The role of epsilon phenotype in brain glucose consumption in Alzheimer’s disease

The aim of our study was to investigate the impact of the epsilon phenotype in brain glucose consumption in a population with Alzheimer’s disease. Statistical Parametric Mapping (SPM8) was used to investigate differences in brain glucose consumption (as detectable by means of 18F FDG-PET/CT) in the population examined. A total of 129 patients (72 females and 57 males) with a diagnosis of probable AD according to the NINCDS-ADRDA criteria underwent the PET/CT examination. The mean (SD) age of the patients was 70 (± 7) years; the mean Mini-Mental State Examination was 19(± 5.6). 59 expressed epsilon 4 phenotype (E4) and 70 expressed the epsilon 3 phenotype (E3). Cerebral spinal fluid amyloid, tau, and t-tau have been measured resulting equal to 367.4 (± 149.1), 584.7 (± 312.1), and 79.2(± 45.9) pg/ml, respectively. Patients with confirmed amyloid and Tau changes were classified as AD. Patients with amyloid changes but negative Tau, considered as high risk of AD, were classified as IAD. Age, sex, MMSE, scholarship, and CSF parameters were used as a covariate in the SPM analyses. We did not find significant differences in age, gender, and MMSE and CSF parameters among groups. In the analysis of the AD group as compared to AD-E3, AD-E4 subjects show a significant reduction of brain glucose consumption in inferior frontal gyrus bilaterally (BA 45, BA 47). In the analysis of the IAD group as compared to IAD-E3, IAD-E4 subjects show a significant reduction of brain glucose consumption in right in medial, middle, and superior frontal gyrus (BA10, BA11), and in left medial and middle frontal gyrus (BA10, BA11). The differences between IAD-E3 and AD-E3 and between IAD-E4 and AD-E4 (and vice versa analysis) resulted not significant. APO-e4 is related to a major involvement of the frontal cortex confirming its role of risk factor in AD, while APO-3 seems not related to a specific pattern, supporting the hypothesis of neutral/protective role in AD.     

伴有LADD综合征的角膜缘干细胞缺乏

泪管-耳-牙-指（趾）（LADD）综合征是一种具有多种表现的常染色体显性遗传疾病。最初在1967年由Levy报道。1例双侧泪液系统缺失、杯状耳、干嘴，以及牙、手臂和指（趾）异常的单发病例。之后一些新发现的临床表现，如肾脏异常、唾液腺缺乏、先天性髋脱位、先天性裂孔疝和横膈疝、感觉性耳聋和传导性耳聋、牙发育不全、四肢异常、口腔干燥和眼干都被报道与此综合征有关。     

Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl.

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.     

Adequacies of skin puncture for evaluating biochemical and hematological blood parameters in athletes.

OBJECTIVE: The authors tested the effect of blood sampling (skin versus venous puncture) on some biochemical and hematological blood parameters in athletes to answer whether skin puncture could be used as a substitute for venous puncture. DESIGN: Comparative study of 2 methods of blood samples collection. SETTING: The blood was collected in the same athletes at 3 different moments of the preparatory training phase. PARTICIPANTS: Fourteen male indoor soccer players (22 +/- 1 years old) and 7 female handball players (18 +/- 1 years old) participated. MAIN OUTCOME MEASUREMENT: Blood was collected in heparin and K3EDTA by Vacutainer BD or Microvette Sarstedt system for biochemical and hematological analyses, respectively. RESULTS: There were no significant statistical differences between the 2 methods for the values of creatine kinase, urea, creatinine, lymphocytes, and platelets. The other hematological analyzes and uric acid exhibited significant higher values in skin blood, although they were all within the normal expected range. A high degree of correlation was observed between the 2 techniques for all parameters. CONCLUSIONS: Skin puncture is a reliable, easy, accurate, and less invasive sampling method for assessing hematological and some biochemical parameters in athletes, respecting that blood samples should always be obtained from the same site, especially in follow-up studies.     

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin.

Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma.