Miscarriage, and TNF-α and osteopontin relationship in women patients with Hashimoto's thyroiditis

Objective: Infertility and reproductive impairment can be compromised by abnormalities in both endocrine and immune system. TNF-α promotes apoptotic cell death in fetal membrane tissues and pro-inflammatory, proapoptotic, and procoagulant properties of TNF-α probably contribute to widely accepted abortogenic profile of this cytokine. The aim of this study was to assess the alteration in the levels of TSH, FT3, FT4, TNF-α, osteopontin in pregnant and controls. Methods: Study subjects were 28 pregnant women, 28 non-pregnant women, and 28 healthy controls. All subjects underwent venous blood drawing for levels of TNF-α, osteopontin, and also hormonal assays including the levels of anti-TPO, anti-TG antibodies, TSH, FT3, FT4. Results: Both patient and control groups are similar in terms of age. Pregnancy age in conceived patients is 23.64 ± 2.040. No statistically meaningful relation was found in correlation analysis between TNF-α and osteopontin among the groups (p = 0.963). Anti-thyroglobuline antibody and anti-microsomal antibody levels were found to be higher in patients with non-pregnant patients with Hashimoto thyroiditis than the control group (p < 0.001). No statistically meaningful relation was found in terms of TNF-α (p = 0.66) and osteopontin serum levels (p = 0.50) in patient groups with or without miscarriage history. Conclusions: In our study, no statistically meaningful relation was found in terms of TNF-α and osteopontin serum levels in patient groups with and without miscarriage history.     

The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation

The CSF-1 receptor (CSF-1R) regulates CNS microglial development. However, the localization and developmental roles of this receptor and its ligands, IL-34 and CSF-1, in the brain are poorly understood. Here we show that compared to wild type mice, CSF-1R-deficient (Csf1r-/-) mice have smaller brains of greater mass. They further exhibit an expansion of lateral ventricle size, an atrophy of the olfactory bulb and a failure of midline crossing of callosal axons. In brain, IL-34 exhibited a broader regional expression than CSF-1, mostly without overlap. Expression of IL-34, CSF-1 and the CSF-1R were maximal during early postnatal development. However, in contrast to the expression of its ligands, CSF-1R expression was very low in adult brain. Postnatal neocortical expression showed that CSF-1 was expressed in layer VI, whereas IL-34 was expressed in the meninges and layers II-V. The broader expression of IL-34 is consistent with its previously implicated role in microglial development. The differential expression of CSF-1R ligands, with respect to CSF-1R expression, could reflect their CSF-1R-independent signaling. Csf1r-/- mice displayed increased proliferation and apoptosis of neocortical progenitors and reduced differentiation of specific excitatory neuronal subtypes. Indeed, addition of CSF-1 or IL-34 to microglia-free, CSF-1R-expressing dorsal forebrain clonal cultures, suppressed progenitor self-renewal and enhanced neuronal differentiation. Consistent with a neural developmental role for the CSF-1R, ablation of the Csf1r gene in Nestin-positive neural progenitors led to a smaller brain size, an expanded neural progenitor pool and elevated cellular apoptosis in cortical forebrain. Thus our results also indicate novel roles for the CSF-1R in the regulation of corticogenesis.     

Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke

Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.     

The use of gating technology in bioengineering insulin-secreting cells from embryonic stem cells

Embryonic stem cells display the ability to differentiate in vitro into a variety of cell types. This process is induced by embryoid body formation, addition of several soluble growth factors to the culture medium and other strategies. However, none of the used factors is capable to drive differentiation to only one specific celltype. The use of gating technology has allowed to partially overcome this problem. The rational behind this technique is based on the transfection of stem cells with a transgene carrying expression cassettes for a cell type specific promoter, regulating expression ofa selectable marker to select one cell lineage from other cell lineages.Using this system, we have obtained insulin-secreting cells by transfecting mouse embryonic stem cells with a DNA construct providing resistance to neomycin under the control of the regulatory regions of the human insulin gene. Furthermore, gating technology has been successfully used to isolate other cell types such as cardiomyocytes and neural precursors from undifferentiated embryonic stem cells. This review focuses on the possibilities offered by this technology in embryonic stem cell bioengineering, mainly to obtain insulin-secreting cells. Advantages and considerations of this selection system will be also discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Multicomponent pattern and biological activities of seven Asphodeline taxa: potential sources of natural-functional ingredients for bioactive formulations

