Multi-aspect testing and ranking inference to quantify dimorphism in the cytoarchitecture of cerebellum of male, female and intersex individuals: a model applied to bovine brains.

The dimorphism among male, female and freemartin intersex bovines, focusing on the vermal lobules VIII and IX, was analyzed using a novel data analytics approach to quantify morphometric differences in the cytoarchitecture of digitalized sections of the cerebellum. This methodology consists of multivariate and multi-aspect testing for cytoarchitecture-ranking, based on neuronal cell complexity among populations defined by factors, such as sex, age or pathology. In this context, we computed a set of shape descriptors of the neural cell morphology, categorized them into three domains named size, regularity and density, respectively. The output and results of our methodology are multivariate in nature, allowing an in-depth analysis of the cytoarchitectonic organization and morphology of cells. Interestingly, the Purkinje neurons and the underlying granule cells revealed the same morphological pattern: female possessed larger, denser and more irregular neurons than males. In the Freemartin, Purkinje neurons showed an intermediate setting between males and females, while the granule cells were the largest, most regular and dense. This methodology could be a powerful instrument to carry out morphometric analysis providing robust bases for objective tissue screening, especially in the field of neurodegenerative pathologies.

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics.

A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.

[Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics]. / Polimorfismo del gen de aldosa reductasa y velocidad de aparición de retinopatía en diabéticos no insulinodependientes.

BACKGROUND: Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. AIM: To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. PATIENTS AND METHODS: A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. RESULTS: Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. CONCLUSIONS: Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.