Prenatal Hypoxic-Ischemic Insult Changes the Distribution and Number of NADPH-Diaphorase Cells in the Cerebellum

Astrogliosis, oligodendroglial death and motor deficits have been observed in the offspring of female rats that had their uterine arteries clamped at the 18th gestational day. Since nitric oxide has important roles in several inflammatory and developmental events, here we evaluated NADPH-diaphorase (NADPH-d) distribution in the cerebellum of rats submitted to this hypoxia-ischemia (HI) model. At postnatal (P) day 9, Purkinje cells of SHAM and non-manipulated (NM) animals showed NADPH-d+ labeling both in the cell body and dendritic arborization in folia 1 to 8, while HI animals presented a weaker labeling in both cellular structures. NADPH-d+ labeling in the molecular (ML), and in both the external and internal granular layer, was unaffected by HI at this age. At P23, labeling in Purkinje cells was absent in all three groups. Ectopic NADPH-d+ cells in the ML of folia 1 to 4 and folium 10 were present exclusively in HI animals. This labeling pattern was maintained up to P90 in folium 10. In the cerebellar white matter (WM), at P9 and P23, microglial (ED1+) NADPH-d+ cells, were observed in all groups. At P23, only HI animals presented NADPH-d labeling in the cell body and processes of reactive astrocytes (GFAP+). At P9 and P23, the number of NADPH-d+ cells in the WM was higher in HI animals than in SHAM and NM ones. At P45 and at P90 no NADPH-d+ cells were observed in the WM of the three groups. Our results indicate that HI insults lead to long-lasting alterations in nitric oxide synthase expression in the cerebellum. Such alterations in cerebellar differentiation might explain, at least in part, the motor deficits that are commonly observed in this model

Wrist and palm indexes in carpal tunnel syndrome Índices de palma/punho e síndrome do túnel do carpo

According to median sensory latency > or = 3.7 ms (wrist-index finger [WIF], 14 cm), median/ulnar sensory latency difference to ring finger > or = 0.5 ms (14 cm) or median midpalm (8 cm) latency > or = 2.3 ms (all peak-measured), 141 Brazilian symptomatic patients (238 hands) have CTS confirmation. Wrist ratio (depth divided by width, WR) and a new wrist/palm ratio (wrist depth divided by the distance between distal wrist crease to the third digit metacarpophalangeal crease, WPR) were measured in all cases. Previous surgery/peripheral neuropathy were excluded; mean age 50.3 years; 90.8% female. Control subjects (486 hands) have mean age 43.0 years; 96.7% female. The mean WR in controls was 0.694 against 0.699, 0.703, 0.707 and 0.721 in CTS groups of progressive WIF severity. The mean WPR in controls was 0.374 against 0.376, 0.382, 0.387 and 0.403 in CTS groups of WIF progressive severity. Both were statistically significant for the last two groups (WIF > 4.4 ms, moderate, and, WIF unrecordable, severe). BMI increases togetherwith CTS severity and WR. It was concluded that both WR/WPR have a progressive correlation with the severity of CTS but with statistically significance only in groups moderate and severe. In these groups both WR and BMI have progressive increase and we believe that the latter could be a risk factor as important as important WR/WPR.<br>Um grupo de 141 pacientes (238 mãos) com síndrome do túnel do carpo (STC) sintomático foi estudado após confirmação por condução nervosa: latência distal sensitiva do nervo mediano (LDS-M) > ou = 3,7 ms (punho -- II dedo, 14 cm), diferença de latência sensitiva mediano-ulnar > ou = 0,5 ms (punho -- IV dedo, 14 cm) e/ou latência palma-punho do nervo mediano > ou = 2,3 ms (8 cm); as latências foram medidas no pico do potencial. Todos os casos tiveram as seguintes medidas calculadas: 1. Índice do punho (IP, espessura dividido pela largura do punho); 2. Índice punho-palma (IPP, espessura do punho dividido pela distância entre a prega distal do punho e a prega mais proximal do III dedo); a média de idade foi de 50,3 anos com 90,8% do gênero feminino. Foram realizadas mesmas medidas em 486 mãos do grupo controle (GC) cuja idade média foi 43,0 anos e 96,7% do gênero feminino. O IP médio do GC foi de 0,694 contra 0,699/0,703/0,707/0,721 do grupo STC (valores relativos a casos incipiente/leve/moderado/grave). O IPP médio do GC foi de 0,374 contra 0,376/0,382/0,387/0,403 do grupo STC. Ambos os índices apresentaram significância estatística na comparação com STC mais grave (moderado: LDS-M > 4,4 ms e grave: LDS-M não obtida). O índice de massa corporal aumentou de acordo com a gravidade do STC e o IP. Conclui-se que tanto o IP como o IPP apresentam correlação progressiva com a gravidade do STC porém com significância estatística apenas nos grupos moderado e grave. Neste grupos tanto o IP como o índice de massa corporal tiveram aumento progressivo e acreditamos que o último possa representar risco tão importante quanto IP/IPP

Allelic penetrance approach as a tool to model two-locus interaction in complex binary traits.

Many binary phenotypes do not follow a classical Mendelian inheritance pattern. Interaction between genetic and environmental factors is thought to contribute to the incomplete penetrance phenomena often observed in these complex binary traits. Several two-locus models for penetrance have been proposed to aid the genetic dissection of binary traits. Such models assume linear genetic effects of both loci in different mathematical scales of penetrance, resembling the analytical framework of quantitative traits. However, changes in phenotypic scale are difficult to envisage in binary traits and limited genetic interpretation is extractable from current modeling of penetrance. To overcome this limitation, we derived an allelic penetrance approach that attributes incomplete penetrance to the stochastic expression of the alleles controlling the phenotype, the genetic background and environmental factors. We applied this approach to formulate dominance and recessiveness in a single diallelic locus and to model different genetic mechanisms for the joint action of two diallelic loci. We fit the models to data on the genetic susceptibility of mice following infections with Listeria monocytogenes and Plasmodium berghei. These models gain in genetic interpretation, because they specify the alleles that are responsible for the genetic (inter)action and their genetic nature (dominant or recessive), and predict genotypic combinations determining the phenotype. Further, we show via computer simulations that the proposed models produce penetrance patterns not captured by traditional two-locus models. This approach provides a new analysis framework for dissecting mechanisms of interlocus joint action in binary traits using genetic crosses