Safety and efficacy of pimecrolimus versus vehicle for the treatment of atopic dermatitis in adults and paediatric population: a systematic review and meta-analysis.

Atopic dermatitis remains a widespread problem affecting various populations globally. While numerous treatment options have been employed, pimecrolimus remains a potent and viable option. Recently, there has been increasing interest in comparing the safety and efficacy of pimecrolimus with its vehicle. Methods: The authors conducted a comprehensive search of several databases, including PubMed, COCHRANE, MEDLINE, and Cochrane Central, from inception to May 2022, using a wide search strategy with Boolean operators. The authors also employed backward snowballing to identify any studies missed in the initial search. The authors included randomized controlled trials in our meta-analysis and extracted data from the identified studies. The authors used Review Manager (RevMan) Version 5.4 to analyze the data, selecting a random-effects model due to observed differences in study populations and settings. The authors considered a P-value of 0.05 or lower to be statistically significant. Results: The authors initially identified 211 studies, of which 13 randomized controlled trials involving 4180 participants were selected for analysis. Our pooled analysis revealed that pimecrolimus 1% was more effective at reducing the severity of atopic dermatitis than its vehicles. However, no significant difference was observed in adverse effects between pimecrolimus and vehicle, except for pyrexia, nasopharyngitis, and headache, which were increased with pimecrolimus. Conclusion: Our meta-analysis showed that pimecrolimus 1% is more effective than vehicle, although the safety profile remains inconclusive. Pimecrolimus reduced the Investigator's Global Assessment score, Eczema Area and Severity Index score, and severity of pruritus when compared to its vehicle, indicating a higher efficacy profile. This is one of the first meta-analyses to assess the efficacy and safety profile of pimecrolimus 1% against a vehicle and may assist physicians in making informed decisions.

Multifocal Nodular Fatty Sparing Mimicking Hepatic Tumors.

Hepatic steatosis is frequent; however, it may present with unusual patterns, resulting in a diagnostic dilemma. Herein, we present a case of fatty liver and multifocal nodular hepatic lesions that were found to be due to multifocal nodular fatty sparing, which mimics metastasis or primary multifocal tumors. As the differential diagnosis of such lesions can be difficult based on ultrasound alone, the knowledge of Magnetic Resonance Imaging (MRI) findings is crucial. It enables the radiologists to make the correct diagnosis and alleviate the patient from unnecessary biopsies.

Comparative analysis of various sources of selenium on the growth performance and antioxidant status in broilers under heat stress / Análise comparativa de várias fontes de selênio no desempenho de crescimento e status antioxidante em frangos de corte sob estresse térmico

The supplementation of Selenium-enriched probiotics is effective in reducing oxidative stress and maintaining meat quality stability in broiler chicken especially under heat stress. An experimental study was conducted to perform Comparative analysis of Selenium yeast with inorganic Se in broilers under heat stress. A total of 120 broilers chicks of one day were assigned to 4 groups each consisting 30 chicks fed on same basal diet but different selenium sources. The basal diet of group D1 was not supplemented with Se source (Negative control), group D2 basal diet was supplemented with inorganic selenium (Sodium selenite 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase), group D3 basal diet was supplemented with commercially available organic selenium (Seleno-methionine 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase) and group D4 basal diet was supplemented with self-developed organic selenium (Se-enriched yeast 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase). The performance parameters i.e. feed intake (FI), live body weight (BW) and FCR were not significantly (p>0.05) effected by selenium supplementation in the starter phase but were significantly (p<0.05) effected in the finisher phase. Selenium supplementation significantly (p<0.05) effected serum Se level in different supplemented groups. Higher serum Se value (58.20±0.06) was recorded in D4 group. Similarly significantly lower selenium value was recorded for D4 and higher was recorded for D1 (11.36±0.08). However lower serum Paraoxonase (PON) value was recorded for D4 (13.24±0.01) and higher for D1 (13.33±0.03). Comparatively self-developed Se enriched yeast increased the Se accumulation and improved antioxidant system. Glutathione peroxidase (GPx) was found higher in D4 (12.333±0.03) followed by D3, D2 and D1 respectively. Whereas superoxide dismutase (SOD) was significantly lower (p<0.05) in D4 (0.1437±0.003) followed by D3 (0.1457±0.002). Selenium supplementation increased the [...].

A suplementação de probióticos enriquecidos com selênio é eficaz na redução do estresse oxidativo e na manutenção da estabilidade da qualidade da carne em frangos de corte, especialmente sob estresse por calor. Um estudo experimental foi conduzido para realizar uma análise comparativa da levedura selênio com o Se inorgânico em frangos de corte sob estresse térmico. Um total de 120 pintos de um dia foi dividido em 4 grupos, cada um consistindo de 30 pintos alimentados com a mesma dieta basal, mas com diferentes fontes de selênio. A dieta basal do grupo D1 não foi suplementada com fonte de Se (controle negativo), a dieta basal do grupo D2 foi suplementada com selênio inorgânico (selenito de sódio 0,22 mg / kg fase inicial e 0,15 mg / kg fase finalizadora), a dieta basal do grupo D3 foi suplementada com selênio orgânico disponível comercialmente (fase inicial de seleno-metionina 0,22 mg / kg e fase finalizadora de 0,15 mg / kg) e a dieta basal do grupo D4 foi suplementada com selênio orgânico autodesenvolvido (fermento enriquecido com Se 0,22 mg / kg fase inicial e 0,15 mg / kg fase finalizadora). Os parâmetros de desempenho, ou seja, consumo de ração (FI), peso corporal vivo (PC) e FCR não foram significativamente (p > 0,05) afetados pela suplementação de selênio na fase inicial, mas foram significativamente (p < 0,05) afetados na fase final. A suplementação de selênio afetou significativamente (p < 0,05) o nível de Se sérico em diferentes grupos suplementados. O maior valor de Se sérico (58,20 ± 0,06) foi registrado no grupo D4. Da mesma forma, valor de selênio significativamente menor foi registrado para D4 e maior foi registrado para D1 (11,36 ± 0,08). No entanto, um valor mais baixo de Paraoxonase (PON) sérica foi registrado para D4 (13,24 ± 0,01) e mais alto para D1 (13,33 ± 0,03). A levedura enriquecida com Se comparativamente autodesenvolvida aumentou o acúmulo de Se e melhorou o sistema [...].

Comparative analysis of various sources of selenium on the growth performance and antioxidant status in broilers under heat stress

Abstract The supplementation of Selenium-enriched probiotics is effective in reducing oxidative stress and maintaining meat quality stability in broiler chicken especially under heat stress. An experimental study was conducted to perform Comparative analysis of Selenium yeast with inorganic Se in broilers under heat stress. A total of 120 broilers chicks of one day were assigned to 4 groups each consisting 30 chicks fed on same basal diet but different selenium sources. The basal diet of group D1 was not supplemented with Se source (Negative control), group D2 basal diet was supplemented with inorganic selenium (Sodium selenite 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase), group D3 basal diet was supplemented with commercially available organic selenium (Seleno-methionine 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase) and group D4 basal diet was supplemented with self-developed organic selenium (Se-enriched yeast 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase). The performance parameters i.e. feed intake (FI), live body weight (BW) and FCR were not significantly (p>0.05) effected by selenium supplementation in the starter phase but were significantly (p 0.05) effected in the finisher phase. Selenium supplementation significantly (p 0.05) effected serum Se level in different supplemented groups. Higher serum Se value (58.20±0.06) was recorded in D4 group. Similarly significantly lower selenium value was recorded for D4 and higher was recorded for D1 (11.36±0.08). However lower serum Paraoxonase (PON) value was recorded for D4 (13.24±0.01) and higher for D1 (13.33±0.03). Comparatively self-developed Se enriched yeast increased the Se accumulation and improved antioxidant system. Glutathione peroxidase (GPx) was found higher in D4 (12.333±0.03) followed by D3, D2 and D1 respectively. Whereas superoxide dismutase (SOD) was significantly lower (p 0.05) in D4 (0.1437±0.003) followed by D3 (0.1457±0.002). Selenium supplementation increased the birds survival rate. Birds fed on Se enriched yeast showed higher Se deposition and better antioxidant capacity as compared to other sources of selenium. Se-enriched yeast displayed an improved result on Se deposition in tissues, and oxidative capacity, meat tenderness and immune response level as compared to other sources of selenium.

