A case of Takayasu disease with findings of incomplete Alagille syndrome

A 16-year-old girl being followed up for Takayasu arteritis for the last 3 years was also found to have Alagille syndrome upon findings of atypical facies, posterior embryotoxon, high-pitched voice, osteopenia and hypogonadism. This case might imply a possible relationship between Takayasu arteritis and Alagille syndrome.     

Acquired von Willebrand factor abnormalities in myeloproliferative disorders and other hematologic diseases: a retrospective analysis by a single institution

BACKGROUND AND OBJECTIVES. Acquired von Willebrand syndrome (AVWS) is a rare acquired disorder. In most cases it is associated with lymphoproliferative disorders and monoclonal gammopathies, while less frequently myeloproliferative disorders (MPD) are involved. Although bleeding is the most important symptom, thrombotic complications have also been observed in cases associated with MPD. Our aim was to review the clinical and laboratory findings in AVWS patients from a single institution. DESIGN AND METHODS. The records of 99 patients with AVWS were reviewed to identify the underlying diseases, the symptoms and the laboratory parameters. RESULTS. In 75% of cases the AVWS was associated with MPD. The most frequent pattern was type 2 (67.7%). Abnormalities of bleeding time, factor VIII levels or platelet retention to glass beads were observed in 83.8% of cases. Bleeding was present in 38.4% of patients, more frequently in the not-MPD-associated (58.3%) vs. MPD-associated cases (32%) (p=0.022), with a significant predominance in females, irrespective of the underlying disease (p=0.0007). In 32% of patients with MPD, thrombotic manifestations, mostly microvascular and arterial episodes, were observed. INTERPRETATION AND CONCLUSIONS. AVWS in MPD seems to be mainly a laboratory diagnosis, without clinical symptoms in most cases, although bleeding as well as ischemic events can be present. In contrast, AVWS in not-MPD-associated cases is most frequently associated with severe bleeding symptoms. Performing appropriate laboratory tests may be useful for screening for AVWS.     

Maternal preeclampsia and jitteriness in preterm infants

AIM: To clarify the role of maternal preeclampsia in jitteriness in preterm infants. METHODS: Sixteen premature infants of preeclamptic mothers were observed for occurrence of jitteriness and were compared with 32 premature infants born to normotensive women. RESULTS: Jitteriness was present in a significantly higher percentage (75 vs 6%) and persisted longer (4.5 +/- 5.6 vs 1.5 +/- 0.7 days) in the preterm infants of preeclamptic mothers. CONCLUSIONS: Maternal preeclampsia could be included among the pathological factors that cause jitteriness in preterm babies.     

Plasticity in rat uterine sympathetic nerves: the role of TrkA and p75 nerve growth factor receptors

Uterine sympathetic innervation undergoes profound remodelling in response to physiological and experimental changes in the circulating levels of sex hormones. It is not known, however, whether this plasticity results from changes in the innervating neurons, the neuritogenic properties of the target tissue or both. Using densitometric immunohistochemistry, we analysed the effects of prepubertal chronic oestrogen treatment (three subcutaneous injections of 20 microg of beta-oestradiol 17-cypionate on days 25, 27 and 29 after birth), natural peripubertal transition and late pregnancy (19-20 days post coitum) on the levels of TrkA and p75 nerve growth factor receptors in uterine-projecting sympathetic neurons of the thoraco-lumbar paravertebral sympathetic chain (T7-L2) identified using the retrograde tracer Fluorogold. For comparative purposes, levels of TrkA and p75 were assessed in the superior cervical ganglion (SCG) following prepubertal chronic oestrogen treatment. These studies showed that the vast majority of uterine-projecting neurons expressed both TrkA and p75. Both prepubertal chronic oestrogen treatment and the peripubertal transition increased the ratio p75 to TrkA in uterine-projecting neurons, whereas pregnancy elicited the opposite effect. Prepubertal chronic oestrogen treatment had no effects on levels of TrkA or p75 in sympathetic neurons of the SCG. Taken together, our data suggest that neurotrophin receptor-mediated events may contribute to regulate sex hormone-induced plasticity in uterine sympathetic nerves, and are in line with the idea that, in vivo, plasticity in uterine nerves involves changes in both the target and the innervating neurons.     

Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants

BACKGROUND: It has been shown that leptin is present in breast milk and human mammary epithelial cells are able to synthesize leptin. It has been suggested that leptin in human milk might be involved in the regulation of postnatal nutrition and growth. AIMS: To investigate whether there is a relationship between leptin levels in human milk and weight gain in the postnatal period and to compare variations of milk-borne maternal leptin concentrations for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) infants. INFANTS AND METHODS: Forty-seven healthy lactating women aged from 17-38 years and their infants were included in the study. The infants were separated into three groups according to birth weight as SGA (n = 11), LGA (n = 14) and AGA (n = 22). All infants were fed with breast milk during the study period. Anthropometric measurements were performed on the 15th day of life and at 1, 2, and 3 months of age, and the body mass index (BMI) of the infants' mothers was calculated. Breast milk leptin levels were analyzed by radioimmunoassay. RESULTS: Breast milk leptin levels were found reduced in the SGA group and increased in the LGA group compared to the AGA group at 15 days of life (13.4 +/- 2.2, 28.5 +/- 4.4 and 18.4 +/- 2 ng/ml, respectively; p <0.05). At 1 month of age, leptin levels in breast milk were significantly lower in the LGA group than in the AGA group (15.5 +/- 4.9, 19.4 +/- 1.7 ng/ml, respectively; p<0.05). There was no difference among the three groups at 2 and 3 months of age (p>0.05). There was a positive correlation between birth Weight and breast milk leptin levels on the 15th day (r = 0.47, p = 0.001). A negative correlation was found between weight gain during the first 15 days and 1 month of life and breast milk leptin levels on the 15th day (r = -0.44, p = 0.002; r = -0.40, p = 0.005, respectively). No relationship could be determined between breast milk leptin levels and BMI of the mothers. CONCLUSION: Maternal milk of SGA, LGA and AGA infants had different leptin levels, especially during the first month of life. More rapid growth was shown in the SGA infants during the first postnatal 15 days compared to AGA and LGA infants, and human milk leptin levels were significantly reduced in the SGA group. However, LGA infants gained more weight during the second 15 days of life and breast milk leptin levels were dramatically decreased in LGA and increased in SGA infants at the end of first month of life. These findings suggest that the presence of leptin in breast milk might have a significant role in growth, appetite and regulation of nutrition in infancy, especially during the early lactation period, and the production of leptin in breast tissue by human mammary epithelial cells might be regulated physiologically according to necessity and state of the infant.     

Sustained exposure to bacterial antigen induces interferon-gamma-dependent T cell receptor zeta down-regulation and impaired T cell function

T cell antigen receptor zeta chain down-regulation and impaired in vitro T cell function have been described in cancer and autoimmune and infectious diseases. However, the immunological basis for this phenomenon is unknown. Sustained exposure to antigen and chronic systemic inflammation, factors shared by the various pathologies, might account for this phenomenon. We developed an in vivo experimental system that mimics these conditions and show that sustained exposure of mice to bacterial antigens was sufficient to induce T cell antigen receptor zeta chain down-regulation and impair T cell function, provided an interferon-gamma-dependent T helper type 1 immune response developed. This indicates zeta chain down-regulation could be a physiological response that attenuates an exacerbated immune response. However, it can act as a 'double-edged sword', impairing immune responses to chronic diseases.     

Transient tear hyperosmolarity disrupts the neuroimmune homeostasis of the ocular surface and facilitates dry eye onset

Dry eye disease (DED) is a highly prevalent ocular surface disorder with neuroimmune pathophysiology. Tear hyperosmolarity (THO), a frequent finding in affected patients, is considered a key element in DED pathogenesis, yet existing animal models are based on subjecting the ocular surface to the more complex desiccating stress − decreased tear production and/or increased evaporation − instead of strict hyperosmolar stress. Here we characterized a murine model of THO that does not involve desiccating stress, thus allowing us to dissect the contribution of THO to DED. Our results showed that THO is sufficient to disrupt neuroimmune homeostasis of the ocular surface in mice, and thus reproduce many sub-clinical DED findings. THO activated nuclear factor-κB signalling in conjunctival epithelial cells and increased dendritic cell recruitment and maturation, leading to more activated (CD69⁺) and memory (CD62lo CD44hi) CD4⁺ T-cells in the eye-draining lymph nodes. Ultimately, THO impaired the development of ocular mucosal tolerance to a topical surrogate antigen in a chain of events that included epithelial nuclear factor-κB signalling and activation of transient receptor potential vanilloid 1 as the probable hypertonicity sensor. Also, THO reduced the density of corneal intraepithelial nerves and terminals, and sensitized the ocular surface to hypertonicity. Finally, the adoptive transfer of T-cells from THO mice to naïve recipients under mild desiccating stress favoured DED development, showing that THO is enough to trigger an actual pathogenic T-cell response. Our results altogether demonstrate that THO is a critical initiating factor in DED development.