatent period, with a steady increase in oocyst shedding. All mice receiving dexamethasone orally died within three months following oocyst inoculation. Clinical signs included dehydration, icterus, and reduction in spleen and body weights. Clinical signs were more abrupt in mice receiving oral dexamethasone. Parasite colonization involved the entire intestinal tract, including the pyloric ring and Peyer's patches, but was the heaviest in the terminal ileum. Parasites were present in the lungs, gallbladder, and pancreatic ducts. Pathologic abnormalities were isolated to the terminal small intestine and included blunting and fusion of intestinal villi and crypt hyperplasia. Cryptosporidium parvum and dexamethasone administered in vivo reduced B and T lymphocyte responses to the mitogens lipopolysaccharide and concanavalin A. Dehydroepiandrosterone and dehydroepiandrosterone-sulfate resulted in no significant reductions in cryptosporidial activity as determined by oocyst shedding in the feces.

<p>Multiple myeloma (MM) is a hematological tumor of plasma blast/plasma cell origin heterogeneous with respect to the morphological differentiation stage of the tumor cells, genetic alterations and course of disease. A challenge in MM research is to overcome resistance to therapy, which inevitably arises. In this thesis, we have used different strategies to sensitize MM cells to apoptosis and explored possible mechanisms of apoptotic control by the insulin-like growth factor-1 receptor (IGF-1R) survival pathway.</p><p>mTOR is a key molecule in the regulation of translation activated by survival signaling pathways in MM. We demonstrate that the mTOR-inhibitor rapamycin alone induced apoptosis in primary MM cells. In addition, rapamycin sensitized MM cells to apoptosis induced by dexamethasone, a glucocorticoid frequently used in MM therapy. MM survival factors IGF-1 and IL-6 could neither restore phosphorylation of the mTOR target p70S6K, nor cell growth inhibited by rapamycin and dexamethasone.</p><p>To study the regulation of inhibitors of apoptosis (IAP), we induced apoptosis and cell cycle arrest with dexamethasone and simultaneously abrogated IGF-1R signaling using the antagonistic antibody αIR3 or the selective IGF-1R inhibitor picropodophyllin (PPP). Dexamethasone transiently up-regulated c-IAP2. The subsequent down-regulation of c-IAP2 and XIAP was associated with the onset of apoptosis. c-IAP2 and XIAP levels further decreased when enhancing dexamethasone-induced apoptosis using αIR3 or PPP indicating a role for IAPs in regulating resistance to apoptosis in MM.</p><p>Finally, we explored glycogen synthase kinase (GSK)3 as a possible pro-apoptotic molecule and its role in regulating sensitization to apoptosis. We show that inhibition of GSK3 counteracts growth inhibition induced by dexamethasone alone and in combinatorial treatments with inhibitors against PI 3-kinase, mitogen-activated protein kinase (MEK), mTOR and IGF-1R. CT99021 also reversed cell cycle arrest induced by LY294002 or rapamycin. Importantly, the GSK3 inhibitor CT99021 sustained viability in untreated and dexamethasone-treated primary MM cells.</p>

Multiple myeloma (MM) is a hematological tumor of plasma blast/plasma cell origin heterogeneous with respect to the morphological differentiation stage of the tumor cells, genetic alterations and course of disease. A challenge in MM research is to overcome resistance to therapy, which inevitably arises. In this thesis, we have used different strategies to sensitize MM cells to apoptosis and explored possible mechanisms of apoptotic control by the insulin-like growth factor-1 receptor (IGF-1R) survival pathway. mTOR is a key molecule in the regulation of translation activated by survival signaling pathways in MM. We demonstrate that the mTOR-inhibitor rapamycin alone induced apoptosis in primary MM cells. In addition, rapamycin sensitized MM cells to apoptosis induced by dexamethasone, a glucocorticoid frequently used in MM therapy. MM survival factors IGF-1 and IL-6 could neither restore phosphorylation of the mTOR target p70S6K, nor cell growth inhibited by rapamycin and dexamethasone. To study the regulation of inhibitors of apoptosis (IAP), we induced apoptosis and cell cycle arrest with dexamethasone and simultaneously abrogated IGF-1R signaling using the antagonistic antibody αIR3 or the selective IGF-1R inhibitor picropodophyllin (PPP). Dexamethasone transiently up-regulated c-IAP2. The subsequent down-regulation of c-IAP2 and XIAP was associated with the onset of apoptosis. c-IAP2 and XIAP levels further decreased when enhancing dexamethasone-induced apoptosis using αIR3 or PPP indicating a role for IAPs in regulating resistance to apoptosis in MM. Finally, we explored glycogen synthase kinase (GSK)3 as a possible pro-apoptotic molecule and its role in regulating sensitization to apoptosis. We show that inhibition of GSK3 counteracts growth inhibition induced by dexamethasone alone and in combinatorial treatments with inhibitors against PI 3-kinase, mitogen-activated protein kinase (MEK), mTOR and IGF-1R. CT99021 also reversed cell cycle arrest induced by LY294002 or rapamycin. Importantly, the GSK3 inhibitor CT99021 sustained viability in untreated and dexamethasone-treated primary MM cells.

No description available.

Background: The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. Objective: The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. Methods: This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15mg/kg, maximum 8mg). Blood glucose levels were measured up to 6 hours. Standard deviation scores (SDS) were calculated using age- and gender-specific BMI percentiles, p<0.05. Results: 62 children (11.5±2.9years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose level increased from 5.52±0.52 to 6.74±0.84mmol/l 6h after dexamethasone without correlation to the BMI-SDS. Conclusions: This study shows an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone but no BMI-dependent effect in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

This thesis contributes to the growing body of gender-specific health research by integrating both psychological and neuroendocrine data to assess the impacts of stress and violence on women's health. Women seeking support for intimate partner violence (IPV) were compared with women seeking support for non-interpersonal stressors (stress associated with immigration). Psychological measures included perceived stress and entrapment and mental defeat (EMD) scores as well as assessment of Axis I disorders. Neuroendocrine measures included basal levels of salivary cortisol and percent suppression of cortisol after the low-dose dexamethasone suppression test (DST). Positive relationships were found between experiences of IPV and perceived stress, EMD and Axis I diagnosis. The neuroendocrine measures did not differentiate IPV from non-interpersonal stressors and both groups showed hypersuppression of cortisol after the DST. IPV influences women's perceptions about EMD and perceived stress. By integrating neuroendocrine and psychological measures, further development of gender-specific stress models may occur.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.