Resumo A suplementação de probióticos enriquecidos com selênio é eficaz na redução do estresse oxidativo e na manutenção da estabilidade da qualidade da carne em frangos de corte, especialmente sob estresse por calor. Um estudo experimental foi conduzido para realizar uma análise comparativa da levedura selênio com o Se inorgânico em frangos de corte sob estresse térmico. Um total de 120 pintos de um dia foi dividido em 4 grupos, cada um consistindo de 30 pintos alimentados com a mesma dieta basal, mas com diferentes fontes de selênio. A dieta basal do grupo D1 não foi suplementada com fonte de Se (controle negativo), a dieta basal do grupo D2 foi suplementada com selênio inorgânico (selenito de sódio 0,22 mg / kg fase inicial e 0,15 mg / kg fase finalizadora), a dieta basal do grupo D3 foi suplementada com selênio orgânico disponível comercialmente (fase inicial de seleno-metionina 0,22 mg / kg e fase finalizadora de 0,15 mg / kg) e a dieta basal do grupo D4 foi suplementada com selênio orgânico autodesenvolvido (fermento enriquecido com Se 0,22 mg / kg fase inicial e 0,15 mg / kg fase finalizadora). Os parâmetros de desempenho, ou seja, consumo de ração (FI), peso corporal vivo (PC) e FCR não foram significativamente (p > 0,05) afetados pela suplementação de selênio na fase inicial, mas foram significativamente (p 0,05) afetados na fase final. A suplementação de selênio afetou significativamente (p 0,05) o nível de Se sérico em diferentes grupos suplementados. O maior valor de Se sérico (58,20 ± 0,06) foi registrado no grupo D4. Da mesma forma, valor de selênio significativamente menor foi registrado para D4 e maior foi registrado para D1 (11,36 ± 0,08). No entanto, um valor mais baixo de Paraoxonase (PON) sérica foi registrado para D4 (13,24 ± 0,01) e mais alto para D1 (13,33 ± 0,03). A levedura enriquecida com Se comparativamente autodesenvolvida aumentou o acúmulo de Se e melhorou o sistema antioxidante. A glutationa peroxidase (GPx) foi encontrada maior em D4 (12,333 ± 0,03) seguido por D3, D2 e D1 respectivamente. Enquanto a superóxido dismutase (SOD) foi significativamente menor (p 0,05) em D4 (0,1437 ± 0,003) seguido por D3 (0,1457 ± 0,002). A suplementação de selênio aumentou a taxa de sobrevivência da ave. Aves alimentadas com levedura enriquecida com Se apresentaram maior deposição de Se e melhor capacidade antioxidante em comparação com outras fontes de selênio. A levedura enriquecida com Se apresentou um resultado melhorado na deposição de Se nos tecidos, capacidade oxidativa, maciez da carne e nível de resposta imune em comparação com outras fontes de selênio.

Comparative analysis of various sources of selenium on the growth performance and antioxidant status in broilers under heat stress / Análise comparativa de várias fontes de selênio no desempenho de crescimento e status antioxidante em frangos de corte sob estresse térmico

Abstract The supplementation of Selenium-enriched probiotics is effective in reducing oxidative stress and maintaining meat quality stability in broiler chicken especially under heat stress. An experimental study was conducted to perform Comparative analysis of Selenium yeast with inorganic Se in broilers under heat stress. A total of 120 broilers chicks of one day were assigned to 4 groups each consisting 30 chicks fed on same basal diet but different selenium sources. The basal diet of group D1 was not supplemented with Se source (Negative control), group D2 basal diet was supplemented with inorganic selenium (Sodium selenite 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase), group D3 basal diet was supplemented with commercially available organic selenium (Seleno-methionine 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase) and group D4 basal diet was supplemented with self-developed organic selenium (Se-enriched yeast 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase). The performance parameters i.e. feed intake (FI), live body weight (BW) and FCR were not significantly (p>0.05) effected by selenium supplementation in the starter phase but were significantly (p<0.05) effected in the finisher phase. Selenium supplementation significantly (p<0.05) effected serum Se level in different supplemented groups. Higher serum Se value (58.20±0.06) was recorded in D4 group. Similarly significantly lower selenium value was recorded for D4 and higher was recorded for D1 (11.36±0.08). However lower serum Paraoxonase (PON) value was recorded for D4 (13.24±0.01) and higher for D1 (13.33±0.03). Comparatively self-developed Se enriched yeast increased the Se accumulation and improved antioxidant system. Glutathione peroxidase (GPx) was found higher in D4 (12.333±0.03) followed by D3, D2 and D1 respectively. Whereas superoxide dismutase (SOD) was significantly lower (p<0.05) in D4 (0.1437±0.003) followed by D3 (0.1457±0.002). Selenium supplementation increased the bird's survival rate. Birds fed on Se enriched yeast showed higher Se deposition and better antioxidant capacity as compared to other sources of selenium. Se-enriched yeast displayed an improved result on Se deposition in tissues, and oxidative capacity, meat tenderness and immune response level as compared to other sources of selenium.

