Alterations in the insulin-like growth factor system during the menstrual cycle in normal women

Objectives: To evaluate the effects of endogenous estrogens and progestins on the IGF-system during the normal menstrual cycle in healthy premenopausal women not using contraceptive drugs. Methods: Nine women had fasting blood samples obtained at 2–3 days intervals during a 5 week study period. Plasma levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3, estradiol and progesterone were measured by radioimmunoassay (RIA) in each sample. IGFBP-3 was also evaluated by Western ligand blot (WLB) and immunoblot. Any differences between the menstrual phase (defined as day 1–5), follicular and luteal phases (separation based on plasma estradiol and progesterone values) were evaluated by the Friedman test. Results: A small but significant difference in plasma levels of IGF-I (P<0.01) and IGFBP-3 (P<0.05) measured by RIA between the three phases were seen with the highest levels found during the follicular phase. No change in plasma levels of IGFBP-1 and IGF-II was found and immunoblots did not reveal any alteration in the ratio of fragmented to intact IGFBP-3 during the menstrual cycle. A positive correlation between plasma levels of IGF-I and estradiol was seen in 8 out of 9 patients (P=0.012). Conclusions: The finding of a slight but significant higher level of plasma IGF-I in the follicular and luteal phases compared with the menstrual phase suggests plasma estradiol may influence the level of this growth factor. This hypothesis is further supported by the finding of a correlation between plasma levels of IGF-I and estradiol but not progesterone in individual patients at different times during the menstrual cycle.     

Experimental Lead Neuropathy: Ultrastructural And Molecular Changes In The Rat Sciatic Nerve

Experimental lead intoxication is an important model for the study of cellular and molecular mechanisms of segmental demyelination in peripheral nerve. In this report we have compared pathological changes with the molecular and immunohistochemical expression of the proteins of compact and non-compact myelin in the demyelinating neuropathy induced in Sprague-Dawley rats after chronic administration (3 and 6 months) of lead acetate in drinking water. All the rats underwent the neurophysiological determination of the conduction velocity in the tail nerve at baseline and 3, 4.5 and 6 months after the beginning of the lead acetate administration. At the end of the treatment period the rats were sacrificed and sciatic nerve specimens were obtained. The neurophysiological study demonstrated a significant decrease in the nerve conduction velocity, which was already evident at the first determination (3 months) and persisted along the entire experiment. The neurophysiological results were in agreement with the pathological observations performed in the sciatic nerve, where several large demyelinated fibers were observed in the lead-intoxicated rats. Northern and Western blot analysis demonstrated that steady state mRNA and protein levels for P0, MBP, PMP22 and PLP were not changed comparing treated and control rats. Immunohistochemistry on teased fibers revealed that those proteins were distributed in areas of compact myelin along the internodes. In control fibers, as expected, MAG was found in the periaxonal cytoplasm, at nodes of Ranvier, and in the Schmidt-Lanterman incisures. In lead neuropathy, MAG was still limited to discrete regions, but the intensity of staining was reduced, in accordance with changes of paranodal structures. Immunohistochemical localization of other proteins of non-compacted myelin, including connexin-32, E-cadherin and β-catenin was also examined. Our data further suggest that chronic lead intoxication in the rat produces segmental demyelination due primarily to Schwann cell dysfunction.     

静磁场暴露对于大鼠睾丸组织电学特性的影响

目的研究静磁场暴露对于大鼠睾丸组织介电特性与导电特性的影响,从细胞水平和分子水平分析静磁场对于大鼠睾丸组织的影响。方法在10 kHz～10 MHz范围内测量被1700 Gs静磁场暴露作用大鼠的睾丸组织的电容和电阻,并进一步通过测试结果计算其介电与导电特性。结果通过静磁场暴露作用的大鼠其睾丸组织的介电常数总体上呈现降低趋势,在第7天以后开始恢复,在频率较高时恢复的时间较早,其电导率的变化趋势则是先上升,在第5天以后开始下降,具有显著差异的结果主要集中在较低频率的10 kHz～100 kHz范围内。结论静磁场对于大鼠睾丸组织电学特性的显著的影响主要集中在细胞水平,对于分子水平的影响不显著,并且这些影响在一段时间后可以自行恢复。     

Food hypersensitivity and quality of life

PURPOSE OF REVIEW: The present article presents an accessible review of research results on food hypersensitivity and quality of life (QoL), including 15 original articles on the subject. RECENT FINDINGS: Research on food hypersensitivity and QoL covers children and their parents, adolescents and adults. Several domains of QoL are affected, such as family and social activities, emotional issues and family economy. Food-hypersensitive children are to a large extent limited in their autonomous social activities. Food-allergic adolescents have a higher number of weeks absent from school compared with a control group, and a relatively high percentage of food-allergic young adults do not participate in the labour market. Comorbidity has to be taken into consideration when assessing QoL in food-hypersensitive individuals. Research on gender differences in food hypersensitivity and QoL are scarce. SUMMARY: Although development in this research field has only just begun, it is obvious that food hypersensitivity has a significant impact on individuals' and families' QoL. An important advance is the disease-specific QoL measure instruments that have been created. There is still, however, a need for a more in-depth knowledge as a basis for further development of QoL instruments, and as a basis for societal interventions and family/individual support.     

Predictive value of Kushida index and acoustic pharyngometry for the evaluation of upper airway in subjects with or without obstructive sleep apnea

Acoustic pharyngometry is a relatively new noninvasive method that quantifies geometrically complexed pharyngeal dimensions. Our study aimed to investigate the predictability and usefulness of acoustic pharyngometry in diagnosis of obstructive sleep apnea (OSA), and we developed a prospective clinical trial in 16 subjects without apnea and 54 subjects with apnea. All seventy subjects received polysomnography (PSG) to assess the sleep architecture, including breathing and the degree of apnea hypopnea index. Acoustic pharyngometry was performed in four body positions (sitting, supine, right and left lateral) while awake with tidal breathing in addition to morphometric measurements (Kushida index) of oral cavity. This study shows that the cross-sectional area and volume of the upper airway is smaller in the supine position than any other positions. As well, the oropharyngeal junction area of the supine position is the most predictive parameter to discriminate between subjects with or without OSA. Acoustic pharyngometry can be a clinically useful tool for localizing the narrowed portion of the upper airway and predicting obstructive sleep apnea.     

Are animal models useful for understanding the pathophysiology of lysosomal storage disease?

Spontaneously occurring genetic lysosomal storage diseases are as rare in other mammalian species as in man. However, the advent of gene targeting technology has revolutionized the state of animal models of genetic diseases. Nearly all lysosomal storage diseases known in man have been duplicated in the mouse. The technology now allows, not only complete inactivation of endogenous genes, but also the introduction of essentially any type of mutation. These animal models can overcome many of the limitations inherent in studies of human patients - rarity of the disease, extremely complex genetic background and logistical and ethical constraints in the design and execution of experiments with human subjects. For example, genetic manipulations of germ cells or cross-breeding experiments between two mutants are readily feasible with animal models. Two major areas of the utility of animal models are the clarification of the pathophysiology/pathogenetic mechanism of disease and the exploration of therapeutic approaches. Examples of experiments using animal models of lysosomal storage disease are presented, primarily from studies undertaken in our own laboratory.
Conclusion : Animal models have proved invaluable in extending our knowledge of the lysosomal storage diseases and exploring potential therapies.