The current study was carried out to evaluate multicomponent pattern, biological and enzymatic activities of seven Asphodeline taxa root extracts as useful ingredients, due to the fact that these plants are commonly used as traditional food supplements in Turkish regions. The extracts were characterized for free anthraquinones and phenolics to obtain a specific chemical fingerprint useful for quality control. These analyzes were coupled to biological and enzymatic activities in order to obtain comprehensive information of the natural product. Free anthraquinones and phenolics were determined using validated HPLC-PDA methods. Antioxidant properties were determined by different procedures including free radical scavenging, reducing power, phosphomolybdenum and metal chelating assays. Ames assay was performed to evaluate mutagenic/antimutagenic properties. Enzyme inhibitory activities were tested against cholinesterase, tyrosinase, α-amylase and α-glucosidase. From the herein reported results, Asphodeline could be valuable for the production of bioactive products or food supplements for cosmetic and pharmaceutical industries.     

Unilateral hysterectomy (cornuectomy) in the bitch and its effect on subsequent fertility

During caesarean section of bitches a beginning tissue necrosis of the uterus is often encountered. These alterations mostly require ovariohysterectomy that means the end of breeding life. The aim of this study was to create a model for unilateral hysterectomy during dystocia and to evaluate subsequent fertility. Unilateral cornuectomy was performed in 18 clinically healthy bitches of different ages, breeds, and at different stages of the sexual cyclus. Four bitches were not available for follow-up examinations. Twelve bitches were mated at the first obvious estrus period postoperatively and 10 pregnancies were diagnosed. Nine bitches delivered one to five puppies (mean 3.8) after a gestation period of 63-67 days. The puppies (n=38) were in a very good condition and showed high vitality. Unilateral cornuectomy of the uterus had no adverse effects and postoperative mating revealed pregnancy without complications and normal parturition. In the case of pathological changes in one uterine horn during a caesarean section unilateral hysterectomy seems to be an alternative to ovariohysterectomy.     

A life-threatening multilocalized hidradenitis suppurativa case

The patient was a 38-year-old man. He had been suffering from hidradenitis suppurativa (HS) for approximately 20 years. He had active lesions at both axillas, hip, scrotum, and perineum, and inactive lesions located behind the ears, lower abdomen, and posterior neck. He was monitored and treated at different branches; he continuously used antibiotics and was given steroids at times. Antibiotic resistance developed subsequently. His general situation was bad; vital signs were poor; and he was in a state of sepsis and preshock, so this case was regarded as life-threatening. Total excision was performed first on the lesion at the right axilla, then on the lesion at the left axilla, and the parascapular fasciocutaneous flap was reversed. A skin graft was applied to the triangular defect on the scapula. No relapse occurred. Then the lesions at the hip were managed. Broad excision was used twice with the patient under general anesthesia; because the lesions spread to the retrococcygeal and gluteal muscles, coccyx resection and partial gluteal muscle resection were implemented. The defect was eliminated with a progressive flap. At the intergluteal sulcus, small lesions emerging at the median line were debrided with the patient under local anesthesia, and together with secondary recovery, the disease was completely managed. Lesions at the perineum and scrotum and at both inguinal areas were broadly excised and grafted. No lesion has relapsed so far. One year later, Hodgkin's lymphoma was diagnosed, and the patient was treated with chemoradiotherapy easily, because there was no infective focus. The disease is in remission now. The patient weighs 110 kg, is healthy, and is working again.