Resumo A suplementação de probióticos enriquecidos com selênio é eficaz na redução do estresse oxidativo e na manutenção da estabilidade da qualidade da carne em frangos de corte, especialmente sob estresse por calor. Um estudo experimental foi conduzido para realizar uma análise comparativa da levedura selênio com o Se inorgânico em frangos de corte sob estresse térmico. Um total de 120 pintos de um dia foi dividido em 4 grupos, cada um consistindo de 30 pintos alimentados com a mesma dieta basal, mas com diferentes fontes de selênio. A dieta basal do grupo D1 não foi suplementada com fonte de Se (controle negativo), a dieta basal do grupo D2 foi suplementada com selênio inorgânico (selenito de sódio 0,22 mg / kg fase inicial e 0,15 mg / kg fase finalizadora), a dieta basal do grupo D3 foi suplementada com selênio orgânico disponível comercialmente (fase inicial de seleno-metionina 0,22 mg / kg e fase finalizadora de 0,15 mg / kg) e a dieta basal do grupo D4 foi suplementada com selênio orgânico autodesenvolvido (fermento enriquecido com Se 0,22 mg / kg fase inicial e 0,15 mg / kg fase finalizadora). Os parâmetros de desempenho, ou seja, consumo de ração (FI), peso corporal vivo (PC) e FCR não foram significativamente (p > 0,05) afetados pela suplementação de selênio na fase inicial, mas foram significativamente (p < 0,05) afetados na fase final. A suplementação de selênio afetou significativamente (p < 0,05) o nível de Se sérico em diferentes grupos suplementados. O maior valor de Se sérico (58,20 ± 0,06) foi registrado no grupo D4. Da mesma forma, valor de selênio significativamente menor foi registrado para D4 e maior foi registrado para D1 (11,36 ± 0,08). No entanto, um valor mais baixo de Paraoxonase (PON) sérica foi registrado para D4 (13,24 ± 0,01) e mais alto para D1 (13,33 ± 0,03). A levedura enriquecida com Se comparativamente autodesenvolvida aumentou o acúmulo de Se e melhorou o sistema antioxidante. A glutationa peroxidase (GPx) foi encontrada maior em D4 (12,333 ± 0,03) seguido por D3, D2 e ​​D1 respectivamente. Enquanto a superóxido dismutase (SOD) foi significativamente menor (p < 0,05) em D4 (0,1437 ± 0,003) seguido por D3 (0,1457 ± 0,002). A suplementação de selênio aumentou a taxa de sobrevivência da ave. Aves alimentadas com levedura enriquecida com Se apresentaram maior deposição de Se e melhor capacidade antioxidante em comparação com outras fontes de selênio. A levedura enriquecida com Se apresentou um resultado melhorado na deposição de Se nos tecidos, capacidade oxidativa, maciez da carne e nível de resposta imune em comparação com outras fontes de selênio.

Bilateral Primary Adrenal B-Cell Lymphoma Diagnosed by Workup for Primary Adrenal Deficiency.

Primary adrenal lymphoma (PAL) often occurs bilaterally and is a rare malignancy of old age. Workup for primary adrenal insufficiency often unmasks this underlying grave pathology. In this article, we present a case of a 73-yearold patient who presented with features of primary adrenal insufficiency and renal colic. Diagnostic abdominal imaging revealed bilateral suprarenal masses as the cause of adrenal gland destruction and the patient's symptoms. FDG PET-CT scan and histopathology confirmed the diagnosis of mature bilateral B-cell primary adrenal lymphomas. Though the patient showed an excellent initial response to the first four chemotherapy cycles, a relapse resulted in metastatic disease. This article highlights the PAL's disease course, imaging features, and management dilemma due to Chemotherapy's side effects and a higher recurrence rate. Keywords: Primary adrenal lymphoma, Primary adrenal insufficiency, R-CHOP, Role of imaging.

Edema of the Ligamentum Teres as a Novel MRI Marker for Non-Traumatic Painful Hip Pathology: A Retrospective Observational Study.

Background The ligamentum teres has been recognized as an important stabilizer of the hip joint and can be affected by various hip pathologies. This study aims to introduce ligamentum teres edema as an MRI marker to diagnose the underlying cause of hip pathology, mainly femoral acetabular impingement (FAI) and adult developmental dysplasia of the hip (ADDH), in non-traumatic patients. Methodology Adult patients presenting with non-traumatic hip pain of variable duration and ligamentum teres edema on MRI between 2014 and 2020 were included. A high-resolution standard MRI hip protocol was used for all patients in this series. MRI and plain radiographs were assessed. Ligamentum teres edema, alpha angle, center edge angle of Wiberg, and retroversion were assessed. Results In total, 55 patients with 110 hip joints (males: 29 (52.7%), females: 26 (47.3%)) of different ethnicities were included in this study. Out of the 55 patients with ligamentum teres edema, one had only unilateral right-sided FAI, seven had only unilateral left-sided FAI, and 46 (94 hip joints) had either bilateral FAI or ADDH. Therefore, eight (14.5%) patients with unilateral FAI had the absence of the contralateral FAI or ADDH (6.5% false-positive) despite the presence of ligamentum teres edema bilaterally, and the rest of the patients with bilateral ligamentum teres edema (102 joints: 92.7% positive predictive value) had findings of either FAI or ADDH. Conclusions Ligamentum teres edema can be considered as an early MRI marker to diagnose the underlying pathology of symptomatic painful hip disorders, especially FAI.

Loss of methylthioadenosine phosphorylase and elevated ornithine decarboxylase is common in pancreatic cancer.

PURPOSE: Loss of the methylthioadenosine phosphorylase (MTAP) gene at 9p21 is observed frequently in a variety of human cancers. We have shown previously that MTAP can act as a tumor suppressor gene and that its tumor suppressor function is related to its effect on polyamine homeostasis. Ornithine decarboxylase is a key enzyme in the regulation of polyamine metabolism. The aim of this study is to analyze MTAP and ornithine decarboxylase (ODC) expression in primary pancreatic tumor specimens. EXPERIMENTAL DESIGN: We measured MTAP and ODC activity in protein extracts derived from 30 surgically resected tumor samples and eight normal pancreas samples. In a subset of six samples, we also examined MTAP DNA using interphase fluorescence in situ hybridization. In addition, we examined the effect of the ODC inhibitor difluoromethylornithine on two pancreatic adenocarcinoma-derived cell lines. RESULT: MTAP activity was 2.8-fold reduced in adenocarcinomas and 6.3-fold reduced in neuroendocrine tumors compared with control pancreas. Conversely, ODC activity was 3.6-fold elevated in adenocarcinomas and 3.9-fold elevated in neuroendocrine tumors compared with control pancreas. Using interphase fluorescence in situ hybridization, we found in tumor samples that 43 to 75% of the nuclei had lost at least one copy of MTAP locus, indicating that loss of MTAP activity was at least partially because of deletion of the MTAP locus. We also show that inhibition of ODC by difluoromethylornithine caused decreased cell growth and increased apoptosis in two MTAP-deleted pancreatic adenocarcinoma-derived cell lines. CONCLUSIONS: MTAP activity is frequently lost, and ODC activity is frequently elevated in both pancreatic adenocarcinoma and neuroendocrine tumors. Inhibition of ODC activity caused decreased cell growth and increased apoptosis in pancreatic tumor-derived cell lines. These findings suggest that MTAP and polyamine metabolism could be potential therapeutic targets in the treatment of pancreatic cancer.

Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites.

The gene encoding methylthioadenosine phosphorylase (MTAP), the initial enzyme in the methionine salvage pathway, is deleted in a variety of human tumors and acts as a tumor suppressor gene in cell culture (Christopher, S. A., Diegelman, P., Porter, C. W., and Kruger, W. D. (2002) Cancer Res. 62, 6639-6644). Overexpression of the polyamine biosynthetic enzyme ornithine decarboxylase (ODC) is frequently observed in tumors and has been shown to be tumorigenic in vitro and in vivo. In this paper, we demonstrate a novel regulatory pathway in which the methionine salvage pathway products inhibit ODC activity. We show that in Saccharomyces cerevisiae the MEU1 gene encodes MTAP and that Meu1delta cells have an 8-fold increase in ODC activity, resulting in large elevations in polyamine pools. Mutations in putative salvage pathway genes downstream of MTAP also cause elevated ODC activity and elevated polyamines. The addition of the penultimate salvage pathway compound 4-methylthio-2-oxobutanoic acid represses ODC levels in both MTAP-deleted yeast and human tumor cell lines, indicating that 4-methylthio-2-oxobutanoic acid acts as a negative regulator of polyamine biosynthesis. Expression of MTAP in MTAP-deleted MCF-7 breast adenocarcinoma cells results in a significant reduction of ODC activity and reduction in polyamine levels. Taken together, our results show that products of the methionine salvage pathway regulate polyamine biosynthesis and suggest that MTAP deletion may lead to ODC activation in human tumors.

Pregnancy and murine thyroiditis: thyroglobulin immunization leads to fetal loss in specific allogeneic pregnancies.

Thyroid autoantibodies are risk factors in human pregnancy. To investigate the influence of autoimmune thyroiditis on pregnancy, we have studied the impact of murine experimental autoimmune thyroiditis (EAT) on pregnancy outcome by using thyroglobulin (Tg) immunized CBA/J (H2(k)) female mice. When Tg immunized mice were mated with BALB/c (H2(d)) males, only 57% (47/83) of pregnant mice maintained their conceptions compared with >85% of other strain combinations (P < 0.05). We also found that MHC class II antigens were expressed on placental cells from Tg immunized pregnant mice but not in control normal pregnancies. Furthermore, the frequency and severity of thyroiditis, assessed by histological analyses, was also increased in Tg immunized mice mated with the BALB/c strain compared with syngeneic pregnancies (P < 0.05). In these pregnant mice mated with BALB/c, interleukin-4 secretion by mitogen-stimulated spleen cells was significantly suppressed and interferon-gamma secretion by mixed lymphocyte reactions with BALB/c cells was significantly increased. These data demonstrated enhanced Th1 cell proliferation and fetal loss in CBA/J X BALB/c pregnancies. We concluded, therefore, that pregnancy loss was increased in experimental autoimmune thyroiditis in a manner that was dependent on paternal antigens. These observations have broad implications for understanding the immunology of pregnancy.

Non-MHC driven exacerbation of experimental thyroiditis in the postpartum period.

Many human autoimmune diseases, including those of the thyroid gland, are affected by immune changes during pregnancy and the postpartum period. To investigate this influence, we have developed an animal model of pregnancy thyroiditis by using thyroglobulin (Tg)-induced experimental autoimmune thyroiditis (EAT). We now report a study of the post-partum period in mice with EAT. At 5 weeks postpartum, which was 9 weeks after the completion of a Tg immunization regime, the mean thyroiditis grade was significantly increased in the postpartum group from 0.23 to 0.43 (p<0.05) and the thyroiditis Index, which reflected both the frequency and severity of thyroiditis, was similarly increased compared to controls (29.0 vs 9.0). When Tg immunized CBA/J (H-2k) female mice were mated with BALB/c (H-2d) males, there was a similar increase in the severity of thyroiditis in the postpartum period as seen with CBA/J males suggesting that allogeneic factors were not able to further this postpartum exacerbation. Spleen cell IL-4 secretion was enhanced in the postpartum but only in the presence of thyroiditis indicating enhanced activity of Th2 immune responses. There were no differences in IFN-gamma secretion, titers of anti-Tg, CD8+ & CD4+ T cells and T cell chemokine receptor (CCR5, CCR3) expression between non-pregnant control mice with thyroiditis and postpartum thyroiditis. In summary, we found that the severity of EAT during the postpartum was significantly greater than in non-pregnant control mice and was associated with enhanced Th2 immune responses. The allogenicity of the pregnancy had no influence on these findings. The lack of allogenic impact was in contrast to earlier observations in pregnancy itself where an exacerbation of thyroiditis was male strain-dependent and involved primarily Th1 responses. This indicated that the postpartum exacerbation of autoimmune thyroid disease was not a simple response to fetal antigens but secondary to unique postpartum factors.

The novel 5-Hydroxytryptamine(1A) antagonist LY426965: effects on nicotine withdrawal and interactions with fluoxetine.

LY426965 [(2S)-(+)-1-cyclohexyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]2-methyl- 2-phenyl-1-butanone monohydrochloride] is a novel compound with high affinity for the cloned human 5-hydroxytryptamine (HT)(1A) receptor (K(i) = 4.66 nM) and 20-fold or greater selectivity over other serotonin and nonserotonin receptor subtypes. Both in vitro and in vivo studies indicate that LY426965 is a full antagonist and has no partial agonist properties. LY426965 did not stimulate [(35)S]guanosine-5'-O-(3-thio) triphosphate (GTPgammaS) binding to homogenates of cells expressing the cloned human 5-HT(1A) receptor in vitro but did inhibit 300 nM 5-HT-stimulated [(35)S]GTPgammaS binding with a K(i) value of 3.07 nM. After both p.o. and s.c. administration, LY426965 blocked the lower lip retraction, flat body posture, hypothermia, and increase in rat serum corticosterone induced by the 5-HT(1A) agonist 8-OH-DPAT (8-hydroxy-2-dipropylaminotetralin). In pigeons, LY426965 dose-dependently blocked the stimulus cue induced by 8-OH-DPAT but had no 8-OH-DPAT-like discriminative properties. LY426965 completely reversed the effects of nicotine withdrawal on the auditory startle reflex in rats. In microdialysis experiments, LY426965 administered together with fluoxetine significantly increased extracellular levels of serotonin above those achievable with fluoxetine alone. In electrophysiological studies, the administration of LY426965 produced a slight elevation of the firing rate of 5-HT neurons in the dorsal raphe nucleus of anesthetized rats and both blocked and reversed the effects of fluoxetine on 5-HT neuronal activity. These preclinical results indicate that LY426965 is a selective, full 5-HT(1A) antagonist that may have clinical use as pharmacotherapy for smoking cessation and depression and related disorders.

Interleukin-6 levels are not increased in women with postpartum thyroid dysfunction.

Postpartum thyroid dysfunction (PPTD) is an autoimmune-mediated thyroid destructive process. Human interleukin-6 (IL-6) is a cytokine found to be increased in subacute thyroiditis, amiodarone-induced thyrotoxicosis, Graves' disease, and other thyroid destructive processes. We report serum IL-6 levels in PPTD in two independent studies. New York Study: In a previous prospective study we demonstrated that PPTD occurred in 25% (7/28) of women with type 1 diabetes mellitus. IL-6 determinations were made on the frozen serum samples of these 28 women during each trimester of their pregnancy and at 1.5, 3, 6, 9, and 12 months postpartum. IL-6 levels were found to be similar in women with PPTD compared with women without PPTD (mean 3.06+/-2.25 vs. 2.51+/-2.21 pg/mL; p = 0.15). No difference in IL-6 levels was found between the pre- and the postpartum periods (mean 2.67+/-1.82 vs. 3.04+/-2.44 pg/mL; p = 0.30) in all 28 women. Cardiff Study: Serum IL-6 levels were measured on frozen serum samples of 30 women with PPTD. IL-6 levels were below the detection limit (25 fmol/L or 0.65 pg/mL) in 94 (67%) of these samples. No significant difference in the mean serum IL-6 levels were found between any time points in the study. There was no correlation between serum IL-6 levels, thyroid peroxidase (TPO)- antibodies and serum thyrotropin (TSH) levels at any time point. IL-6 levels during pregnancy or postpartum were not found to be significantly different in women with PPTD compared with women without PPTD.

Presence of alkaline-phosphatase-positive reticulum cells in fetal liver and bone marrow of mice and their absence in yolk sac.

One of the conspicuous stromal cells in hematopoietic parenchyma of the bone marrow in adult mice is the alkaline-phosphatase-positive reticulum cell (A1-RC). To determine whether it is present in the fetal yolk sac, liver, and bone marrow of mice, these tissues were examined at the gestational ages when they are sites of hematopoiesis. Fetuses of nine, 16 and 18 days of gestation were fixed and embedded in plastic, and 2-micron sections were stained for alkaline phosphatase and examined by light microscopy. No cells with the characteristics of the A1-RC were seen in the blood islands of the yolk sac, the site of erythropoiesis. Because of the high resolution of this method, however, alkaline phosphatase activity was observed on the border of the adjacent endodermal cells for the first time. By 16 days, the liver contained A1-RC interspersed with hematopoietic cells, as well as alkaline phosphatase activity in bile canaliculi. We found that the A1-RC is the predominant stromal cell of bone marrow at 18 days of gestation. We conclude that, as maturation proceeds, the hematopoietic stromal environment becomes more similar to that of the adult.